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Jeff Evans has been editor of Rheumatology News/MDedge Rheumatology and the EULAR Congress News since 2013. He started at Frontline Medical Communications in 2001 and was a reporter for 8 years before serving as editor of Clinical Neurology News and World Neurology, and briefly as editor of GI & Hepatology News. He graduated cum laude from Cornell University (New York) with a BA in biological sciences, concentrating in neurobiology and behavior.
Gout incidence is intertwined with serum urate, but only up to a point
SAN DIEGO – The incidence of gout is strongly linked to patients’ concentration of serum uric acid over time, but even so, less than half of patients with levels of 10 mg/dL or above develop the condition by 15 years, according to the largest individual person-level analysis to examine the relationship.
The incidence of gout rose from about 1% after 15 years in patients with a serum uric acid (sUA) level of less than 6 mg/dL to almost 49% in those with 10 mg/dL or higher in the study, which implies “a long period of hyperuricemia preceding the onset of clinical gout” and also “supports a role for additional factors in the pathogenesis of gout,” Nicola Dalbeth, MD, said in her presentation of the results at the annual meeting of the American College of Rheumatology.
Dr. Dalbeth and her associates found four studies in a search of PubMed and the Database of Genotype and Phenotype from Jan. 1, 1980, to June 11, 2016, that met the inclusion criteria of containing publicly available participant level data, recorded incident gout (via classification criteria, doctor’s diagnosis, or self report of disease), and had a minimum of 3 years of follow-up. The four studies were the Atherosclerosis Risk in Communities study, the Coronary Artery Risk Development in Young Adults study, the original cohort of the Framingham Heart Study, and the offspring cohort of the Framingham Heart Study, comprising 18,889 individuals who were gout free at the beginning of follow-up, which lasted a mean of 11.2 years.
In all studies combined, the incidence of gout at an sUA level of less than 6 mg/dL steadily increased from 0.21% at 3 years of follow-up to 1.12% at 15 years. In contrast, sUA at 10 mg/dL or higher led to gout in 10.00% at 3 years and in 48.57% at 15 years.
The same general pattern held for the incidence of gout in both men and women, although men had a higher incidence across nearly all sUA concentration ranges.
Female sex provided a 30% reduced risk of gout, and European ethnicity nearly halved the risk for gout, compared with non-Europeans, The risk for gout rose across decades of age, starting at 40-49 years, and also increased significantly for each 1-mg/dL interval of sUA starting at 6 mg/dL.
The study’s conclusions are limited by the use of variable definitions of gout and how it was ascertained. In addition, the study did not analyze other endpoints that are associated with hyperuricemia and may be relevant to discuss in counseling people with elevated sUA levels, such as hypertension, chronic kidney disease, and cardiovascular disease, Dr. Dalbeth said.
Audience member Daniel H. Solomon, MD, of Brigham and Women’s Hospital, Boston, said after the presentation that it is possible that age might not be independent of sUA level because it’s unknown when patients first had hyperuricemia, and so it could just serve as a marker of the duration of the effect of hyperuricemia. “You showed us that the longer you wait for people who have higher [sUA] levels, the more likely you are to observe gout. So it’s probably some mixture of duration [of hyperuricemia] and age,” he said.
Dr. Dalbeth agreed, saying that it could also help to explain why the incidence of gout is lower at younger ages in women but then subsequently becomes higher.
The Health Research Council of New Zealand supported the research. Dr. Dalbeth reported receiving consulting fees, grants, or speaking fees from Takeda, Horizon, Menarini, AstraZeneca, Ardea Biosciences, Pfizer, and Cymabay, but none are related to this study. Two other authors also had several financial disclosures, but none of the others did.
SAN DIEGO – The incidence of gout is strongly linked to patients’ concentration of serum uric acid over time, but even so, less than half of patients with levels of 10 mg/dL or above develop the condition by 15 years, according to the largest individual person-level analysis to examine the relationship.
The incidence of gout rose from about 1% after 15 years in patients with a serum uric acid (sUA) level of less than 6 mg/dL to almost 49% in those with 10 mg/dL or higher in the study, which implies “a long period of hyperuricemia preceding the onset of clinical gout” and also “supports a role for additional factors in the pathogenesis of gout,” Nicola Dalbeth, MD, said in her presentation of the results at the annual meeting of the American College of Rheumatology.
Dr. Dalbeth and her associates found four studies in a search of PubMed and the Database of Genotype and Phenotype from Jan. 1, 1980, to June 11, 2016, that met the inclusion criteria of containing publicly available participant level data, recorded incident gout (via classification criteria, doctor’s diagnosis, or self report of disease), and had a minimum of 3 years of follow-up. The four studies were the Atherosclerosis Risk in Communities study, the Coronary Artery Risk Development in Young Adults study, the original cohort of the Framingham Heart Study, and the offspring cohort of the Framingham Heart Study, comprising 18,889 individuals who were gout free at the beginning of follow-up, which lasted a mean of 11.2 years.
In all studies combined, the incidence of gout at an sUA level of less than 6 mg/dL steadily increased from 0.21% at 3 years of follow-up to 1.12% at 15 years. In contrast, sUA at 10 mg/dL or higher led to gout in 10.00% at 3 years and in 48.57% at 15 years.
The same general pattern held for the incidence of gout in both men and women, although men had a higher incidence across nearly all sUA concentration ranges.
Female sex provided a 30% reduced risk of gout, and European ethnicity nearly halved the risk for gout, compared with non-Europeans, The risk for gout rose across decades of age, starting at 40-49 years, and also increased significantly for each 1-mg/dL interval of sUA starting at 6 mg/dL.
The study’s conclusions are limited by the use of variable definitions of gout and how it was ascertained. In addition, the study did not analyze other endpoints that are associated with hyperuricemia and may be relevant to discuss in counseling people with elevated sUA levels, such as hypertension, chronic kidney disease, and cardiovascular disease, Dr. Dalbeth said.
Audience member Daniel H. Solomon, MD, of Brigham and Women’s Hospital, Boston, said after the presentation that it is possible that age might not be independent of sUA level because it’s unknown when patients first had hyperuricemia, and so it could just serve as a marker of the duration of the effect of hyperuricemia. “You showed us that the longer you wait for people who have higher [sUA] levels, the more likely you are to observe gout. So it’s probably some mixture of duration [of hyperuricemia] and age,” he said.
Dr. Dalbeth agreed, saying that it could also help to explain why the incidence of gout is lower at younger ages in women but then subsequently becomes higher.
The Health Research Council of New Zealand supported the research. Dr. Dalbeth reported receiving consulting fees, grants, or speaking fees from Takeda, Horizon, Menarini, AstraZeneca, Ardea Biosciences, Pfizer, and Cymabay, but none are related to this study. Two other authors also had several financial disclosures, but none of the others did.
SAN DIEGO – The incidence of gout is strongly linked to patients’ concentration of serum uric acid over time, but even so, less than half of patients with levels of 10 mg/dL or above develop the condition by 15 years, according to the largest individual person-level analysis to examine the relationship.
The incidence of gout rose from about 1% after 15 years in patients with a serum uric acid (sUA) level of less than 6 mg/dL to almost 49% in those with 10 mg/dL or higher in the study, which implies “a long period of hyperuricemia preceding the onset of clinical gout” and also “supports a role for additional factors in the pathogenesis of gout,” Nicola Dalbeth, MD, said in her presentation of the results at the annual meeting of the American College of Rheumatology.
Dr. Dalbeth and her associates found four studies in a search of PubMed and the Database of Genotype and Phenotype from Jan. 1, 1980, to June 11, 2016, that met the inclusion criteria of containing publicly available participant level data, recorded incident gout (via classification criteria, doctor’s diagnosis, or self report of disease), and had a minimum of 3 years of follow-up. The four studies were the Atherosclerosis Risk in Communities study, the Coronary Artery Risk Development in Young Adults study, the original cohort of the Framingham Heart Study, and the offspring cohort of the Framingham Heart Study, comprising 18,889 individuals who were gout free at the beginning of follow-up, which lasted a mean of 11.2 years.
In all studies combined, the incidence of gout at an sUA level of less than 6 mg/dL steadily increased from 0.21% at 3 years of follow-up to 1.12% at 15 years. In contrast, sUA at 10 mg/dL or higher led to gout in 10.00% at 3 years and in 48.57% at 15 years.
The same general pattern held for the incidence of gout in both men and women, although men had a higher incidence across nearly all sUA concentration ranges.
Female sex provided a 30% reduced risk of gout, and European ethnicity nearly halved the risk for gout, compared with non-Europeans, The risk for gout rose across decades of age, starting at 40-49 years, and also increased significantly for each 1-mg/dL interval of sUA starting at 6 mg/dL.
The study’s conclusions are limited by the use of variable definitions of gout and how it was ascertained. In addition, the study did not analyze other endpoints that are associated with hyperuricemia and may be relevant to discuss in counseling people with elevated sUA levels, such as hypertension, chronic kidney disease, and cardiovascular disease, Dr. Dalbeth said.
Audience member Daniel H. Solomon, MD, of Brigham and Women’s Hospital, Boston, said after the presentation that it is possible that age might not be independent of sUA level because it’s unknown when patients first had hyperuricemia, and so it could just serve as a marker of the duration of the effect of hyperuricemia. “You showed us that the longer you wait for people who have higher [sUA] levels, the more likely you are to observe gout. So it’s probably some mixture of duration [of hyperuricemia] and age,” he said.
Dr. Dalbeth agreed, saying that it could also help to explain why the incidence of gout is lower at younger ages in women but then subsequently becomes higher.
The Health Research Council of New Zealand supported the research. Dr. Dalbeth reported receiving consulting fees, grants, or speaking fees from Takeda, Horizon, Menarini, AstraZeneca, Ardea Biosciences, Pfizer, and Cymabay, but none are related to this study. Two other authors also had several financial disclosures, but none of the others did.
AT ACR 2017
Key clinical point:
Major finding: The incidence of gout rose to about 1% after 15 years in patients with a serum uric acid (sUA) level of less than 6 mg/dL to almost 49% in those with 10 mg/dL or higher.
Data source: An analysis of 18,889 participants in four longitudinal observational cohort studies for whom baseline serum uric acid levels were available.
Disclosures: The Health Research Council of New Zealand supported the research. Dr. Dalbeth reported receiving consulting fees, grants, or speaking fees from Takeda, Horizon, Menarini, AstraZeneca, Ardea Biosciences, Pfizer, and Cymabay, but none are related to this study. Two other authors also had several financial disclosures, but none of the others did.
Legislative landscape affecting rheumatology has potential wins but many challenges
SAN DIEGO – , but ongoing efforts to advocate for the specialty and patients are showing signs of paying off in some areas, Angus Worthing, MD, said at the annual meeting of the American College of Rheumatology.
Dr. Worthing, who is chair of the ACR’s Government Affairs Committee and a practicing rheumatologist in the Washington area, encouraged rheumatologists to become involved in advocacy efforts and asked members of the audience at the meeting to visit the ACR’s advocacy website to learn how to help.
The ACR supports a group of bills that have been introduced in either the House or Senate that should have an effect on alleviating the projected shortage of rheumatologists across the United States through 2030. These bills will help, although much of the effort to address the shortage and maldistribution of rheumatologists across the United States will “probably be solved at the local level. It’s not going to be a federal solution. It will be relationships and treatment programs between primary care and rheumatology care that are very local,” Dr. Worthing said.
The Conrad State 30 and Physician Access Reauthorization Act (H.R. 2141, S. 898) aims to streamline visas for foreign physicians to practice in underserved areas.
The Resident Physician Shortage Reduction Act of 2017 (H.R. 2267) would increase for the first time since 1997 the number of graduate medical education residency slots in the United States.
The Ensuring Children’s Access to Specialty Care Act of 2017 (S. 989) allows pediatric subspecialists, including pediatric rheumatologists, to get access to the National Health Service Corps loan repayment program when they work in underserved areas.
More recently, in spring 2017 the American Medical Association played a big role in getting the Trump administration to reverse its stance on not allowing premium processing of H1-B visas for professionals such as physicians. If this had gone into effect, all the rheumatology fellows in training who were going to be practicing – some in underserved areas – might have been forced to return to their home country because of a lack of time to get their H1-B visa processed before finishing their fellowship, Dr. Worthing said.
Affordable Care Act (ACA)
- Provide sufficient, affordable, continuous coverage that encourages access to high-quality care for all.
- Prohibit exclusions based on preexisting conditions.
- Allow children to remain on parent’s insurance until age 26 years.
- Remove excessive administrative burdens that take focus away from patient care.
- Cap annual out-of-pocket costs and ban lifetime limits.
- Have affordable premiums, deductibles, and cost sharing.
- Continue the 10 essential health benefits that are required for ACA marketplace plans.
Alliance for Transparent & Affordable Prescriptions (ATAP)
The ACR convened this alliance along with the Coalition of State Rheumatology Organizations, the Global Healthy Living Foundation, the Association of Women in Rheumatology, the Rheumatology Nurses Society, and others to try to bring transparency to how pharmacy benefit managers (PBMs) operate in getting certain drugs on the formularies of payers. The ATAP recently had some success in making lawmakers aware of the PBM’s role in influencing drug prices via rebates to drug manufacturers. At a Congressional hearing in Oct. 2017, after many visits from rheumatologists and members of ATAP, the members of the Senate Committee on Health, Education, Labor, and Pensions “held the feet of these PBMs to the fire a little bit asking them about these rebates,” Dr. Worthing said, where at one point committee chair Sen. Lamar Alexander (R-Tenn.) asked, “ ‘Do we really need these rebates?’ ”
National Institutes of Health budget
After the National Institutes of Health received a $2 billion increase in funding for fiscal year 2017, the Trump administration proposed last summer to cut the NIH budget by 22%. Since then, however, bills to increase the NIH budget by $1.1 billion from the House and by $2 billion from the Senate have made their way through committees. But a budget must be passed by Congress and then signed by the president to make a potential budget increase a reality. Otherwise, a continuing resolution would leave the current level of funding in place through fiscal year 2018, Dr. Worthing noted.
Patients’ Access to Treatments Act of 2017 (H.R. 2999)
This bill has been raised for a fourth time after not making it past committees in previous Congresses, but the prospects for it passing appear somewhat better this time around, Dr. Worthing said. It would prevent insurance companies from putting drugs in specialty tiers that require patients to pay increasingly higher rates of coinsurance for the drugs on different tiers.
