Jeff Evans

Unacceptable pain more often remains among patients with early, methotrexate-refractory (RA who move on to triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine than biologic combination therapy with the tumor necrosis factor inhibitor infliximab (Remicade) plus methotrexate, according to findings from 21 months of follow-up in a post hoc analysis of data from the randomized, controlled Swedish Farmacotherapy (SWEFOT) trial.

Although RA patients who took biologic combination therapy had 32% lower risk for unacceptable pain (rated at >40 mm on a 0- to 100-mm visual analog scale) at 21 months, they still had no difference from patients taking triple therapy in the rate of pain described as refractory, or unacceptable despite inflammation control (C-reactive protein <10 mg/L).

While these results lend “some support to a better effect on long-term pain for the biological treatment, compared with triple therapy ... our findings are also in line with insufficient effects of current treatment strategies to prevent development of inflammation-independent pain components, warranting early alternative treatment approaches in affected patients,” Tor Olofsson, MD, PhD, of Lund (Sweden) University, and colleagues wrote in Arthritis Care & Research.

The pain outcomes analyzed in this post hoc study were all secondary outcomes of the original open-label SWEFOT trial, which during 2002-2005 enrolled 258 RA patients with less than a year of symptoms who did not reach low disease activity (28-joint Disease Activity Score ≤3.2) after 3 months of methotrexate and randomized them to an addition of either infliximab (3 mg/kg rounded up to nearest 100-mg increment) or sulfasalazine 1,000 mg twice daily plus hydroxychloroquine 400 mg once daily.

Overall, 90 of 128 patients in the infliximab group and 74 of 130 in the triple-therapy group continued the protocol until the 21-month follow-up. Patients in the infliximab group had a significantly lower area under the curve for visual analog scale for pain, most of which was accounted for during months 9-21. The percentage of patients in the infliximab group with unacceptable pain also dropped significantly from 57% at randomization to 32% at 21 months, while no difference was seen for triple therapy patients, of whom 45% had unacceptable pain at 21 months.

While patients in the infliximab group had a significantly lower risk of unacceptable pain without inflammatory control at 21 months, neither treatment arm showed a within-group difference in refractory pain from randomization to the 21-month follow-up.

Nearly one-third of patients overall still reported unacceptable pain 21 months after addition of either infliximab or sulfasalazine plus hydroxychloroquine. And at that time point, refractory pain constituted 82% of all unacceptable pain. “Notably, this pattern – with a domination of refractory pain – was evident already 3 months after starting combination therapy,” Dr. Olofsson and colleagues wrote.

The original SWEFOT study was supported in part by a grant from the Swedish Rheumatism Association, and in part by an annual unrestricted grant from Schering-Plough Sweden (now Merck Sharp & Dohme). The post hoc analysis was supported by Lund University and the Kockska Foundation, the Swedish Research Council, and the Stockholm County Council. Two authors disclosed financial relationships with multiple pharmaceutical companies.

jevans@mdedge.com

SOURCE: Olofsson T et al. Arthritis Care Res. 2020 May 20. doi: 10.1002/acr.24264.

Unacceptable pain more often remains among patients with early, methotrexate-refractory (RA who move on to triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine than biologic combination therapy with the tumor necrosis factor inhibitor infliximab (Remicade) plus methotrexate, according to findings from 21 months of follow-up in a post hoc analysis of data from the randomized, controlled Swedish Farmacotherapy (SWEFOT) trial.

Although RA patients who took biologic combination therapy had 32% lower risk for unacceptable pain (rated at >40 mm on a 0- to 100-mm visual analog scale) at 21 months, they still had no difference from patients taking triple therapy in the rate of pain described as refractory, or unacceptable despite inflammation control (C-reactive protein <10 mg/L).

While these results lend “some support to a better effect on long-term pain for the biological treatment, compared with triple therapy ... our findings are also in line with insufficient effects of current treatment strategies to prevent development of inflammation-independent pain components, warranting early alternative treatment approaches in affected patients,” Tor Olofsson, MD, PhD, of Lund (Sweden) University, and colleagues wrote in Arthritis Care & Research.

The pain outcomes analyzed in this post hoc study were all secondary outcomes of the original open-label SWEFOT trial, which during 2002-2005 enrolled 258 RA patients with less than a year of symptoms who did not reach low disease activity (28-joint Disease Activity Score ≤3.2) after 3 months of methotrexate and randomized them to an addition of either infliximab (3 mg/kg rounded up to nearest 100-mg increment) or sulfasalazine 1,000 mg twice daily plus hydroxychloroquine 400 mg once daily.

Overall, 90 of 128 patients in the infliximab group and 74 of 130 in the triple-therapy group continued the protocol until the 21-month follow-up. Patients in the infliximab group had a significantly lower area under the curve for visual analog scale for pain, most of which was accounted for during months 9-21. The percentage of patients in the infliximab group with unacceptable pain also dropped significantly from 57% at randomization to 32% at 21 months, while no difference was seen for triple therapy patients, of whom 45% had unacceptable pain at 21 months.

While patients in the infliximab group had a significantly lower risk of unacceptable pain without inflammatory control at 21 months, neither treatment arm showed a within-group difference in refractory pain from randomization to the 21-month follow-up.

Nearly one-third of patients overall still reported unacceptable pain 21 months after addition of either infliximab or sulfasalazine plus hydroxychloroquine. And at that time point, refractory pain constituted 82% of all unacceptable pain. “Notably, this pattern – with a domination of refractory pain – was evident already 3 months after starting combination therapy,” Dr. Olofsson and colleagues wrote.

The original SWEFOT study was supported in part by a grant from the Swedish Rheumatism Association, and in part by an annual unrestricted grant from Schering-Plough Sweden (now Merck Sharp & Dohme). The post hoc analysis was supported by Lund University and the Kockska Foundation, the Swedish Research Council, and the Stockholm County Council. Two authors disclosed financial relationships with multiple pharmaceutical companies.

jevans@mdedge.com

SOURCE: Olofsson T et al. Arthritis Care Res. 2020 May 20. doi: 10.1002/acr.24264.

Unacceptable pain more often remains among patients with early, methotrexate-refractory (RA who move on to triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine than biologic combination therapy with the tumor necrosis factor inhibitor infliximab (Remicade) plus methotrexate, according to findings from 21 months of follow-up in a post hoc analysis of data from the randomized, controlled Swedish Farmacotherapy (SWEFOT) trial.

Although RA patients who took biologic combination therapy had 32% lower risk for unacceptable pain (rated at >40 mm on a 0- to 100-mm visual analog scale) at 21 months, they still had no difference from patients taking triple therapy in the rate of pain described as refractory, or unacceptable despite inflammation control (C-reactive protein <10 mg/L).

While these results lend “some support to a better effect on long-term pain for the biological treatment, compared with triple therapy ... our findings are also in line with insufficient effects of current treatment strategies to prevent development of inflammation-independent pain components, warranting early alternative treatment approaches in affected patients,” Tor Olofsson, MD, PhD, of Lund (Sweden) University, and colleagues wrote in Arthritis Care & Research.

The pain outcomes analyzed in this post hoc study were all secondary outcomes of the original open-label SWEFOT trial, which during 2002-2005 enrolled 258 RA patients with less than a year of symptoms who did not reach low disease activity (28-joint Disease Activity Score ≤3.2) after 3 months of methotrexate and randomized them to an addition of either infliximab (3 mg/kg rounded up to nearest 100-mg increment) or sulfasalazine 1,000 mg twice daily plus hydroxychloroquine 400 mg once daily.

Overall, 90 of 128 patients in the infliximab group and 74 of 130 in the triple-therapy group continued the protocol until the 21-month follow-up. Patients in the infliximab group had a significantly lower area under the curve for visual analog scale for pain, most of which was accounted for during months 9-21. The percentage of patients in the infliximab group with unacceptable pain also dropped significantly from 57% at randomization to 32% at 21 months, while no difference was seen for triple therapy patients, of whom 45% had unacceptable pain at 21 months.

While patients in the infliximab group had a significantly lower risk of unacceptable pain without inflammatory control at 21 months, neither treatment arm showed a within-group difference in refractory pain from randomization to the 21-month follow-up.

Nearly one-third of patients overall still reported unacceptable pain 21 months after addition of either infliximab or sulfasalazine plus hydroxychloroquine. And at that time point, refractory pain constituted 82% of all unacceptable pain. “Notably, this pattern – with a domination of refractory pain – was evident already 3 months after starting combination therapy,” Dr. Olofsson and colleagues wrote.