“It has been gathering momentum. We hope to get it across the finish line. And if we don’t get this across, then we’ll join with the coalition that rheumatology has formed around this issue of access to specialty treatments some other way, because this is a burning issue for us and our patients,” he said.
Medicare Access to Rehabilitation Services Act of 2017 (H.R. 807 and S. 253)
This bill would repeal the annual cap that was placed on rehabilitation services for patients covered by Medicare in 1997. The bill has bipartisan, majority support and has been gaining momentum for the past 4 years, Dr. Worthing said. It was advanced from both Senate and House committees in Oct. 2017.
SAN DIEGO – , but ongoing efforts to advocate for the specialty and patients are showing signs of paying off in some areas, Angus Worthing, MD, said at the annual meeting of the American College of Rheumatology.
Dr. Worthing, who is chair of the ACR’s Government Affairs Committee and a practicing rheumatologist in the Washington area, encouraged rheumatologists to become involved in advocacy efforts and asked members of the audience at the meeting to visit the ACR’s advocacy website to learn how to help.
The ACR supports a group of bills that have been introduced in either the House or Senate that should have an effect on alleviating the projected shortage of rheumatologists across the United States through 2030. These bills will help, although much of the effort to address the shortage and maldistribution of rheumatologists across the United States will “probably be solved at the local level. It’s not going to be a federal solution. It will be relationships and treatment programs between primary care and rheumatology care that are very local,” Dr. Worthing said.
The Conrad State 30 and Physician Access Reauthorization Act (H.R. 2141, S. 898) aims to streamline visas for foreign physicians to practice in underserved areas.
The Resident Physician Shortage Reduction Act of 2017 (H.R. 2267) would increase for the first time since 1997 the number of graduate medical education residency slots in the United States.
The Ensuring Children’s Access to Specialty Care Act of 2017 (S. 989) allows pediatric subspecialists, including pediatric rheumatologists, to get access to the National Health Service Corps loan repayment program when they work in underserved areas.
More recently, in spring 2017 the American Medical Association played a big role in getting the Trump administration to reverse its stance on not allowing premium processing of H1-B visas for professionals such as physicians. If this had gone into effect, all the rheumatology fellows in training who were going to be practicing – some in underserved areas – might have been forced to return to their home country because of a lack of time to get their H1-B visa processed before finishing their fellowship, Dr. Worthing said.
Affordable Care Act (ACA)
- Provide sufficient, affordable, continuous coverage that encourages access to high-quality care for all.
- Prohibit exclusions based on preexisting conditions.
- Allow children to remain on parent’s insurance until age 26 years.
- Remove excessive administrative burdens that take focus away from patient care.
- Cap annual out-of-pocket costs and ban lifetime limits.
- Have affordable premiums, deductibles, and cost sharing.
- Continue the 10 essential health benefits that are required for ACA marketplace plans.
Alliance for Transparent & Affordable Prescriptions (ATAP)
The ACR convened this alliance along with the Coalition of State Rheumatology Organizations, the Global Healthy Living Foundation, the Association of Women in Rheumatology, the Rheumatology Nurses Society, and others to try to bring transparency to how pharmacy benefit managers (PBMs) operate in getting certain drugs on the formularies of payers. The ATAP recently had some success in making lawmakers aware of the PBM’s role in influencing drug prices via rebates to drug manufacturers. At a Congressional hearing in Oct. 2017, after many visits from rheumatologists and members of ATAP, the members of the Senate Committee on Health, Education, Labor, and Pensions “held the feet of these PBMs to the fire a little bit asking them about these rebates,” Dr. Worthing said, where at one point committee chair Sen. Lamar Alexander (R-Tenn.) asked, “ ‘Do we really need these rebates?’ ”
National Institutes of Health budget
After the National Institutes of Health received a $2 billion increase in funding for fiscal year 2017, the Trump administration proposed last summer to cut the NIH budget by 22%. Since then, however, bills to increase the NIH budget by $1.1 billion from the House and by $2 billion from the Senate have made their way through committees. But a budget must be passed by Congress and then signed by the president to make a potential budget increase a reality. Otherwise, a continuing resolution would leave the current level of funding in place through fiscal year 2018, Dr. Worthing noted.
Patients’ Access to Treatments Act of 2017 (H.R. 2999)
This bill has been raised for a fourth time after not making it past committees in previous Congresses, but the prospects for it passing appear somewhat better this time around, Dr. Worthing said. It would prevent insurance companies from putting drugs in specialty tiers that require patients to pay increasingly higher rates of coinsurance for the drugs on different tiers.
“It has been gathering momentum. We hope to get it across the finish line. And if we don’t get this across, then we’ll join with the coalition that rheumatology has formed around this issue of access to specialty treatments some other way, because this is a burning issue for us and our patients,” he said.
Medicare Access to Rehabilitation Services Act of 2017 (H.R. 807 and S. 253)
This bill would repeal the annual cap that was placed on rehabilitation services for patients covered by Medicare in 1997. The bill has bipartisan, majority support and has been gaining momentum for the past 4 years, Dr. Worthing said. It was advanced from both Senate and House committees in Oct. 2017.
SAN DIEGO – , but ongoing efforts to advocate for the specialty and patients are showing signs of paying off in some areas, Angus Worthing, MD, said at the annual meeting of the American College of Rheumatology.
Dr. Worthing, who is chair of the ACR’s Government Affairs Committee and a practicing rheumatologist in the Washington area, encouraged rheumatologists to become involved in advocacy efforts and asked members of the audience at the meeting to visit the ACR’s advocacy website to learn how to help.
The ACR supports a group of bills that have been introduced in either the House or Senate that should have an effect on alleviating the projected shortage of rheumatologists across the United States through 2030. These bills will help, although much of the effort to address the shortage and maldistribution of rheumatologists across the United States will “probably be solved at the local level. It’s not going to be a federal solution. It will be relationships and treatment programs between primary care and rheumatology care that are very local,” Dr. Worthing said.
The Conrad State 30 and Physician Access Reauthorization Act (H.R. 2141, S. 898) aims to streamline visas for foreign physicians to practice in underserved areas.
The Resident Physician Shortage Reduction Act of 2017 (H.R. 2267) would increase for the first time since 1997 the number of graduate medical education residency slots in the United States.
The Ensuring Children’s Access to Specialty Care Act of 2017 (S. 989) allows pediatric subspecialists, including pediatric rheumatologists, to get access to the National Health Service Corps loan repayment program when they work in underserved areas.
More recently, in spring 2017 the American Medical Association played a big role in getting the Trump administration to reverse its stance on not allowing premium processing of H1-B visas for professionals such as physicians. If this had gone into effect, all the rheumatology fellows in training who were going to be practicing – some in underserved areas – might have been forced to return to their home country because of a lack of time to get their H1-B visa processed before finishing their fellowship, Dr. Worthing said.
Affordable Care Act (ACA)
- Provide sufficient, affordable, continuous coverage that encourages access to high-quality care for all.
- Prohibit exclusions based on preexisting conditions.
- Allow children to remain on parent’s insurance until age 26 years.
- Remove excessive administrative burdens that take focus away from patient care.
- Cap annual out-of-pocket costs and ban lifetime limits.
- Have affordable premiums, deductibles, and cost sharing.
- Continue the 10 essential health benefits that are required for ACA marketplace plans.
Alliance for Transparent & Affordable Prescriptions (ATAP)
The ACR convened this alliance along with the Coalition of State Rheumatology Organizations, the Global Healthy Living Foundation, the Association of Women in Rheumatology, the Rheumatology Nurses Society, and others to try to bring transparency to how pharmacy benefit managers (PBMs) operate in getting certain drugs on the formularies of payers. The ATAP recently had some success in making lawmakers aware of the PBM’s role in influencing drug prices via rebates to drug manufacturers. At a Congressional hearing in Oct. 2017, after many visits from rheumatologists and members of ATAP, the members of the Senate Committee on Health, Education, Labor, and Pensions “held the feet of these PBMs to the fire a little bit asking them about these rebates,” Dr. Worthing said, where at one point committee chair Sen. Lamar Alexander (R-Tenn.) asked, “ ‘Do we really need these rebates?’ ”
National Institutes of Health budget
After the National Institutes of Health received a $2 billion increase in funding for fiscal year 2017, the Trump administration proposed last summer to cut the NIH budget by 22%. Since then, however, bills to increase the NIH budget by $1.1 billion from the House and by $2 billion from the Senate have made their way through committees. But a budget must be passed by Congress and then signed by the president to make a potential budget increase a reality. Otherwise, a continuing resolution would leave the current level of funding in place through fiscal year 2018, Dr. Worthing noted.
Patients’ Access to Treatments Act of 2017 (H.R. 2999)
This bill has been raised for a fourth time after not making it past committees in previous Congresses, but the prospects for it passing appear somewhat better this time around, Dr. Worthing said. It would prevent insurance companies from putting drugs in specialty tiers that require patients to pay increasingly higher rates of coinsurance for the drugs on different tiers.
“It has been gathering momentum. We hope to get it across the finish line. And if we don’t get this across, then we’ll join with the coalition that rheumatology has formed around this issue of access to specialty treatments some other way, because this is a burning issue for us and our patients,” he said.
Medicare Access to Rehabilitation Services Act of 2017 (H.R. 807 and S. 253)
This bill would repeal the annual cap that was placed on rehabilitation services for patients covered by Medicare in 1997. The bill has bipartisan, majority support and has been gaining momentum for the past 4 years, Dr. Worthing said. It was advanced from both Senate and House committees in Oct. 2017.
AT ACR 2017
New RA JAK inhibitor, monoclonal antibody trial results scheduled for ACR 2017
New results from several investigational oral Janus kinase inhibitor trials and an antifractalkine monoclonal antibody trial for patients with rheumatoid arthritis will be made available for the first time to attendees of the annual meeting of the American College of Rheumatology on Nov. 6 and 7 in San Diego.
Selective JAK-1 inhibitor upadacitinib
Two double-blind, randomized, controlled phase 3 studies of the oral, selective JAK-1 inhibitor upadacitinib (ABT-494) will be presented at the meeting, both involving once-daily extended-release formulations of the drug at 15 mg or 30 mg. The first trial, to be presented during an ACR abstract session on Monday, Nov. 6, showed that the drug met ACR 20 response criteria at significantly higher rates than did placebo at week 12 (63.8% for 15 mg, 66.2% for 30 mg, and 35.7% for placebo) in 661 patients with active RA and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Patients on the study drug also achieved low disease activity (28-joint Disease Activity Score using C-reactive protein [DAS28-CRP] of 3.2 or less) in higher proportions than did those who received placebo (48.4% for 15 mg, 47.9% for 30 mg, and 17.2% for placebo). More infections occurred in patients on 15 mg and 30 mg upadacitinib (29.0% and 31.5%, respectively), compared with placebo (21.3%), but there were no differences in serious infections. Three of the total four cases of herpes zoster infection were in patients taking upadacitinib.
A second upadacitinib trial, which involved patients on stable csDMARD therapy who could not tolerate or had disease refractory to a biologic DMARD, will be presented during a late-breaking poster session on Tuesday, Nov. 7. The study randomized 499 patients who had severe, refractory disease for a mean duration of 13 years. At 12 weeks, treatment with upadacitinib resulted in ACR 20 responses in 64.6% at 15 mg and 56.4% at 30 mg, compared with 28.4% for placebo. Responses at 12 weeks of 3.2 or less for DAS28-CRP also occurred at significantly higher rates of 43.3% for 15 mg and 42.4% for 30 mg, compared with 14.2% for placebo. Patients who were switched from placebo to active treatment at week 12 also achieved these responses at week 24, and the people who stayed on treatment with upadacitinib maintained or improved their response at week 24. More adverse events and infections tended to occur with upadacitinib at 30 mg than with 15 mg, and there were more herpes zoster infections with 30 mg (n = 4) vs. 15 mg (n = 1) and placebo (n = 1).
Antifractalkine monoclonal antibody
The Monday afternoon RA therapy abstract session will also feature the first-in-patient results at 52 weeks for the antifractalkine monoclonal antibody E6011 in an open-label phase 1/2 study of Japanese RA patients with active disease who had an inadequate response or intolerance to methotrexate or a TNF inhibitor. The results from the small trial of the biologic, which targets the chemokine that regulates chemotaxis and the adhesion of inflammatory cells that express CX3C chemokine receptor 1 (CX3CR1), indicate that the treatment has durable efficacy and is safe and well tolerated. Adverse events (AEs) developed in 84% of 28 patients who participated in the 52-week extension study, including a rate of 48% for treatment-emergent adverse events (TEAEs) and 14% for serious AEs. ACR 20 rates at week 52 ranged from 58% for 100 mg of E6011 to 73% for 200 mg and 60% for 400 mg.
Filgotinib safety in an extension trial
The long-term, open-label results from two phase 2b studies of the JAK-1 inhibitor filgotinib that’s in development for RA also will be presented during the same Monday abstract session. These safety data out to 84 weeks from the long-term extension study of the DARWIN 1 and 2 studies, called DARWIN 3, show that, among patients who received at least one dose of filgotinib 100 mg twice daily or 200 mg once daily in addition to methotrexate, the rate of TEAEs ranged from about 146 to 153 per 100 patient-years of exposure (PYE), including about 41-45 infections per 100 PYE. For filgotinib monotherapy, the rate of TEAEs was 150 per 100 PYE for 200 mg once daily, including 38 infections per 100 PYE.
Total cholesterol of 200-239 mg/dL occurred at a rate of about 79 per 100 PYE and a level of 240 mg/dL or greater was seen in 61-64 per 100 PYE for patients who took filgotinib plus methotrexate. Filgotinib monotherapy at 200 mg once daily gave rates of about 94 and 71 per 100 PYE for those respective total cholesterol levels.
New results from several investigational oral Janus kinase inhibitor trials and an antifractalkine monoclonal antibody trial for patients with rheumatoid arthritis will be made available for the first time to attendees of the annual meeting of the American College of Rheumatology on Nov. 6 and 7 in San Diego.