The original SWEFOT study was supported in part by a grant from the Swedish Rheumatism Association, and in part by an annual unrestricted grant from Schering-Plough Sweden (now Merck Sharp & Dohme). The post hoc analysis was supported by Lund University and the Kockska Foundation, the Swedish Research Council, and the Stockholm County Council. Two authors disclosed financial relationships with multiple pharmaceutical companies.

jevans@mdedge.com

SOURCE: Olofsson T et al. Arthritis Care Res. 2020 May 20. doi: 10.1002/acr.24264.

The European League Against Rheumatism has canceled its annual congress scheduled for June 3-6, 2020, in Frankfurt, Germany, and will instead hold a virtual meeting around the same time frame, according to a message from the organization’s president, Iain McInnes, MD, PhD.

“As a scientific medical society, it is our duty to ensure that our medical and health professional participants are available at the forefront of patient care. We are also concerned that bringing our RMD [rheumatic and musculoskeletal disease] patient delegates into a large meeting venue would be extremely unwise at this time,” Dr. McInnes wrote.

While the details of the virtual congress experience have yet to be worked out, Dr. McInnes said that its offerings “will be accessible on demand over a timeframe of several months,” and they “will also publish abstracts/posters online and provide registered delegates with the 1-year access to our journal, the Annals of Rheumatic Diseases.”

The EULAR president also asked for patience as the details of the virtual congress are determined. “We ask you to be patient for a little while longer to give us the time to develop clear answers to all your questions. Our volunteers and staff in the EULAR Office are currently working hard to develop the best possible solutions for this new scenario.”

jevans@mdedge.com

The European League Against Rheumatism has canceled its annual congress scheduled for June 3-6, 2020, in Frankfurt, Germany, and will instead hold a virtual meeting around the same time frame, according to a message from the organization’s president, Iain McInnes, MD, PhD.

“As a scientific medical society, it is our duty to ensure that our medical and health professional participants are available at the forefront of patient care. We are also concerned that bringing our RMD [rheumatic and musculoskeletal disease] patient delegates into a large meeting venue would be extremely unwise at this time,” Dr. McInnes wrote.

While the details of the virtual congress experience have yet to be worked out, Dr. McInnes said that its offerings “will be accessible on demand over a timeframe of several months,” and they “will also publish abstracts/posters online and provide registered delegates with the 1-year access to our journal, the Annals of Rheumatic Diseases.”

The EULAR president also asked for patience as the details of the virtual congress are determined. “We ask you to be patient for a little while longer to give us the time to develop clear answers to all your questions. Our volunteers and staff in the EULAR Office are currently working hard to develop the best possible solutions for this new scenario.”

jevans@mdedge.com

The European League Against Rheumatism has canceled its annual congress scheduled for June 3-6, 2020, in Frankfurt, Germany, and will instead hold a virtual meeting around the same time frame, according to a message from the organization’s president, Iain McInnes, MD, PhD.

“As a scientific medical society, it is our duty to ensure that our medical and health professional participants are available at the forefront of patient care. We are also concerned that bringing our RMD [rheumatic and musculoskeletal disease] patient delegates into a large meeting venue would be extremely unwise at this time,” Dr. McInnes wrote.

While the details of the virtual congress experience have yet to be worked out, Dr. McInnes said that its offerings “will be accessible on demand over a timeframe of several months,” and they “will also publish abstracts/posters online and provide registered delegates with the 1-year access to our journal, the Annals of Rheumatic Diseases.”

The EULAR president also asked for patience as the details of the virtual congress are determined. “We ask you to be patient for a little while longer to give us the time to develop clear answers to all your questions. Our volunteers and staff in the EULAR Office are currently working hard to develop the best possible solutions for this new scenario.”

jevans@mdedge.com

Physicians and pharmacists are reporting shortages of hydroxychloroquine and chloroquine following President Trump’s promotion of the medications as potential COVID-19 treatments, leaving patients with rheumatic diseases wondering how it will impact their access.

The American Medical Association, the American Pharmacists Association, and the American Society of Health-System Pharmacists, issued a joint statement that strongly opposed prophylactic prescribing of these medications for COVID-19 or stockpiling them in anticipation of use for COVID-19. The concerns over shortages have also prompted the American College of Rheumatology, American Academy of Dermatology, Arthritis Foundation, and Lupus Foundation of America to send a joint statement to the Trump administration and the nation’s governors highlighting critical hydroxychloroquine access issues and asking policymakers to work together with health care providers and patient communities to ensure continued availability of these drugs.