Selective JAK-1 inhibitor upadacitinib
Two double-blind, randomized, controlled phase 3 studies of the oral, selective JAK-1 inhibitor upadacitinib (ABT-494) will be presented at the meeting, both involving once-daily extended-release formulations of the drug at 15 mg or 30 mg. The first trial, to be presented during an ACR abstract session on Monday, Nov. 6, showed that the drug met ACR 20 response criteria at significantly higher rates than did placebo at week 12 (63.8% for 15 mg, 66.2% for 30 mg, and 35.7% for placebo) in 661 patients with active RA and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Patients on the study drug also achieved low disease activity (28-joint Disease Activity Score using C-reactive protein [DAS28-CRP] of 3.2 or less) in higher proportions than did those who received placebo (48.4% for 15 mg, 47.9% for 30 mg, and 17.2% for placebo). More infections occurred in patients on 15 mg and 30 mg upadacitinib (29.0% and 31.5%, respectively), compared with placebo (21.3%), but there were no differences in serious infections. Three of the total four cases of herpes zoster infection were in patients taking upadacitinib.
A second upadacitinib trial, which involved patients on stable csDMARD therapy who could not tolerate or had disease refractory to a biologic DMARD, will be presented during a late-breaking poster session on Tuesday, Nov. 7. The study randomized 499 patients who had severe, refractory disease for a mean duration of 13 years. At 12 weeks, treatment with upadacitinib resulted in ACR 20 responses in 64.6% at 15 mg and 56.4% at 30 mg, compared with 28.4% for placebo. Responses at 12 weeks of 3.2 or less for DAS28-CRP also occurred at significantly higher rates of 43.3% for 15 mg and 42.4% for 30 mg, compared with 14.2% for placebo. Patients who were switched from placebo to active treatment at week 12 also achieved these responses at week 24, and the people who stayed on treatment with upadacitinib maintained or improved their response at week 24. More adverse events and infections tended to occur with upadacitinib at 30 mg than with 15 mg, and there were more herpes zoster infections with 30 mg (n = 4) vs. 15 mg (n = 1) and placebo (n = 1).
Antifractalkine monoclonal antibody
The Monday afternoon RA therapy abstract session will also feature the first-in-patient results at 52 weeks for the antifractalkine monoclonal antibody E6011 in an open-label phase 1/2 study of Japanese RA patients with active disease who had an inadequate response or intolerance to methotrexate or a TNF inhibitor. The results from the small trial of the biologic, which targets the chemokine that regulates chemotaxis and the adhesion of inflammatory cells that express CX3C chemokine receptor 1 (CX3CR1), indicate that the treatment has durable efficacy and is safe and well tolerated. Adverse events (AEs) developed in 84% of 28 patients who participated in the 52-week extension study, including a rate of 48% for treatment-emergent adverse events (TEAEs) and 14% for serious AEs. ACR 20 rates at week 52 ranged from 58% for 100 mg of E6011 to 73% for 200 mg and 60% for 400 mg.
Filgotinib safety in an extension trial
The long-term, open-label results from two phase 2b studies of the JAK-1 inhibitor filgotinib that’s in development for RA also will be presented during the same Monday abstract session. These safety data out to 84 weeks from the long-term extension study of the DARWIN 1 and 2 studies, called DARWIN 3, show that, among patients who received at least one dose of filgotinib 100 mg twice daily or 200 mg once daily in addition to methotrexate, the rate of TEAEs ranged from about 146 to 153 per 100 patient-years of exposure (PYE), including about 41-45 infections per 100 PYE. For filgotinib monotherapy, the rate of TEAEs was 150 per 100 PYE for 200 mg once daily, including 38 infections per 100 PYE.
Total cholesterol of 200-239 mg/dL occurred at a rate of about 79 per 100 PYE and a level of 240 mg/dL or greater was seen in 61-64 per 100 PYE for patients who took filgotinib plus methotrexate. Filgotinib monotherapy at 200 mg once daily gave rates of about 94 and 71 per 100 PYE for those respective total cholesterol levels.
New results from several investigational oral Janus kinase inhibitor trials and an antifractalkine monoclonal antibody trial for patients with rheumatoid arthritis will be made available for the first time to attendees of the annual meeting of the American College of Rheumatology on Nov. 6 and 7 in San Diego.
Selective JAK-1 inhibitor upadacitinib
Two double-blind, randomized, controlled phase 3 studies of the oral, selective JAK-1 inhibitor upadacitinib (ABT-494) will be presented at the meeting, both involving once-daily extended-release formulations of the drug at 15 mg or 30 mg. The first trial, to be presented during an ACR abstract session on Monday, Nov. 6, showed that the drug met ACR 20 response criteria at significantly higher rates than did placebo at week 12 (63.8% for 15 mg, 66.2% for 30 mg, and 35.7% for placebo) in 661 patients with active RA and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Patients on the study drug also achieved low disease activity (28-joint Disease Activity Score using C-reactive protein [DAS28-CRP] of 3.2 or less) in higher proportions than did those who received placebo (48.4% for 15 mg, 47.9% for 30 mg, and 17.2% for placebo). More infections occurred in patients on 15 mg and 30 mg upadacitinib (29.0% and 31.5%, respectively), compared with placebo (21.3%), but there were no differences in serious infections. Three of the total four cases of herpes zoster infection were in patients taking upadacitinib.
A second upadacitinib trial, which involved patients on stable csDMARD therapy who could not tolerate or had disease refractory to a biologic DMARD, will be presented during a late-breaking poster session on Tuesday, Nov. 7. The study randomized 499 patients who had severe, refractory disease for a mean duration of 13 years. At 12 weeks, treatment with upadacitinib resulted in ACR 20 responses in 64.6% at 15 mg and 56.4% at 30 mg, compared with 28.4% for placebo. Responses at 12 weeks of 3.2 or less for DAS28-CRP also occurred at significantly higher rates of 43.3% for 15 mg and 42.4% for 30 mg, compared with 14.2% for placebo. Patients who were switched from placebo to active treatment at week 12 also achieved these responses at week 24, and the people who stayed on treatment with upadacitinib maintained or improved their response at week 24. More adverse events and infections tended to occur with upadacitinib at 30 mg than with 15 mg, and there were more herpes zoster infections with 30 mg (n = 4) vs. 15 mg (n = 1) and placebo (n = 1).
Antifractalkine monoclonal antibody
The Monday afternoon RA therapy abstract session will also feature the first-in-patient results at 52 weeks for the antifractalkine monoclonal antibody E6011 in an open-label phase 1/2 study of Japanese RA patients with active disease who had an inadequate response or intolerance to methotrexate or a TNF inhibitor. The results from the small trial of the biologic, which targets the chemokine that regulates chemotaxis and the adhesion of inflammatory cells that express CX3C chemokine receptor 1 (CX3CR1), indicate that the treatment has durable efficacy and is safe and well tolerated. Adverse events (AEs) developed in 84% of 28 patients who participated in the 52-week extension study, including a rate of 48% for treatment-emergent adverse events (TEAEs) and 14% for serious AEs. ACR 20 rates at week 52 ranged from 58% for 100 mg of E6011 to 73% for 200 mg and 60% for 400 mg.
Filgotinib safety in an extension trial
The long-term, open-label results from two phase 2b studies of the JAK-1 inhibitor filgotinib that’s in development for RA also will be presented during the same Monday abstract session. These safety data out to 84 weeks from the long-term extension study of the DARWIN 1 and 2 studies, called DARWIN 3, show that, among patients who received at least one dose of filgotinib 100 mg twice daily or 200 mg once daily in addition to methotrexate, the rate of TEAEs ranged from about 146 to 153 per 100 patient-years of exposure (PYE), including about 41-45 infections per 100 PYE. For filgotinib monotherapy, the rate of TEAEs was 150 per 100 PYE for 200 mg once daily, including 38 infections per 100 PYE.
Total cholesterol of 200-239 mg/dL occurred at a rate of about 79 per 100 PYE and a level of 240 mg/dL or greater was seen in 61-64 per 100 PYE for patients who took filgotinib plus methotrexate. Filgotinib monotherapy at 200 mg once daily gave rates of about 94 and 71 per 100 PYE for those respective total cholesterol levels.
FROM ACR 2017
Precision medicine’s future in rheumatic diseases outlined at ACR 2017
The treatment and prevention of rheumatic diseases through a precision medicine approach that takes into account individual variability in genes, environment, and lifestyle has not yet become a reality in clinical practice, but researchers in the field hope to demonstrate its potential at a course before and a session during the annual meeting of the American College of Rheumatology in San Diego.
In a 2-day premeeting course that begins on Friday, Nov. 3, a multidisciplinary faculty will discuss the technologies involved in precision medicine research; the complexities and challenges of identifying optimal drug treatments for rheumatic diseases; past, ongoing, and future research initiatives in precision medicine affecting rheumatic diseases; and how large data-set analysis and collaborative networks of researchers can shape its future.
Later, during the meeting on the afternoon of Monday, Nov. 6, an ACR session will look at how precision medicine research in patients with systemic lupus erythematosus (SLE) has laid groundwork to improve clinical trial design and the implementation of more tailored treatment for SLE and other complex autoimmune diseases.
The first day of the 2-day premeeting course will cover current approaches to studying familial and pediatric rheumatic diseases as well as an outline of how precision medicine could affect treatment approaches to SLE. Later in the day, presentations will focus on examples of personalized medicine approaches that have been derived from studies of cancer genomics and familial syndromes and the genetic underpinning of different responses to medications. The impact of direct-to-consumer genetic testing will also be discussed. Abstract presentations at the end of the day will focus on new genetic biomarkers that differentiate active disease from remission in granulomatosis with polyangiitis and mutations related to cancer-associated myositis.
The second day of the course on Saturday, Nov. 4, will focus on the technology behind precision medicine, followed by data analysis and integration into clinical practice. Technology presentations aim to demonstrate how transcriptional analysis of single immune cells and epigenetics in small numbers of cells can provide information about disease activity and prognosis. Examples of how multiple types of data can be integrated to form a picture of the pathogenesis of diseases such as rheumatoid arthritis will be discussed. Two abstract presentations will serve to show how analysis of tissue-specific serum biomarkers can identify rheumatoid arthritis patients with structural progression and how the presence of a specific antibody can predict better response to anti–tumor necrosis factor treatment and better disease control over time. In the afternoon, sessions will focus on analyzing single-cell data in key cell subpopulations in rheumatic disease and specifically address immune cell interactions across systems in SLE.
On Monday at 1:00 p.m., Maria Virginia Pascual, PhD, director of the Drukier Institute for Children’s Health and the Ronay A. Menschel Professor of Pediatrics at Cornell University in New York will speak in the ACR session, “Precision Medicine for Rheumatic Disease: Closer Than You Think?” Dr. Pascual will provide an overview of her lab’s recent work in transcriptional profiling of pediatric SLE patients, which demonstrates the potential value of immunomonitoring in order to stratify patients into discrete molecular groups to make clinical trial design better and offer more targeted therapies.
The treatment and prevention of rheumatic diseases through a precision medicine approach that takes into account individual variability in genes, environment, and lifestyle has not yet become a reality in clinical practice, but researchers in the field hope to demonstrate its potential at a course before and a session during the annual meeting of the American College of Rheumatology in San Diego.
In a 2-day premeeting course that begins on Friday, Nov. 3, a multidisciplinary faculty will discuss the technologies involved in precision medicine research; the complexities and challenges of identifying optimal drug treatments for rheumatic diseases; past, ongoing, and future research initiatives in precision medicine affecting rheumatic diseases; and how large data-set analysis and collaborative networks of researchers can shape its future.
Later, during the meeting on the afternoon of Monday, Nov. 6, an ACR session will look at how precision medicine research in patients with systemic lupus erythematosus (SLE) has laid groundwork to improve clinical trial design and the implementation of more tailored treatment for SLE and other complex autoimmune diseases.
The first day of the 2-day premeeting course will cover current approaches to studying familial and pediatric rheumatic diseases as well as an outline of how precision medicine could affect treatment approaches to SLE. Later in the day, presentations will focus on examples of personalized medicine approaches that have been derived from studies of cancer genomics and familial syndromes and the genetic underpinning of different responses to medications. The impact of direct-to-consumer genetic testing will also be discussed. Abstract presentations at the end of the day will focus on new genetic biomarkers that differentiate active disease from remission in granulomatosis with polyangiitis and mutations related to cancer-associated myositis.
The second day of the course on Saturday, Nov. 4, will focus on the technology behind precision medicine, followed by data analysis and integration into clinical practice. Technology presentations aim to demonstrate how transcriptional analysis of single immune cells and epigenetics in small numbers of cells can provide information about disease activity and prognosis. Examples of how multiple types of data can be integrated to form a picture of the pathogenesis of diseases such as rheumatoid arthritis will be discussed. Two abstract presentations will serve to show how analysis of tissue-specific serum biomarkers can identify rheumatoid arthritis patients with structural progression and how the presence of a specific antibody can predict better response to anti–tumor necrosis factor treatment and better disease control over time. In the afternoon, sessions will focus on analyzing single-cell data in key cell subpopulations in rheumatic disease and specifically address immune cell interactions across systems in SLE.
On Monday at 1:00 p.m., Maria Virginia Pascual, PhD, director of the Drukier Institute for Children’s Health and the Ronay A. Menschel Professor of Pediatrics at Cornell University in New York will speak in the ACR session, “Precision Medicine for Rheumatic Disease: Closer Than You Think?” Dr. Pascual will provide an overview of her lab’s recent work in transcriptional profiling of pediatric SLE patients, which demonstrates the potential value of immunomonitoring in order to stratify patients into discrete molecular groups to make clinical trial design better and offer more targeted therapies.
The treatment and prevention of rheumatic diseases through a precision medicine approach that takes into account individual variability in genes, environment, and lifestyle has not yet become a reality in clinical practice, but researchers in the field hope to demonstrate its potential at a course before and a session during the annual meeting of the American College of Rheumatology in San Diego.
In a 2-day premeeting course that begins on Friday, Nov. 3, a multidisciplinary faculty will discuss the technologies involved in precision medicine research; the complexities and challenges of identifying optimal drug treatments for rheumatic diseases; past, ongoing, and future research initiatives in precision medicine affecting rheumatic diseases; and how large data-set analysis and collaborative networks of researchers can shape its future.
Later, during the meeting on the afternoon of Monday, Nov. 6, an ACR session will look at how precision medicine research in patients with systemic lupus erythematosus (SLE) has laid groundwork to improve clinical trial design and the implementation of more tailored treatment for SLE and other complex autoimmune diseases.
The first day of the 2-day premeeting course will cover current approaches to studying familial and pediatric rheumatic diseases as well as an outline of how precision medicine could affect treatment approaches to SLE. Later in the day, presentations will focus on examples of personalized medicine approaches that have been derived from studies of cancer genomics and familial syndromes and the genetic underpinning of different responses to medications. The impact of direct-to-consumer genetic testing will also be discussed. Abstract presentations at the end of the day will focus on new genetic biomarkers that differentiate active disease from remission in granulomatosis with polyangiitis and mutations related to cancer-associated myositis.
The second day of the course on Saturday, Nov. 4, will focus on the technology behind precision medicine, followed by data analysis and integration into clinical practice. Technology presentations aim to demonstrate how transcriptional analysis of single immune cells and epigenetics in small numbers of cells can provide information about disease activity and prognosis. Examples of how multiple types of data can be integrated to form a picture of the pathogenesis of diseases such as rheumatoid arthritis will be discussed. Two abstract presentations will serve to show how analysis of tissue-specific serum biomarkers can identify rheumatoid arthritis patients with structural progression and how the presence of a specific antibody can predict better response to anti–tumor necrosis factor treatment and better disease control over time. In the afternoon, sessions will focus on analyzing single-cell data in key cell subpopulations in rheumatic disease and specifically address immune cell interactions across systems in SLE.
On Monday at 1:00 p.m., Maria Virginia Pascual, PhD, director of the Drukier Institute for Children’s Health and the Ronay A. Menschel Professor of Pediatrics at Cornell University in New York will speak in the ACR session, “Precision Medicine for Rheumatic Disease: Closer Than You Think?” Dr. Pascual will provide an overview of her lab’s recent work in transcriptional profiling of pediatric SLE patients, which demonstrates the potential value of immunomonitoring in order to stratify patients into discrete molecular groups to make clinical trial design better and offer more targeted therapies.
FROM ACR 2017
“Great debates” at ACR 2017 address biosimilar switching, new curricular milestones
Two “Great Debates” at this year’s annual meeting of the American College of Rheumatology in San Diego will center on important, but completely separate, issues in rheumatology: whether it is safe to switch to a biosimilar and the relevance of curricular milestones in rheumatology training.
At 2:30 p.m. on Sunday, Nov. 5, a session titled “Biosimilars ... To Switch or Not to Switch? That Is the Question“ will pit Jonathan Kay, MD, against Roy Fleischmann, MD, to try to sway the audience to their point of view in the face of a small evidence base about the consequences of switching.
Dr. Kay, the Timothy S. and Elaine L. Peterson Chair in Rheumatology and professor of medicine at the University of Massachusetts, Worcester, where he directs clinical research in the division of rheumatology, will discuss and defend the usefulness of biosimilars for rheumatoid arthritis in his presentation, “The Data Supports That It Is Safe, Effective and Cost-Effective to Switch to a Biosimilar.” He has been greatly involved in clinical research on the development of biosimilars to treat rheumatic diseases in recent years.
In his presentation, “The Data Is Not Convincing. One Study Cannot Be Generalized to All Indications, and Some Studies Suggest That It Is Not Safe, Not Effective and Not Cost-Effective to Switch All Patients (YET) to a Biosimilar,” Dr. Fleischmann will discuss and defend the position that biosimilars are not yet well-enough researched to confidently allow switching. Dr. Fleischmann is clinical professor in the department of internal medicine at the University of Texas Southwestern Medical Center, Dallas.
At 7:30 a.m. on Monday, Nov. 6, two clinician-educators will advocate for opposing opinions in “The Great (Educational) Debate: Milestones: Meaningful vs. Millstone.” The debate will focus on the relative merits of the Accreditation Council for Graduate Medical Education’s Next Accreditation System, which in 2013 led to a paradigm shift in how training programs approach curriculum development, and how both trainees and their programs are assessed.
Calvin Brown, MD, professor of medicine in the division of rheumatology and director of the rheumatology training program at Northwestern University, Chicago, will describe the reported and perceived benefits of the milestones, while Simon Helfgott, MD, of Brigham and Women’s Hospital, Boston, will summarize the arguments that underlie the call for radical change in the milestones system of evaluation
Two “Great Debates” at this year’s annual meeting of the American College of Rheumatology in San Diego will center on important, but completely separate, issues in rheumatology: whether it is safe to switch to a biosimilar and the relevance of curricular milestones in rheumatology training.
At 2:30 p.m. on Sunday, Nov. 5, a session titled “Biosimilars ... To Switch or Not to Switch? That Is the Question“ will pit Jonathan Kay, MD, against Roy Fleischmann, MD, to try to sway the audience to their point of view in the face of a small evidence base about the consequences of switching.
Dr. Kay, the Timothy S. and Elaine L. Peterson Chair in Rheumatology and professor of medicine at the University of Massachusetts, Worcester, where he directs clinical research in the division of rheumatology, will discuss and defend the usefulness of biosimilars for rheumatoid arthritis in his presentation, “The Data Supports That It Is Safe, Effective and Cost-Effective to Switch to a Biosimilar.” He has been greatly involved in clinical research on the development of biosimilars to treat rheumatic diseases in recent years.
In his presentation, “The Data Is Not Convincing. One Study Cannot Be Generalized to All Indications, and Some Studies Suggest That It Is Not Safe, Not Effective and Not Cost-Effective to Switch All Patients (YET) to a Biosimilar,” Dr. Fleischmann will discuss and defend the position that biosimilars are not yet well-enough researched to confidently allow switching. Dr. Fleischmann is clinical professor in the department of internal medicine at the University of Texas Southwestern Medical Center, Dallas.
At 7:30 a.m. on Monday, Nov. 6, two clinician-educators will advocate for opposing opinions in “The Great (Educational) Debate: Milestones: Meaningful vs. Millstone.” The debate will focus on the relative merits of the Accreditation Council for Graduate Medical Education’s Next Accreditation System, which in 2013 led to a paradigm shift in how training programs approach curriculum development, and how both trainees and their programs are assessed.
Calvin Brown, MD, professor of medicine in the division of rheumatology and director of the rheumatology training program at Northwestern University, Chicago, will describe the reported and perceived benefits of the milestones, while Simon Helfgott, MD, of Brigham and Women’s Hospital, Boston, will summarize the arguments that underlie the call for radical change in the milestones system of evaluation
Two “Great Debates” at this year’s annual meeting of the American College of Rheumatology in San Diego will center on important, but completely separate, issues in rheumatology: whether it is safe to switch to a biosimilar and the relevance of curricular milestones in rheumatology training.
At 2:30 p.m. on Sunday, Nov. 5, a session titled “Biosimilars ... To Switch or Not to Switch? That Is the Question“ will pit Jonathan Kay, MD, against Roy Fleischmann, MD, to try to sway the audience to their point of view in the face of a small evidence base about the consequences of switching.
Dr. Kay, the Timothy S. and Elaine L. Peterson Chair in Rheumatology and professor of medicine at the University of Massachusetts, Worcester, where he directs clinical research in the division of rheumatology, will discuss and defend the usefulness of biosimilars for rheumatoid arthritis in his presentation, “The Data Supports That It Is Safe, Effective and Cost-Effective to Switch to a Biosimilar.” He has been greatly involved in clinical research on the development of biosimilars to treat rheumatic diseases in recent years.
In his presentation, “The Data Is Not Convincing. One Study Cannot Be Generalized to All Indications, and Some Studies Suggest That It Is Not Safe, Not Effective and Not Cost-Effective to Switch All Patients (YET) to a Biosimilar,” Dr. Fleischmann will discuss and defend the position that biosimilars are not yet well-enough researched to confidently allow switching. Dr. Fleischmann is clinical professor in the department of internal medicine at the University of Texas Southwestern Medical Center, Dallas.
At 7:30 a.m. on Monday, Nov. 6, two clinician-educators will advocate for opposing opinions in “The Great (Educational) Debate: Milestones: Meaningful vs. Millstone.” The debate will focus on the relative merits of the Accreditation Council for Graduate Medical Education’s Next Accreditation System, which in 2013 led to a paradigm shift in how training programs approach curriculum development, and how both trainees and their programs are assessed.
Calvin Brown, MD, professor of medicine in the division of rheumatology and director of the rheumatology training program at Northwestern University, Chicago, will describe the reported and perceived benefits of the milestones, while Simon Helfgott, MD, of Brigham and Women’s Hospital, Boston, will summarize the arguments that underlie the call for radical change in the milestones system of evaluation
FROM ACR 2017
Stopping anti-TNF drugs in PsA has high rebound risk
A report on the largest cohort to date of patients with psoriatic arthritis who discontinued tumor necrosis factor inhibitor (TNFi) therapy during a period of low disease activity adds further evidence in support of keeping patients on the biologics during such periods.
The findings from the report on patients with psoriatic arthritis (PsA) from the U.S. Corrona registry found a rebound in disease activity in 69 (73%) of 94 patients. These results are in line with prior small studies, including a pilot, randomized, controlled trial, in PsA patients who have attempted to stop conventional synthetic disease-modifying antirheumatic drugs and biologic DMARDs, mostly TNFi agents, during periods of low disease activity (LDA).
The 73% rate of disease activity rebound observed in the patients – defined by a Clinical Disease Activity Index (CDAI) score of more than 10, a reinitiation of their TNFi, or the start of a new agent – “offers an important perspective for physicians who are considering TNFi discontinuation for patients who have achieved remission/LDA and may provide a key piece of data in discussing the most likely potential outcome with their patients’ TNFi discontinuation,” Dr. Harrold and her associates wrote. “TNFi discontinuation after achieving LDA should be carefully considered.”
The 94 patients with PsA in the Corrona registry study all met study criteria for remission or LDA (CDAI score of 10 or less) and had discontinued their TNFi while in LDA and did not immediately switch to a different biologic. The mean age of the patients was 51; 57% were women and 92% were white. At the time of TNFi initiation, they had an average disease duration of 8.4 years and a mean CDAI score of 10.1, and 64% had LDA. Most patients had taken methotrexate (86%) or a conventional synthetic DMARD (10%) prior to starting a TNFi (J Rheumatol. 2017 Oct 1. doi: 10.3899/jrheum.161567).
Among the 69 patients with rebound of disease activity, 15 had a CDAI score of greater than 10, 24 restarted a biologic DMARD but did not have an elevated CDAI, and 30 had both an elevated CDAI and biologic initiation.
Close to three-quarters of the 59 rebounders who returned for a postrebound visit were in remission or LDA at that visit, and nearly half had resumed use of their original TNFi by the time of the visit.
The U.S.-based Corrona registry has registered about 6,000 PsA patients from around 500 rheumatologists since 2001. The conclusions that can be drawn from the current study, which included patients who started a TNFi between Oct. 1, 2002, and March 21, 2013, are limited by the use of the CDAI, a measure for disease activity in rheumatoid arthritis. The use of the CDAI means that disease features of PsA such as enthesitis, psoriasis, and dactylitis were not captured in the assessment of LDA. “That is a caveat,” Dr. Harrold said.
Other limitations of the study include its sporadic follow-up and the open-label, uncontrolled nature of the TNFi discontinuation, according to Dr. Helliwell.
“There could have been any number of reasons why the drug was stopped, not just because of low disease activity – because of financial reasons, perhaps, adverse events, or ... a switch to another drug,” he said in an interview.
Despite these limitations, Dr. Helliwell said that the study “provides useful data, and it will add to the number of publications on this subject that are already out there, and it is the biggest cohort that’s been published.”
Dr. Harrold and her coauthors said that their findings were consistent with those from other studies, including one that Dr. Helliwell’s group was a part of.
That was a pilot randomized, controlled trial to test the feasibility of drug withdrawal in PsA patients in a stable, low disease state, defined by meeting minimal disease activity criteria. Of the 17 patients randomized, 6 of 11 who were in the withdrawal arm experienced a flare (defined as not meeting minimal disease activity criteria). Of these six patients, two had been receiving methotrexate only and four had been treated with methotrexate plus a biologic, whereas none of the six patients who continued therapy experienced a flare (Clin Rheumatol. 2015;34[8]:1407-12). Dr. Helliwell noted that all patients in the withdrawal arm eventually relapsed.
Another study with similar results from investigators at the University of Erlangen-Nuremberg (Germany) found that out of 26 PsA patients on either methotrexate monotherapy (n = 14) or a TNFi (n = 12), with no musculoskeletal symptoms and minimal skin disease, 20 had disease recurrence at a mean of just 74 days after drug discontinuation (Ann Rheum Dis. 2015;74:655-60).
Investigators for another study from the Corrona registry looked at 325 discontinuations of TNFi therapy while in LDA in 302 PsA patients and found disease rebound in 45% at an estimated median time of about 29 months. This study included a physician’s global assessment of skin psoriasis of 20 or less out of 100 as part of the definition of LDA, in addition to a CDAI score of 10 or less. Current smoking was the only significant predictor of disease rebound in a multivariate analysis. Age, gender, the number of prior TNFis used, or overweight or obese status did not predict disease rebound. CDAI score of 3.2 or greater was just outside the range of statistical significance (RMD Open. 2017;3:e000395).
“I think the message here is: ‘Be very careful discontinuing anti-TNF drugs in people with PsA and low disease activity.’ It’s not the same as rheumatoid arthritis in that respect,” Dr. Helliwell said.
Ultimately, the goal is to determine the characteristics of patients who can either stop or taper drugs such as TNF inhibitors. “I think there are going to be patients who can be tapered off, and there are going to be patients who can’t be,” Dr. Harrold said. Going forward, it will be important to identify which subset of patients are going to flare when taken off medication, such as a TNF inhibitor, particularly because of the diversity of presentations that PsA patients can have, she said.
Dr. Helliwell agreed, saying that, when he is asked whether you can stop a TNFi in PsA patients with LDA, “I say you should taper the drug by increasing the interval between doses or lower the dose, but not discontinue it.”
The Corrona registry has been supported by numerous pharmaceutical companies that manufacture drugs for PsA and rheumatoid arthritis. Dr. Harrold and some of her coinvestigators are employees and shareholders of Corrona. Some authors are employees and shareholders of Amgen, and others reported financial relationships with various pharmaceutical companies. Dr. Helliwell has received grant or research support, consulted for, or served on the speakers bureau for many of the companies that support Corrona.