Now rheumatologists are trying to reassure patients with lupus or other rheumatic diseases who take the antimalarials that they will be available and are relatively easy for manufacturers to produce.

In a Q and A interview, NYU Langone Health rheumatology division director and Lupus Center director Jill P. Buyon, MD, and associate professor of rheumatology, Peter M. Izmirly, MD, noted that, while shortages have been reported across the United States because of large increases in off-label prescribing, many of the drugs’ manufacturers have committed to donating millions of doses and/or stepping up production to meet demand.

Later in this article, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Langone Health, New York, answered questions about a new multicenter study called COLCORONA getting underway to test the anti-inflammatory drug colchicine. The answers in this Q&A have been edited for length and clarity. 
 

Questions about hydroxychloroquine shortage

Q: What is the current situation with hydroxychloroquine in your practice?

A: We have been getting calls from our patients asking about getting refills for hydroxychloroquine. Our group has been calling local pharmacies asking about the availability of hydroxychloroquine, and we are compiling a list of pharmacies in New York with current availabilities to share with patients. We are somewhat limited by our electronic health record system, Epic, which can only send a prescription to one pharmacy, so that has placed some limitations on knowing where it is available. Some pharmacies have not had hydroxychloroquine available, while others have. We have also been encouraging patients to check online and look for mail-order possibilities for 90-day supplies.

Nearly all prescriptions are for generic hydroxychloroquine. Branded hydroxychloroquine (Plaquenil) is much more expensive, and we can run into obstacles with getting it approved by insurers, too.
 

Q: What are you telling patients who seek to refill their prescription or call with concerns? Is it feasible for patients to stop hydroxychloroquine or cut their dosage if necessary?

A: If someone’s been on hydroxychloroquine and has benefited from its use there’s no reason to come off it at this time, and given the possibility that it may have an effect on COVID-19, that is all the better. But we want to reassure patients that they can get the drug and that it is not difficult to manufacture.

Given the significantly higher risk of disease flare that was first described in lupus patients who discontinued hydroxychloroquine in the Canadian Hydroxychloroquine Study Group’s 1991 randomized, controlled trial, it is not advisable for patients to stop the drug.

Some patients do split their dosage day-to-day if they are taking less than 400 mg daily, such that someone taking 300 mg daily may take two 200-mg tablets one day and just one 200-mg tablet the next day, and so on. To avoid eye toxicity that can occur after years of taking the drug, hydroxychloroquine is generally prescribed based on weight at 5 mg/kg.

The drug also stays in the body for quite a while [often up to 3 months and even longer], so that is helpful for patients to know.

Given the current situation and the possibility of its effectiveness against COVID-19, it is ironic that we are actually trying to recruit older lupus patients who have had long-term stable disease while on hydroxychloroquine to a trial of stopping the drug to reduce the risk of developing the side effect of retinopathy. We want to see if patients can safely withdraw hydroxychloroquine without flaring, so we hope to not run into enrollment difficulties based on the current situation with COVID-19.
 

Q: How do you view the balance between having enough hydroxychloroquine for patients with lupus or other rheumatic diseases and its use in COVID-19 patients?

A: We want to reassure patients that hydroxychloroquine will be available, and there is no reason to hoard the drug or to worry excessively about being unable to obtain it. Efforts to increase production by Mylan, Teva, Sanofi, Novartis, and other manufacturers of hydroxychloroquine should really help out.

Q: Are there pharmacy restrictions on prescription amounts?

A: This is not universal at this time, but some institutions are cutting back and offering only 1-month supplies.
 

Colchicine COVID-19 trial underway

Dr. Pillinger, of NYU Langone Health, explored the COLCORONA study of colchicine as a treatment for people infected with COVID-19 and the worry that shortage concerns may arise for it, too. 

Q: What is the general availability of colchicine and its susceptibility to shortage?

A: There are two major manufacturers of colchicine in the United States, Takeda and Hikma, who together manufacture the majority of the drug.

The greatest use of colchicine in the United States is for gout, which affects approximately 4 million Americans, but the drug is not used chronically, so a much smaller number of patients are using colchicine at any one time. Colchicine is also used for other inflammatory conditions, primarily calcium pyrophosphate crystal disease and familial Mediterranean fever (FMF is rare in the United States). Cardiologists also regularly prescribe colchicine in pericarditis for short-term use. Physicians may use it off label for other purposes, too.