A report on the largest cohort to date of patients with psoriatic arthritis who discontinued tumor necrosis factor inhibitor (TNFi) therapy during a period of low disease activity adds further evidence in support of keeping patients on the biologics during such periods.
The findings from the report on patients with psoriatic arthritis (PsA) from the U.S. Corrona registry found a rebound in disease activity in 69 (73%) of 94 patients. These results are in line with prior small studies, including a pilot, randomized, controlled trial, in PsA patients who have attempted to stop conventional synthetic disease-modifying antirheumatic drugs and biologic DMARDs, mostly TNFi agents, during periods of low disease activity (LDA).
The 73% rate of disease activity rebound observed in the patients – defined by a Clinical Disease Activity Index (CDAI) score of more than 10, a reinitiation of their TNFi, or the start of a new agent – “offers an important perspective for physicians who are considering TNFi discontinuation for patients who have achieved remission/LDA and may provide a key piece of data in discussing the most likely potential outcome with their patients’ TNFi discontinuation,” Dr. Harrold and her associates wrote. “TNFi discontinuation after achieving LDA should be carefully considered.”
The 94 patients with PsA in the Corrona registry study all met study criteria for remission or LDA (CDAI score of 10 or less) and had discontinued their TNFi while in LDA and did not immediately switch to a different biologic. The mean age of the patients was 51; 57% were women and 92% were white. At the time of TNFi initiation, they had an average disease duration of 8.4 years and a mean CDAI score of 10.1, and 64% had LDA. Most patients had taken methotrexate (86%) or a conventional synthetic DMARD (10%) prior to starting a TNFi (J Rheumatol. 2017 Oct 1. doi: 10.3899/jrheum.161567).
Among the 69 patients with rebound of disease activity, 15 had a CDAI score of greater than 10, 24 restarted a biologic DMARD but did not have an elevated CDAI, and 30 had both an elevated CDAI and biologic initiation.
Close to three-quarters of the 59 rebounders who returned for a postrebound visit were in remission or LDA at that visit, and nearly half had resumed use of their original TNFi by the time of the visit.
The U.S.-based Corrona registry has registered about 6,000 PsA patients from around 500 rheumatologists since 2001. The conclusions that can be drawn from the current study, which included patients who started a TNFi between Oct. 1, 2002, and March 21, 2013, are limited by the use of the CDAI, a measure for disease activity in rheumatoid arthritis. The use of the CDAI means that disease features of PsA such as enthesitis, psoriasis, and dactylitis were not captured in the assessment of LDA. “That is a caveat,” Dr. Harrold said.
Other limitations of the study include its sporadic follow-up and the open-label, uncontrolled nature of the TNFi discontinuation, according to Dr. Helliwell.
“There could have been any number of reasons why the drug was stopped, not just because of low disease activity – because of financial reasons, perhaps, adverse events, or ... a switch to another drug,” he said in an interview.
Despite these limitations, Dr. Helliwell said that the study “provides useful data, and it will add to the number of publications on this subject that are already out there, and it is the biggest cohort that’s been published.”
Dr. Harrold and her coauthors said that their findings were consistent with those from other studies, including one that Dr. Helliwell’s group was a part of.
That was a pilot randomized, controlled trial to test the feasibility of drug withdrawal in PsA patients in a stable, low disease state, defined by meeting minimal disease activity criteria. Of the 17 patients randomized, 6 of 11 who were in the withdrawal arm experienced a flare (defined as not meeting minimal disease activity criteria). Of these six patients, two had been receiving methotrexate only and four had been treated with methotrexate plus a biologic, whereas none of the six patients who continued therapy experienced a flare (Clin Rheumatol. 2015;34[8]:1407-12). Dr. Helliwell noted that all patients in the withdrawal arm eventually relapsed.
Another study with similar results from investigators at the University of Erlangen-Nuremberg (Germany) found that out of 26 PsA patients on either methotrexate monotherapy (n = 14) or a TNFi (n = 12), with no musculoskeletal symptoms and minimal skin disease, 20 had disease recurrence at a mean of just 74 days after drug discontinuation (Ann Rheum Dis. 2015;74:655-60).
Investigators for another study from the Corrona registry looked at 325 discontinuations of TNFi therapy while in LDA in 302 PsA patients and found disease rebound in 45% at an estimated median time of about 29 months. This study included a physician’s global assessment of skin psoriasis of 20 or less out of 100 as part of the definition of LDA, in addition to a CDAI score of 10 or less. Current smoking was the only significant predictor of disease rebound in a multivariate analysis. Age, gender, the number of prior TNFis used, or overweight or obese status did not predict disease rebound. CDAI score of 3.2 or greater was just outside the range of statistical significance (RMD Open. 2017;3:e000395).
“I think the message here is: ‘Be very careful discontinuing anti-TNF drugs in people with PsA and low disease activity.’ It’s not the same as rheumatoid arthritis in that respect,” Dr. Helliwell said.
Ultimately, the goal is to determine the characteristics of patients who can either stop or taper drugs such as TNF inhibitors. “I think there are going to be patients who can be tapered off, and there are going to be patients who can’t be,” Dr. Harrold said. Going forward, it will be important to identify which subset of patients are going to flare when taken off medication, such as a TNF inhibitor, particularly because of the diversity of presentations that PsA patients can have, she said.
Dr. Helliwell agreed, saying that, when he is asked whether you can stop a TNFi in PsA patients with LDA, “I say you should taper the drug by increasing the interval between doses or lower the dose, but not discontinue it.”
The Corrona registry has been supported by numerous pharmaceutical companies that manufacture drugs for PsA and rheumatoid arthritis. Dr. Harrold and some of her coinvestigators are employees and shareholders of Corrona. Some authors are employees and shareholders of Amgen, and others reported financial relationships with various pharmaceutical companies. Dr. Helliwell has received grant or research support, consulted for, or served on the speakers bureau for many of the companies that support Corrona.
A report on the largest cohort to date of patients with psoriatic arthritis who discontinued tumor necrosis factor inhibitor (TNFi) therapy during a period of low disease activity adds further evidence in support of keeping patients on the biologics during such periods.
The findings from the report on patients with psoriatic arthritis (PsA) from the U.S. Corrona registry found a rebound in disease activity in 69 (73%) of 94 patients. These results are in line with prior small studies, including a pilot, randomized, controlled trial, in PsA patients who have attempted to stop conventional synthetic disease-modifying antirheumatic drugs and biologic DMARDs, mostly TNFi agents, during periods of low disease activity (LDA).
The 73% rate of disease activity rebound observed in the patients – defined by a Clinical Disease Activity Index (CDAI) score of more than 10, a reinitiation of their TNFi, or the start of a new agent – “offers an important perspective for physicians who are considering TNFi discontinuation for patients who have achieved remission/LDA and may provide a key piece of data in discussing the most likely potential outcome with their patients’ TNFi discontinuation,” Dr. Harrold and her associates wrote. “TNFi discontinuation after achieving LDA should be carefully considered.”
The 94 patients with PsA in the Corrona registry study all met study criteria for remission or LDA (CDAI score of 10 or less) and had discontinued their TNFi while in LDA and did not immediately switch to a different biologic. The mean age of the patients was 51; 57% were women and 92% were white. At the time of TNFi initiation, they had an average disease duration of 8.4 years and a mean CDAI score of 10.1, and 64% had LDA. Most patients had taken methotrexate (86%) or a conventional synthetic DMARD (10%) prior to starting a TNFi (J Rheumatol. 2017 Oct 1. doi: 10.3899/jrheum.161567).
Among the 69 patients with rebound of disease activity, 15 had a CDAI score of greater than 10, 24 restarted a biologic DMARD but did not have an elevated CDAI, and 30 had both an elevated CDAI and biologic initiation.
Close to three-quarters of the 59 rebounders who returned for a postrebound visit were in remission or LDA at that visit, and nearly half had resumed use of their original TNFi by the time of the visit.
The U.S.-based Corrona registry has registered about 6,000 PsA patients from around 500 rheumatologists since 2001. The conclusions that can be drawn from the current study, which included patients who started a TNFi between Oct. 1, 2002, and March 21, 2013, are limited by the use of the CDAI, a measure for disease activity in rheumatoid arthritis. The use of the CDAI means that disease features of PsA such as enthesitis, psoriasis, and dactylitis were not captured in the assessment of LDA. “That is a caveat,” Dr. Harrold said.
Other limitations of the study include its sporadic follow-up and the open-label, uncontrolled nature of the TNFi discontinuation, according to Dr. Helliwell.
“There could have been any number of reasons why the drug was stopped, not just because of low disease activity – because of financial reasons, perhaps, adverse events, or ... a switch to another drug,” he said in an interview.
Despite these limitations, Dr. Helliwell said that the study “provides useful data, and it will add to the number of publications on this subject that are already out there, and it is the biggest cohort that’s been published.”
Dr. Harrold and her coauthors said that their findings were consistent with those from other studies, including one that Dr. Helliwell’s group was a part of.
That was a pilot randomized, controlled trial to test the feasibility of drug withdrawal in PsA patients in a stable, low disease state, defined by meeting minimal disease activity criteria. Of the 17 patients randomized, 6 of 11 who were in the withdrawal arm experienced a flare (defined as not meeting minimal disease activity criteria). Of these six patients, two had been receiving methotrexate only and four had been treated with methotrexate plus a biologic, whereas none of the six patients who continued therapy experienced a flare (Clin Rheumatol. 2015;34[8]:1407-12). Dr. Helliwell noted that all patients in the withdrawal arm eventually relapsed.
Another study with similar results from investigators at the University of Erlangen-Nuremberg (Germany) found that out of 26 PsA patients on either methotrexate monotherapy (n = 14) or a TNFi (n = 12), with no musculoskeletal symptoms and minimal skin disease, 20 had disease recurrence at a mean of just 74 days after drug discontinuation (Ann Rheum Dis. 2015;74:655-60).
Investigators for another study from the Corrona registry looked at 325 discontinuations of TNFi therapy while in LDA in 302 PsA patients and found disease rebound in 45% at an estimated median time of about 29 months. This study included a physician’s global assessment of skin psoriasis of 20 or less out of 100 as part of the definition of LDA, in addition to a CDAI score of 10 or less. Current smoking was the only significant predictor of disease rebound in a multivariate analysis. Age, gender, the number of prior TNFis used, or overweight or obese status did not predict disease rebound. CDAI score of 3.2 or greater was just outside the range of statistical significance (RMD Open. 2017;3:e000395).
“I think the message here is: ‘Be very careful discontinuing anti-TNF drugs in people with PsA and low disease activity.’ It’s not the same as rheumatoid arthritis in that respect,” Dr. Helliwell said.
Ultimately, the goal is to determine the characteristics of patients who can either stop or taper drugs such as TNF inhibitors. “I think there are going to be patients who can be tapered off, and there are going to be patients who can’t be,” Dr. Harrold said. Going forward, it will be important to identify which subset of patients are going to flare when taken off medication, such as a TNF inhibitor, particularly because of the diversity of presentations that PsA patients can have, she said.
Dr. Helliwell agreed, saying that, when he is asked whether you can stop a TNFi in PsA patients with LDA, “I say you should taper the drug by increasing the interval between doses or lower the dose, but not discontinue it.”
The Corrona registry has been supported by numerous pharmaceutical companies that manufacture drugs for PsA and rheumatoid arthritis. Dr. Harrold and some of her coinvestigators are employees and shareholders of Corrona. Some authors are employees and shareholders of Amgen, and others reported financial relationships with various pharmaceutical companies. Dr. Helliwell has received grant or research support, consulted for, or served on the speakers bureau for many of the companies that support Corrona.
FROM JOURNAL OF RHEUMATOLOGY
Key clinical point:
Major finding: Among 94 patients, 69 (73%) experienced symptom rebound after discontinuing their TNFi therapy.
Data source: The prospective observational Corrona disease registry database of about 6,000 patients with PsA.
Disclosures: The Corrona registry has been supported by numerous pharmaceutical companies that manufacture drugs for PsA and RA. Dr. Harrold and some of her coinvestigators are employees and shareholders of Corrona. Some authors are employees and shareholders of Amgen, and others reported financial relationships with various pharmaceutical companies. Dr. Helliwell has received grant or research support, consulted for, or served on the speakers bureau for many of the companies that support Corrona.
Poverty affects lupus mortality through damage accumulation
The extent of damage caused by lupus appears to be one of the strongest factors that contributes to the higher mortality observed in lupus patients who live in poverty, according to the results of a longitudinal cohort study of patients.
The findings from this analysis of participants in the Lupus Outcomes Study could potentially lead to solutions to reduce mortality of poor patients with systemic lupus erythematosus (SLE) through understanding why they have higher levels of disease damage, said first author Edward Yelin, PhD, of the Philip R. Lee Institute for Health Policy Studies at the University of California, San Francisco, and his colleagues at the university (Arthritis Care Res. 2017 Oct 3. doi: 10.1002/acr.23428).
Previous studies by the researchers have shown that concurrent and persistent poverty are associated with increased damage accumulation, and permanently exiting poverty reduces the level of accumulated damage. Studies by other groups have also revealed that some measures of low socioeconomic status contribute to elevated mortality in patients with SLE. But few studies have explored how poverty leads to increased mortality in SLE patients.
About two-thirds of the patients recruited for the Lupus Outcomes Study, which began in 2003, joined the study through nonclinical sources, such as public service announcements, patient support groups, and word of mouth; the remainder were recruited from academic and community clinical practices. The patients came from 37 states and from urban and rural areas. The investigators contacted participants in annual structured phone interviews that lasted about 45 minutes. The investigators defined poverty as household income at or below 125% of the federal poverty level because most participants were from high-cost urban areas.
The investigators had full information available for 807 of 814 who completed the annual survey in 2009, and these individuals made up the baseline sample for the mortality analysis through 2015. These 807 patients had a mean age of about 50 years and a disease duration of about 17 years; 93% were women, more than one-third were members of racial and ethnic minorities, and 14% met the study’s definition of poverty.
Poor individuals were more likely to be from a racial or ethnic minority (54% vs. 33%), to have a history of smoking (47% vs. 37%, to have a high school education or less (37% vs. 14%), to have never been married (36% vs. 15%), and to have a higher baseline level of disease damage as measured by score on the Brief Index of Lupus Damage (BILD; 2.8 vs. 2.2).
Overall, more poor individuals died during 2009-2015 (12.1% vs. 8.3%), but the difference was not significant. However, the poor died at a mean age of about 50, compared with 64 for individuals who were not poor. Adjustments for age showed that poverty, disease duration, BILD damage score, and having less than a high school education were all associated with higher mortality. But in a full multivariable analysis, only female gender (hazard ratio, 0.43; 95% confidence interval, 0.19-0.94), BILD damage score (1.17/point on 0-18 scale; 95% CI, 1.07-1.29), and physical health status (0.96/point; 95% CI, 0.94-0.98) were significant predictors of subsequent mortality risk, and poverty was no longer a significant predictor of mortality.
While poverty adjusted for age more than doubled the mortality risk (HR, 2.14; 95% CI, 1.18-3.88), much of the association could be attributed to the level of disease damage because once that variable was added to the analysis, poverty was no longer associated with an elevated mortality risk (HR, 1.68; 95% CI, 0.91-3.10). Furthermore, once the investigators took physical and mental health status into account, the risk of mortality associated with poverty was even smaller (HR, 1.20; 95% CI, 0.61-2.36).
“The present analysis indicates that prevention of accumulated damage will attenuate the mortality risk associated with poverty. We know that to achieve the goal of reduced damage requires good medical care in SLE, but that alone is insufficient since medical care accounts for only a small portion of the variance in damage accumulation between the poor and non-poor,” the investigators wrote. “Strategies to reduce disease damage must take into account the provision of high-quality care for the condition as well as the stress associated with poverty and living in neighborhoods with concentrated poverty.”
The research was supported by the Robert Wood Johnson Investigator in Health Policy Award and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
The extent of damage caused by lupus appears to be one of the strongest factors that contributes to the higher mortality observed in lupus patients who live in poverty, according to the results of a longitudinal cohort study of patients.
The findings from this analysis of participants in the Lupus Outcomes Study could potentially lead to solutions to reduce mortality of poor patients with systemic lupus erythematosus (SLE) through understanding why they have higher levels of disease damage, said first author Edward Yelin, PhD, of the Philip R. Lee Institute for Health Policy Studies at the University of California, San Francisco, and his colleagues at the university (Arthritis Care Res. 2017 Oct 3. doi: 10.1002/acr.23428).
Previous studies by the researchers have shown that concurrent and persistent poverty are associated with increased damage accumulation, and permanently exiting poverty reduces the level of accumulated damage. Studies by other groups have also revealed that some measures of low socioeconomic status contribute to elevated mortality in patients with SLE. But few studies have explored how poverty leads to increased mortality in SLE patients.
About two-thirds of the patients recruited for the Lupus Outcomes Study, which began in 2003, joined the study through nonclinical sources, such as public service announcements, patient support groups, and word of mouth; the remainder were recruited from academic and community clinical practices. The patients came from 37 states and from urban and rural areas. The investigators contacted participants in annual structured phone interviews that lasted about 45 minutes. The investigators defined poverty as household income at or below 125% of the federal poverty level because most participants were from high-cost urban areas.
The investigators had full information available for 807 of 814 who completed the annual survey in 2009, and these individuals made up the baseline sample for the mortality analysis through 2015. These 807 patients had a mean age of about 50 years and a disease duration of about 17 years; 93% were women, more than one-third were members of racial and ethnic minorities, and 14% met the study’s definition of poverty.
Poor individuals were more likely to be from a racial or ethnic minority (54% vs. 33%), to have a history of smoking (47% vs. 37%, to have a high school education or less (37% vs. 14%), to have never been married (36% vs. 15%), and to have a higher baseline level of disease damage as measured by score on the Brief Index of Lupus Damage (BILD; 2.8 vs. 2.2).
Overall, more poor individuals died during 2009-2015 (12.1% vs. 8.3%), but the difference was not significant. However, the poor died at a mean age of about 50, compared with 64 for individuals who were not poor. Adjustments for age showed that poverty, disease duration, BILD damage score, and having less than a high school education were all associated with higher mortality. But in a full multivariable analysis, only female gender (hazard ratio, 0.43; 95% confidence interval, 0.19-0.94), BILD damage score (1.17/point on 0-18 scale; 95% CI, 1.07-1.29), and physical health status (0.96/point; 95% CI, 0.94-0.98) were significant predictors of subsequent mortality risk, and poverty was no longer a significant predictor of mortality.
While poverty adjusted for age more than doubled the mortality risk (HR, 2.14; 95% CI, 1.18-3.88), much of the association could be attributed to the level of disease damage because once that variable was added to the analysis, poverty was no longer associated with an elevated mortality risk (HR, 1.68; 95% CI, 0.91-3.10). Furthermore, once the investigators took physical and mental health status into account, the risk of mortality associated with poverty was even smaller (HR, 1.20; 95% CI, 0.61-2.36).
“The present analysis indicates that prevention of accumulated damage will attenuate the mortality risk associated with poverty. We know that to achieve the goal of reduced damage requires good medical care in SLE, but that alone is insufficient since medical care accounts for only a small portion of the variance in damage accumulation between the poor and non-poor,” the investigators wrote. “Strategies to reduce disease damage must take into account the provision of high-quality care for the condition as well as the stress associated with poverty and living in neighborhoods with concentrated poverty.”
The research was supported by the Robert Wood Johnson Investigator in Health Policy Award and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
The extent of damage caused by lupus appears to be one of the strongest factors that contributes to the higher mortality observed in lupus patients who live in poverty, according to the results of a longitudinal cohort study of patients.
The findings from this analysis of participants in the Lupus Outcomes Study could potentially lead to solutions to reduce mortality of poor patients with systemic lupus erythematosus (SLE) through understanding why they have higher levels of disease damage, said first author Edward Yelin, PhD, of the Philip R. Lee Institute for Health Policy Studies at the University of California, San Francisco, and his colleagues at the university (Arthritis Care Res. 2017 Oct 3. doi: 10.1002/acr.23428).
Previous studies by the researchers have shown that concurrent and persistent poverty are associated with increased damage accumulation, and permanently exiting poverty reduces the level of accumulated damage. Studies by other groups have also revealed that some measures of low socioeconomic status contribute to elevated mortality in patients with SLE. But few studies have explored how poverty leads to increased mortality in SLE patients.
About two-thirds of the patients recruited for the Lupus Outcomes Study, which began in 2003, joined the study through nonclinical sources, such as public service announcements, patient support groups, and word of mouth; the remainder were recruited from academic and community clinical practices. The patients came from 37 states and from urban and rural areas. The investigators contacted participants in annual structured phone interviews that lasted about 45 minutes. The investigators defined poverty as household income at or below 125% of the federal poverty level because most participants were from high-cost urban areas.
The investigators had full information available for 807 of 814 who completed the annual survey in 2009, and these individuals made up the baseline sample for the mortality analysis through 2015. These 807 patients had a mean age of about 50 years and a disease duration of about 17 years; 93% were women, more than one-third were members of racial and ethnic minorities, and 14% met the study’s definition of poverty.
Poor individuals were more likely to be from a racial or ethnic minority (54% vs. 33%), to have a history of smoking (47% vs. 37%, to have a high school education or less (37% vs. 14%), to have never been married (36% vs. 15%), and to have a higher baseline level of disease damage as measured by score on the Brief Index of Lupus Damage (BILD; 2.8 vs. 2.2).
Overall, more poor individuals died during 2009-2015 (12.1% vs. 8.3%), but the difference was not significant. However, the poor died at a mean age of about 50, compared with 64 for individuals who were not poor. Adjustments for age showed that poverty, disease duration, BILD damage score, and having less than a high school education were all associated with higher mortality. But in a full multivariable analysis, only female gender (hazard ratio, 0.43; 95% confidence interval, 0.19-0.94), BILD damage score (1.17/point on 0-18 scale; 95% CI, 1.07-1.29), and physical health status (0.96/point; 95% CI, 0.94-0.98) were significant predictors of subsequent mortality risk, and poverty was no longer a significant predictor of mortality.
While poverty adjusted for age more than doubled the mortality risk (HR, 2.14; 95% CI, 1.18-3.88), much of the association could be attributed to the level of disease damage because once that variable was added to the analysis, poverty was no longer associated with an elevated mortality risk (HR, 1.68; 95% CI, 0.91-3.10). Furthermore, once the investigators took physical and mental health status into account, the risk of mortality associated with poverty was even smaller (HR, 1.20; 95% CI, 0.61-2.36).
“The present analysis indicates that prevention of accumulated damage will attenuate the mortality risk associated with poverty. We know that to achieve the goal of reduced damage requires good medical care in SLE, but that alone is insufficient since medical care accounts for only a small portion of the variance in damage accumulation between the poor and non-poor,” the investigators wrote. “Strategies to reduce disease damage must take into account the provision of high-quality care for the condition as well as the stress associated with poverty and living in neighborhoods with concentrated poverty.”
The research was supported by the Robert Wood Johnson Investigator in Health Policy Award and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point:
Major finding: Poverty adjusted for age more than doubled the mortality risk (HR, 2.14; 95% CI, 1.18-3.88), but poverty was no longer associated with an elevated mortality risk when level of damage was added (HR, 1.68; 95% CI, 0.91-3.10).
Data source: A total of 807 participants in the Lupus Outcomes Study.
Disclosures: The research was supported by the Robert Wood Johnson Investigator in Health Policy Award and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Plenary sessions at ANA 2017 cover wide spectrum of neurologic topics
The six plenary sessions of the annual meeting of the American Neurological Association, taking place Oct. 15-17 in San Diego, promise to cover a broad range of research areas, including neuronal circuits and behavior, global neurology, precision medicine, antisense oligonucleotide therapies, and molecular imaging.
The morning of Oct. 15 starts off with the plenary session, “Linking Circuits to Behavior: Promise & Peril,” which seeks to impart how technologies such as optogenetics enable manipulation of discrete neural populations but require careful consideration of the methods for interpreting the resulting data in order to translate it to human functional neuroimaging for potential therapeutic use.
Later, in the afternoon of Oct. 15, the traditional Derek Denny-Brown Young Neurological Scholar Symposium will showcase the presentations from the two clinical science winners and one basic science winner of the Derek Denny-Brown Young Neurological Scholar Awards, as well as the 2017 Distinguished Neurology Teacher Award, the 2017 Grass Foundation ANA Award in Neuroscience, and the 2017 Wolfe Neuropathy Research Prize. The Derek Denny-Brown Young Neurological Scholar Award recognizes neurologists and neuroscientists in the first 10 years of their career at the assistant/associate faculty (equivalent) level who have made outstanding basic and clinical scientific advances toward the prevention, diagnosis, treatment, and cure of neurologic diseases. This year, award winner Keven N. Sheth, MD, of Yale University, New Haven, Conn., will present on “Instructive, Pragmatic, and Successful Trials in Acute Brain Injury: Making Intracerebral Hemorrhage the LEAST Devastating Form of Stroke”; Leslie E. Skolarus, MD, of the University of Michigan, Ann Arbor, will present on “Reducing the Burden of Stroke in a Disadvantaged Community”; and Conrad Chris Weihl, MD, PhD, of Washington University in St. Louis will present on “Connecting Protein Quality Control Pathways in Skeletal Muscle and Muscle Disease.” The 2017 Distinguished Neurology Teacher Award goes to Zachary Nathaniel London, MD, of the University of Michigan, Ann Arbor. The winner of this year’s Grass Foundation ANA Award in Neuroscience, which goes to an outstanding young physician-scientist conducting research in basic or clinical neuroscience, is Clotilde Lagier-Tourenne, MD, PhD, of Massachusetts General Hospital, Boston, who will discuss “Modeling C9ORF72 Disease: A Crucial Step for Therapeutic Development in ALS and Frontotemporal Dementia.” The symposium’s final presentation will have Stefanie Geisler, MD, of Washington University in St. Louis, talk about “Targeting a Core Axonal Degeneration Program to Treat Vincristine and Bortezomib-Induced Axonal Degeneration.” Dr. Geisler won the Wolfe Neuropathy Research Prize, which honors outstanding investigators who identify a new cause or treatment of axonal peripheral neuropathy.
The morning plenary session on Oct. 16 will focus on translational neuroscience efforts that are paying off with discoveries and insights into neurologic disorders that have higher prevalence or greater relevance to low- and middle-income countries. Presentations on these efforts will include discussion of the causation and prevention of Konzo, a distinct upper–motor neuron disease associated with cassava cyanogenic poisoning in sub-Saharan Africa; a case-control study on the impact of multiple mycotoxins on the development of Nodding syndrome in northern Uganda; efforts to address neurologic manifestations of sexually transmitted virus infections in Peru; a longitudinal cohort study of neurologic sequelae in Ebola virus disease survivors in Liberia; efforts to protect against cerebral malaria; the epidemiology of peripheral neuropathy in urban and rural Bangladeshi type 2 diabetes patients; and the use of smartphones and teleconsultations to improve care for people with epilepsy in low- and middle-income countries.
“Precision Medicine in Neurologic Disease” is the theme of four presentations in the afternoon plenary session on Oct. 16. Huda Y. Zoghbi, MD, of Baylor University, and Texas Children’s Hospital in Houston will talk about how her work in animal models of disease has enabled new insights into the effect that certain regulator proteins have on levels of disease-driving proteins such as tau and alpha-synuclein in neurodegenerative diseases. Amy Wagers, PhD, of Harvard Medical School, Boston, will describe her lab’s use of the gene-editing potential of the CRISPR-Cas9 system to fix frame-disrupting mutations in the Duchenne muscular dystrophy gene, DMD, which encodes dystrophin, and produce functional dystrophin expression in muscle stem cells in a mouse model of the disease, which partially recovered functional deficiencies of dystrophic muscle. Donald Berry, PhD, of the University of Texas, M.D. Anderson Cancer Center in Houston plans to discuss the importance of adaptive platform trials – which match therapies to patients – from oncology to neurologic therapy trials and the lessons learned from two major ongoing oncology treatment trials. Cristina Sampaio, MD, PhD, of the CHDI Foundation, aims to inform attendees of the power of prognostic and predictive biomarker-guided trials in neurology to improve the likelihood of success of drug development. Three high-scoring abstracts in the field of precision medicine also will be presented.
The final day of the meeting brings a morning plenary session on “Antisense Oligonucleotide Treatment of Genetic Neurological Diseases” that will focus on the use of antisense oligonucleotides (ASOs) to silence specific genes or alter their pre-mRNA splicing in Duchenne muscular dystrophy, spinal muscular atrophy, Huntington’s disease, amyotrophic lateral sclerosis, and tauopathies. Additional presentations will focus on abstracts about blood and salivary biomarkers in Huntington’s disease and the early efficacy and safety results of an ASO in patients with hereditary transthyretin amyloidosis with polyneuropathy.
The expanding use and development of methods to assess brain pathology in vivo sets the scene for the meeting’s final plenary session, “Molecular Imaging in Neurologic Disease” in the afternoon of Oct. 17. The use of positron emission tomography and single-photon emission computed tomography (SPECT) tracers for glucose metabolism, the dopamine system, amyloid-beta, tau, synaptic markers, and activated microglia has grown substantially to investigate disease mechanisms, develop new therapeutics, and provide diagnostic and prognostic clinical care. Reisa Sperling, MD, of Harvard Medical School, Boston, will provide an overview of the direction of PET ligand use and development in diagnosing early Alzheimer’s disease. Nicolaas I. Bohnen, MD, PhD, of the University of Michigan, Ann Arbor, will describe a hypothesis for how hypercholinergic activity in the brain of Parkinson’s disease patients may for a time compensate for the loss of striatal dopamine and influence the appearance of a tremor-predominant motor phenotype in patients. Richard E. Carson, PhD, of Yale University will focus on the development of PET ligands to monitor synaptic density loss in neuropsychiatric disorders. Noninvasive imaging has also begun to influence research in the detection of neuroinflammation in a wide variety of conditions, with most research focusing on tracers for activated microglia and astrocytes, according to speaker Martin Pomper, MD, PhD, of Johns Hopkins University, Baltimore. The session will conclude with three molecular imaging abstract presentations.
The six plenary sessions of the annual meeting of the American Neurological Association, taking place Oct. 15-17 in San Diego, promise to cover a broad range of research areas, including neuronal circuits and behavior, global neurology, precision medicine, antisense oligonucleotide therapies, and molecular imaging.
The morning of Oct. 15 starts off with the plenary session, “Linking Circuits to Behavior: Promise & Peril,” which seeks to impart how technologies such as optogenetics enable manipulation of discrete neural populations but require careful consideration of the methods for interpreting the resulting data in order to translate it to human functional neuroimaging for potential therapeutic use.
Later, in the afternoon of Oct. 15, the traditional Derek Denny-Brown Young Neurological Scholar Symposium will showcase the presentations from the two clinical science winners and one basic science winner of the Derek Denny-Brown Young Neurological Scholar Awards, as well as the 2017 Distinguished Neurology Teacher Award, the 2017 Grass Foundation ANA Award in Neuroscience, and the 2017 Wolfe Neuropathy Research Prize. The Derek Denny-Brown Young Neurological Scholar Award recognizes neurologists and neuroscientists in the first 10 years of their career at the assistant/associate faculty (equivalent) level who have made outstanding basic and clinical scientific advances toward the prevention, diagnosis, treatment, and cure of neurologic diseases. This year, award winner Keven N. Sheth, MD, of Yale University, New Haven, Conn., will present on “Instructive, Pragmatic, and Successful Trials in Acute Brain Injury: Making Intracerebral Hemorrhage the LEAST Devastating Form of Stroke”; Leslie E. Skolarus, MD, of the University of Michigan, Ann Arbor, will present on “Reducing the Burden of Stroke in a Disadvantaged Community”; and Conrad Chris Weihl, MD, PhD, of Washington University in St. Louis will present on “Connecting Protein Quality Control Pathways in Skeletal Muscle and Muscle Disease.” The 2017 Distinguished Neurology Teacher Award goes to Zachary Nathaniel London, MD, of the University of Michigan, Ann Arbor. The winner of this year’s Grass Foundation ANA Award in Neuroscience, which goes to an outstanding young physician-scientist conducting research in basic or clinical neuroscience, is Clotilde Lagier-Tourenne, MD, PhD, of Massachusetts General Hospital, Boston, who will discuss “Modeling C9ORF72 Disease: A Crucial Step for Therapeutic Development in ALS and Frontotemporal Dementia.” The symposium’s final presentation will have Stefanie Geisler, MD, of Washington University in St. Louis, talk about “Targeting a Core Axonal Degeneration Program to Treat Vincristine and Bortezomib-Induced Axonal Degeneration.” Dr. Geisler won the Wolfe Neuropathy Research Prize, which honors outstanding investigators who identify a new cause or treatment of axonal peripheral neuropathy.
The morning plenary session on Oct. 16 will focus on translational neuroscience efforts that are paying off with discoveries and insights into neurologic disorders that have higher prevalence or greater relevance to low- and middle-income countries. Presentations on these efforts will include discussion of the causation and prevention of Konzo, a distinct upper–motor neuron disease associated with cassava cyanogenic poisoning in sub-Saharan Africa; a case-control study on the impact of multiple mycotoxins on the development of Nodding syndrome in northern Uganda; efforts to address neurologic manifestations of sexually transmitted virus infections in Peru; a longitudinal cohort study of neurologic sequelae in Ebola virus disease survivors in Liberia; efforts to protect against cerebral malaria; the epidemiology of peripheral neuropathy in urban and rural Bangladeshi type 2 diabetes patients; and the use of smartphones and teleconsultations to improve care for people with epilepsy in low- and middle-income countries.
“Precision Medicine in Neurologic Disease” is the theme of four presentations in the afternoon plenary session on Oct. 16. Huda Y. Zoghbi, MD, of Baylor University, and Texas Children’s Hospital in Houston will talk about how her work in animal models of disease has enabled new insights into the effect that certain regulator proteins have on levels of disease-driving proteins such as tau and alpha-synuclein in neurodegenerative diseases. Amy Wagers, PhD, of Harvard Medical School, Boston, will describe her lab’s use of the gene-editing potential of the CRISPR-Cas9 system to fix frame-disrupting mutations in the Duchenne muscular dystrophy gene, DMD, which encodes dystrophin, and produce functional dystrophin expression in muscle stem cells in a mouse model of the disease, which partially recovered functional deficiencies of dystrophic muscle. Donald Berry, PhD, of the University of Texas, M.D. Anderson Cancer Center in Houston plans to discuss the importance of adaptive platform trials – which match therapies to patients – from oncology to neurologic therapy trials and the lessons learned from two major ongoing oncology treatment trials. Cristina Sampaio, MD, PhD, of the CHDI Foundation, aims to inform attendees of the power of prognostic and predictive biomarker-guided trials in neurology to improve the likelihood of success of drug development. Three high-scoring abstracts in the field of precision medicine also will be presented.
The final day of the meeting brings a morning plenary session on “Antisense Oligonucleotide Treatment of Genetic Neurological Diseases” that will focus on the use of antisense oligonucleotides (ASOs) to silence specific genes or alter their pre-mRNA splicing in Duchenne muscular dystrophy, spinal muscular atrophy, Huntington’s disease, amyotrophic lateral sclerosis, and tauopathies. Additional presentations will focus on abstracts about blood and salivary biomarkers in Huntington’s disease and the early efficacy and safety results of an ASO in patients with hereditary transthyretin amyloidosis with polyneuropathy.
The expanding use and development of methods to assess brain pathology in vivo sets the scene for the meeting’s final plenary session, “Molecular Imaging in Neurologic Disease” in the afternoon of Oct. 17. The use of positron emission tomography and single-photon emission computed tomography (SPECT) tracers for glucose metabolism, the dopamine system, amyloid-beta, tau, synaptic markers, and activated microglia has grown substantially to investigate disease mechanisms, develop new therapeutics, and provide diagnostic and prognostic clinical care. Reisa Sperling, MD, of Harvard Medical School, Boston, will provide an overview of the direction of PET ligand use and development in diagnosing early Alzheimer’s disease. Nicolaas I. Bohnen, MD, PhD, of the University of Michigan, Ann Arbor, will describe a hypothesis for how hypercholinergic activity in the brain of Parkinson’s disease patients may for a time compensate for the loss of striatal dopamine and influence the appearance of a tremor-predominant motor phenotype in patients. Richard E. Carson, PhD, of Yale University will focus on the development of PET ligands to monitor synaptic density loss in neuropsychiatric disorders. Noninvasive imaging has also begun to influence research in the detection of neuroinflammation in a wide variety of conditions, with most research focusing on tracers for activated microglia and astrocytes, according to speaker Martin Pomper, MD, PhD, of Johns Hopkins University, Baltimore. The session will conclude with three molecular imaging abstract presentations.
The six plenary sessions of the annual meeting of the American Neurological Association, taking place Oct. 15-17 in San Diego, promise to cover a broad range of research areas, including neuronal circuits and behavior, global neurology, precision medicine, antisense oligonucleotide therapies, and molecular imaging.
The morning of Oct. 15 starts off with the plenary session, “Linking Circuits to Behavior: Promise & Peril,” which seeks to impart how technologies such as optogenetics enable manipulation of discrete neural populations but require careful consideration of the methods for interpreting the resulting data in order to translate it to human functional neuroimaging for potential therapeutic use.
Later, in the afternoon of Oct. 15, the traditional Derek Denny-Brown Young Neurological Scholar Symposium will showcase the presentations from the two clinical science winners and one basic science winner of the Derek Denny-Brown Young Neurological Scholar Awards, as well as the 2017 Distinguished Neurology Teacher Award, the 2017 Grass Foundation ANA Award in Neuroscience, and the 2017 Wolfe Neuropathy Research Prize. The Derek Denny-Brown Young Neurological Scholar Award recognizes neurologists and neuroscientists in the first 10 years of their career at the assistant/associate faculty (equivalent) level who have made outstanding basic and clinical scientific advances toward the prevention, diagnosis, treatment, and cure of neurologic diseases. This year, award winner Keven N. Sheth, MD, of Yale University, New Haven, Conn., will present on “Instructive, Pragmatic, and Successful Trials in Acute Brain Injury: Making Intracerebral Hemorrhage the LEAST Devastating Form of Stroke”; Leslie E. Skolarus, MD, of the University of Michigan, Ann Arbor, will present on “Reducing the Burden of Stroke in a Disadvantaged Community”; and Conrad Chris Weihl, MD, PhD, of Washington University in St. Louis will present on “Connecting Protein Quality Control Pathways in Skeletal Muscle and Muscle Disease.” The 2017 Distinguished Neurology Teacher Award goes to Zachary Nathaniel London, MD, of the University of Michigan, Ann Arbor. The winner of this year’s Grass Foundation ANA Award in Neuroscience, which goes to an outstanding young physician-scientist conducting research in basic or clinical neuroscience, is Clotilde Lagier-Tourenne, MD, PhD, of Massachusetts General Hospital, Boston, who will discuss “Modeling C9ORF72 Disease: A Crucial Step for Therapeutic Development in ALS and Frontotemporal Dementia.” The symposium’s final presentation will have Stefanie Geisler, MD, of Washington University in St. Louis, talk about “Targeting a Core Axonal Degeneration Program to Treat Vincristine and Bortezomib-Induced Axonal Degeneration.” Dr. Geisler won the Wolfe Neuropathy Research Prize, which honors outstanding investigators who identify a new cause or treatment of axonal peripheral neuropathy.
The morning plenary session on Oct. 16 will focus on translational neuroscience efforts that are paying off with discoveries and insights into neurologic disorders that have higher prevalence or greater relevance to low- and middle-income countries. Presentations on these efforts will include discussion of the causation and prevention of Konzo, a distinct upper–motor neuron disease associated with cassava cyanogenic poisoning in sub-Saharan Africa; a case-control study on the impact of multiple mycotoxins on the development of Nodding syndrome in northern Uganda; efforts to address neurologic manifestations of sexually transmitted virus infections in Peru; a longitudinal cohort study of neurologic sequelae in Ebola virus disease survivors in Liberia; efforts to protect against cerebral malaria; the epidemiology of peripheral neuropathy in urban and rural Bangladeshi type 2 diabetes patients; and the use of smartphones and teleconsultations to improve care for people with epilepsy in low- and middle-income countries.
“Precision Medicine in Neurologic Disease” is the theme of four presentations in the afternoon plenary session on Oct. 16. Huda Y. Zoghbi, MD, of Baylor University, and Texas Children’s Hospital in Houston will talk about how her work in animal models of disease has enabled new insights into the effect that certain regulator proteins have on levels of disease-driving proteins such as tau and alpha-synuclein in neurodegenerative diseases. Amy Wagers, PhD, of Harvard Medical School, Boston, will describe her lab’s use of the gene-editing potential of the CRISPR-Cas9 system to fix frame-disrupting mutations in the Duchenne muscular dystrophy gene, DMD, which encodes dystrophin, and produce functional dystrophin expression in muscle stem cells in a mouse model of the disease, which partially recovered functional deficiencies of dystrophic muscle. Donald Berry, PhD, of the University of Texas, M.D. Anderson Cancer Center in Houston plans to discuss the importance of adaptive platform trials – which match therapies to patients – from oncology to neurologic therapy trials and the lessons learned from two major ongoing oncology treatment trials. Cristina Sampaio, MD, PhD, of the CHDI Foundation, aims to inform attendees of the power of prognostic and predictive biomarker-guided trials in neurology to improve the likelihood of success of drug development. Three high-scoring abstracts in the field of precision medicine also will be presented.
The final day of the meeting brings a morning plenary session on “Antisense Oligonucleotide Treatment of Genetic Neurological Diseases” that will focus on the use of antisense oligonucleotides (ASOs) to silence specific genes or alter their pre-mRNA splicing in Duchenne muscular dystrophy, spinal muscular atrophy, Huntington’s disease, amyotrophic lateral sclerosis, and tauopathies. Additional presentations will focus on abstracts about blood and salivary biomarkers in Huntington’s disease and the early efficacy and safety results of an ASO in patients with hereditary transthyretin amyloidosis with polyneuropathy.
The expanding use and development of methods to assess brain pathology in vivo sets the scene for the meeting’s final plenary session, “Molecular Imaging in Neurologic Disease” in the afternoon of Oct. 17. The use of positron emission tomography and single-photon emission computed tomography (SPECT) tracers for glucose metabolism, the dopamine system, amyloid-beta, tau, synaptic markers, and activated microglia has grown substantially to investigate disease mechanisms, develop new therapeutics, and provide diagnostic and prognostic clinical care. Reisa Sperling, MD, of Harvard Medical School, Boston, will provide an overview of the direction of PET ligand use and development in diagnosing early Alzheimer’s disease. Nicolaas I. Bohnen, MD, PhD, of the University of Michigan, Ann Arbor, will describe a hypothesis for how hypercholinergic activity in the brain of Parkinson’s disease patients may for a time compensate for the loss of striatal dopamine and influence the appearance of a tremor-predominant motor phenotype in patients. Richard E. Carson, PhD, of Yale University will focus on the development of PET ligands to monitor synaptic density loss in neuropsychiatric disorders. Noninvasive imaging has also begun to influence research in the detection of neuroinflammation in a wide variety of conditions, with most research focusing on tracers for activated microglia and astrocytes, according to speaker Martin Pomper, MD, PhD, of Johns Hopkins University, Baltimore. The session will conclude with three molecular imaging abstract presentations.
BRAIN Initiative update to whet appetite for main ANA meeting
Before the main American Neurological Association annual meeting begins in San Diego, plan on attending a special premeeting symposium, “Big Science and the BRAIN Initiative,” on the evening of Saturday, Oct. 14, to learn what a panel of experts has to say about the project, which is now entering its 4th year.
The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is aimed at supporting the development of an arsenal of new tools, multiscale maps, and new knowledge of neural circuits in both health and disease.
Walter Koroshetz, MD, director of the National Institute of Neurological Disorders and Stroke, Bethesda, Md., will chair the symposium and describe the structure of the initiative and its seven high-level research priorities.
Arnold Kriegstein, MD, PhD, of the University of California, San Francisco, will describe his research groups’ efforts at using single-cell approaches to establish an integrative definition of cell types in the developing human neocortex.
Viviana Gradinaru, PhD, of the California Institute of Technology, Pasadena, plans to provide insight on how her lab has developed safe, efficient, and specific vectors for targeting specific cells in the brain to learn about the circuits underlying locomotion, reward, and sleep, and to report on their activity history.
Sydney Cash, MD, PhD, of Massachusetts General Hospital, Boston, aims to survey the history and current landscape of available approaches toward obtaining single-neuron level information from patients, and to describe how this level of precision complements both meso- and macroscale information. He will describe how the huge amount of information being generated from these approaches is being examined with “big data” analytics.
Anna Devor, PhD, of the University of California, San Diego, intends to illustrate a “bottom-up” forward model for how to bridge the mechanistic insights we have gleaned from animal models and match them to noninvasive human neuroimaging data from functional MRI, functional near-infrared spectroscopy, magneto/electroencephalography, and positron emission tomography. This would involve identifying the noninvasive imaging signatures of specific neuronal cell types in order to derive better tools and techniques for estimating neuronal activity from multimodal noninvasive imaging data.
Before the main American Neurological Association annual meeting begins in San Diego, plan on attending a special premeeting symposium, “Big Science and the BRAIN Initiative,” on the evening of Saturday, Oct. 14, to learn what a panel of experts has to say about the project, which is now entering its 4th year.
The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is aimed at supporting the development of an arsenal of new tools, multiscale maps, and new knowledge of neural circuits in both health and disease.
Walter Koroshetz, MD, director of the National Institute of Neurological Disorders and Stroke, Bethesda, Md., will chair the symposium and describe the structure of the initiative and its seven high-level research priorities.
Arnold Kriegstein, MD, PhD, of the University of California, San Francisco, will describe his research groups’ efforts at using single-cell approaches to establish an integrative definition of cell types in the developing human neocortex.
Viviana Gradinaru, PhD, of the California Institute of Technology, Pasadena, plans to provide insight on how her lab has developed safe, efficient, and specific vectors for targeting specific cells in the brain to learn about the circuits underlying locomotion, reward, and sleep, and to report on their activity history.
Sydney Cash, MD, PhD, of Massachusetts General Hospital, Boston, aims to survey the history and current landscape of available approaches toward obtaining single-neuron level information from patients, and to describe how this level of precision complements both meso- and macroscale information. He will describe how the huge amount of information being generated from these approaches is being examined with “big data” analytics.
Anna Devor, PhD, of the University of California, San Diego, intends to illustrate a “bottom-up” forward model for how to bridge the mechanistic insights we have gleaned from animal models and match them to noninvasive human neuroimaging data from functional MRI, functional near-infrared spectroscopy, magneto/electroencephalography, and positron emission tomography. This would involve identifying the noninvasive imaging signatures of specific neuronal cell types in order to derive better tools and techniques for estimating neuronal activity from multimodal noninvasive imaging data.
Before the main American Neurological Association annual meeting begins in San Diego, plan on attending a special premeeting symposium, “Big Science and the BRAIN Initiative,” on the evening of Saturday, Oct. 14, to learn what a panel of experts has to say about the project, which is now entering its 4th year.
The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is aimed at supporting the development of an arsenal of new tools, multiscale maps, and new knowledge of neural circuits in both health and disease.
Walter Koroshetz, MD, director of the National Institute of Neurological Disorders and Stroke, Bethesda, Md., will chair the symposium and describe the structure of the initiative and its seven high-level research priorities.
Arnold Kriegstein, MD, PhD, of the University of California, San Francisco, will describe his research groups’ efforts at using single-cell approaches to establish an integrative definition of cell types in the developing human neocortex.
Viviana Gradinaru, PhD, of the California Institute of Technology, Pasadena, plans to provide insight on how her lab has developed safe, efficient, and specific vectors for targeting specific cells in the brain to learn about the circuits underlying locomotion, reward, and sleep, and to report on their activity history.
Sydney Cash, MD, PhD, of Massachusetts General Hospital, Boston, aims to survey the history and current landscape of available approaches toward obtaining single-neuron level information from patients, and to describe how this level of precision complements both meso- and macroscale information. He will describe how the huge amount of information being generated from these approaches is being examined with “big data” analytics.
Anna Devor, PhD, of the University of California, San Diego, intends to illustrate a “bottom-up” forward model for how to bridge the mechanistic insights we have gleaned from animal models and match them to noninvasive human neuroimaging data from functional MRI, functional near-infrared spectroscopy, magneto/electroencephalography, and positron emission tomography. This would involve identifying the noninvasive imaging signatures of specific neuronal cell types in order to derive better tools and techniques for estimating neuronal activity from multimodal noninvasive imaging data.
ANA 2017 offers career development sessions at all levels
Professional developments courses that will take place each morning during the annual meeting of the American Neurological Association in San Diego offer special opportunities to learn about the rewards and challenges of different career options for neurologists and researchers in academic neurology from those who have gone down a variety of careers paths themselves. Three courses each morning are geared specifically for students, residents, post-docs, and fellows, as well as for professionals at early-, mid-, and university-chair career levels.
For students, residents, post-docs, and fellows
On Oct. 15, young neurology scholars will begin the course with a discussion on the transition from neurology resident to fellow, and then career pathways as a basic scientist, a clinical scientist/researcher, and clinician-administrator. Last year’s recipients of the Derek Denny-Brown Young Neurological Scholar Award also will provide insights on successful early careers in academic neurology.
Global Health has many opportunities for individuals who are looking at potential career paths in neurology to conduct research, clinical care, or educate others in low- to middle-income countries. Speakers on Oct. 16 will share their experiences and discuss emerging trends in global health in neurology and ways in which individuals might pursue careers or opportunities that complement pursuits in academic neurology.
A workshop on Oct. 17 will focus on the essential skills needed for a successful job-seeking experience in academic neurology. There will be opportunities to practice interviewing and negotiating skills, as well as to learn how to market your research and abilities when the opportunity strikes and time is limited.
For early- to mid-career levels
Finding a niche and a successful career trajectory takes a good deal of planning and taking opportunities when the time is right. On Oct. 15, several mid-career level academic neurologists will share their career trajectories and alternative methods they have used for obtaining support and funding for their clinical research, educational enterprises, and curricular development.
The Oct. 16 career development course will outline methods for setting milestones for career development and finding the resources and mentoring individuals you will need for career advancement.
To learn skills and discover tools that will help to write successful grant proposals, particularly for the National Institutes of Health, come to the session on Oct. 17. You can learn how to develop your grant application, respond to critiques of your application, and hear about a variety of sources of funding.
For university chairs of neurology
At a time in which funding for salaries is hampered by many factors, salary disparities are changing across subspecialties as well as in different faculty positions, with some disparities widening and others shrinking. Come to the career development course on Oct. 15 to learn about novel revenue sources and ways in which you can best subsidize the salaries of faculties in your department as well as offer nonmonetary compensation.
Given the current uncertainties of the fates of Affordable Care Act, Medicare, and other major systems supporting health care, it is important to know the best approach to take in advocating for academic neurology and your department’s needs. At the course on Oct. 16, come learn about current health policy issues and the political climate and determine how and when to be politically active.
To understand the impact that the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) requirements will have on academic neurology, come to the session on Oct. 17. You’ll learn how population health measures and value-based care can be brought into an academic neurology practice, how to report on quality measures in the Merit-based Incentive Payment System, and how to participate in Advanced Alternative Payment Models.
Professional developments courses that will take place each morning during the annual meeting of the American Neurological Association in San Diego offer special opportunities to learn about the rewards and challenges of different career options for neurologists and researchers in academic neurology from those who have gone down a variety of careers paths themselves. Three courses each morning are geared specifically for students, residents, post-docs, and fellows, as well as for professionals at early-, mid-, and university-chair career levels.
For students, residents, post-docs, and fellows
On Oct. 15, young neurology scholars will begin the course with a discussion on the transition from neurology resident to fellow, and then career pathways as a basic scientist, a clinical scientist/researcher, and clinician-administrator. Last year’s recipients of the Derek Denny-Brown Young Neurological Scholar Award also will provide insights on successful early careers in academic neurology.
Global Health has many opportunities for individuals who are looking at potential career paths in neurology to conduct research, clinical care, or educate others in low- to middle-income countries. Speakers on Oct. 16 will share their experiences and discuss emerging trends in global health in neurology and ways in which individuals might pursue careers or opportunities that complement pursuits in academic neurology.
A workshop on Oct. 17 will focus on the essential skills needed for a successful job-seeking experience in academic neurology. There will be opportunities to practice interviewing and negotiating skills, as well as to learn how to market your research and abilities when the opportunity strikes and time is limited.
For early- to mid-career levels
Finding a niche and a successful career trajectory takes a good deal of planning and taking opportunities when the time is right. On Oct. 15, several mid-career level academic neurologists will share their career trajectories and alternative methods they have used for obtaining support and funding for their clinical research, educational enterprises, and curricular development.
The Oct. 16 career development course will outline methods for setting milestones for career development and finding the resources and mentoring individuals you will need for career advancement.
To learn skills and discover tools that will help to write successful grant proposals, particularly for the National Institutes of Health, come to the session on Oct. 17. You can learn how to develop your grant application, respond to critiques of your application, and hear about a variety of sources of funding.
For university chairs of neurology
At a time in which funding for salaries is hampered by many factors, salary disparities are changing across subspecialties as well as in different faculty positions, with some disparities widening and others shrinking. Come to the career development course on Oct. 15 to learn about novel revenue sources and ways in which you can best subsidize the salaries of faculties in your department as well as offer nonmonetary compensation.
Given the current uncertainties of the fates of Affordable Care Act, Medicare, and other major systems supporting health care, it is important to know the best approach to take in advocating for academic neurology and your department’s needs. At the course on Oct. 16, come learn about current health policy issues and the political climate and determine how and when to be politically active.
To understand the impact that the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) requirements will have on academic neurology, come to the session on Oct. 17. You’ll learn how population health measures and value-based care can be brought into an academic neurology practice, how to report on quality measures in the Merit-based Incentive Payment System, and how to participate in Advanced Alternative Payment Models.
Professional developments courses that will take place each morning during the annual meeting of the American Neurological Association in San Diego offer special opportunities to learn about the rewards and challenges of different career options for neurologists and researchers in academic neurology from those who have gone down a variety of careers paths themselves. Three courses each morning are geared specifically for students, residents, post-docs, and fellows, as well as for professionals at early-, mid-, and university-chair career levels.
For students, residents, post-docs, and fellows
On Oct. 15, young neurology scholars will begin the course with a discussion on the transition from neurology resident to fellow, and then career pathways as a basic scientist, a clinical scientist/researcher, and clinician-administrator. Last year’s recipients of the Derek Denny-Brown Young Neurological Scholar Award also will provide insights on successful early careers in academic neurology.
Global Health has many opportunities for individuals who are looking at potential career paths in neurology to conduct research, clinical care, or educate others in low- to middle-income countries. Speakers on Oct. 16 will share their experiences and discuss emerging trends in global health in neurology and ways in which individuals might pursue careers or opportunities that complement pursuits in academic neurology.
A workshop on Oct. 17 will focus on the essential skills needed for a successful job-seeking experience in academic neurology. There will be opportunities to practice interviewing and negotiating skills, as well as to learn how to market your research and abilities when the opportunity strikes and time is limited.
For early- to mid-career levels
Finding a niche and a successful career trajectory takes a good deal of planning and taking opportunities when the time is right. On Oct. 15, several mid-career level academic neurologists will share their career trajectories and alternative methods they have used for obtaining support and funding for their clinical research, educational enterprises, and curricular development.
The Oct. 16 career development course will outline methods for setting milestones for career development and finding the resources and mentoring individuals you will need for career advancement.
To learn skills and discover tools that will help to write successful grant proposals, particularly for the National Institutes of Health, come to the session on Oct. 17. You can learn how to develop your grant application, respond to critiques of your application, and hear about a variety of sources of funding.
For university chairs of neurology
At a time in which funding for salaries is hampered by many factors, salary disparities are changing across subspecialties as well as in different faculty positions, with some disparities widening and others shrinking. Come to the career development course on Oct. 15 to learn about novel revenue sources and ways in which you can best subsidize the salaries of faculties in your department as well as offer nonmonetary compensation.
Given the current uncertainties of the fates of Affordable Care Act, Medicare, and other major systems supporting health care, it is important to know the best approach to take in advocating for academic neurology and your department’s needs. At the course on Oct. 16, come learn about current health policy issues and the political climate and determine how and when to be politically active.
To understand the impact that the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) requirements will have on academic neurology, come to the session on Oct. 17. You’ll learn how population health measures and value-based care can be brought into an academic neurology practice, how to report on quality measures in the Merit-based Incentive Payment System, and how to participate in Advanced Alternative Payment Models.