Overall, the number of patients using colchicine is much larger than that for the use of hydroxychloroquine, for example, suggesting that the immediate risk of shortage could be lower. However, if individuals started using it off label, or prescribing inappropriately for the COVID-19 indication, the supply would rapidly run short.
 

Q: What other points are there to consider regarding the use of colchicine to treat COVID-19?

A: There is no evidence – zero – that colchicine has any benefit for COVID-19, not even case reports. There is some rationale that it might be beneficial, but that is exactly why the COLCORONA trial would be logical to try.

The COLCORONA trial is exactly the kind of trial that would be needed for assessing colchicine, and it is big enough and happening quickly enough to get an answer. But if people start to use colchicine off label, we may never know the truth.

While colchicine can be used safely in most people, it can be very problematic and requires an experienced doctor’s supervision. Overdoses can be fatal, and colchicine interacts with many drugs, all of which require dose adjustment and some of which must be stopped in order to use colchicine – it isn’t candy. Some of the other drugs being looked at for COVID-19 in fact may interact with colchicine.

Colchicine must also be dose adjusted for kidney disease, and, in some of the COVID-19 patients, kidney function changes rapidly. So again, its use would require expert supervision even if there were evidence for its utility.

The side effects of colchicine, if mis-dosed, can be very unpleasant, including nausea, vomiting, and diarrhea. Even at the apparent right dose, some people will get these side effects, so colchicine has to be something that works to make the risk/benefit ratio worth it.

Some preparations of colchicine are made combined with probenecid, a gout drug. This is even more problematic because probenecid can raise the level of drugs excreted by the kidney and could affect other treatments.

So in sum, what may be a good idea in theory can turn out to be a disastrous idea in practice, and here we have nothing but theory. This is not an agent to use randomly; the studies will be rushed out quickly and hopefully will give us the knowledge to know what to do.

Dr. Izmirly and Dr. Buyon said they have research grants with the National Institutes of Health to study hydroxychloroquine in patients with lupus and in anti–SSA/Ro-positive pregnant women with a previous child with congenital heart block. Dr. Pillinger reports that he has an investigator-initiated grant from Hikma to study colchicine in osteoarthritis.

jevans@mdedge.com

This article was reformatted on 3/30/2020 for clarity. 

Physicians and pharmacists are reporting shortages of hydroxychloroquine and chloroquine following President Trump’s promotion of the medications as potential COVID-19 treatments, leaving patients with rheumatic diseases wondering how it will impact their access.

The American Medical Association, the American Pharmacists Association, and the American Society of Health-System Pharmacists, issued a joint statement that strongly opposed prophylactic prescribing of these medications for COVID-19 or stockpiling them in anticipation of use for COVID-19. The concerns over shortages have also prompted the American College of Rheumatology, American Academy of Dermatology, Arthritis Foundation, and Lupus Foundation of America to send a joint statement to the Trump administration and the nation’s governors highlighting critical hydroxychloroquine access issues and asking policymakers to work together with health care providers and patient communities to ensure continued availability of these drugs.

Now rheumatologists are trying to reassure patients with lupus or other rheumatic diseases who take the antimalarials that they will be available and are relatively easy for manufacturers to produce.

In a Q and A interview, NYU Langone Health rheumatology division director and Lupus Center director Jill P. Buyon, MD, and associate professor of rheumatology, Peter M. Izmirly, MD, noted that, while shortages have been reported across the United States because of large increases in off-label prescribing, many of the drugs’ manufacturers have committed to donating millions of doses and/or stepping up production to meet demand.

Later in this article, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Langone Health, New York, answered questions about a new multicenter study called COLCORONA getting underway to test the anti-inflammatory drug colchicine. The answers in this Q&A have been edited for length and clarity. 
 

Questions about hydroxychloroquine shortage

Q: What is the current situation with hydroxychloroquine in your practice?

A: We have been getting calls from our patients asking about getting refills for hydroxychloroquine. Our group has been calling local pharmacies asking about the availability of hydroxychloroquine, and we are compiling a list of pharmacies in New York with current availabilities to share with patients. We are somewhat limited by our electronic health record system, Epic, which can only send a prescription to one pharmacy, so that has placed some limitations on knowing where it is available. Some pharmacies have not had hydroxychloroquine available, while others have. We have also been encouraging patients to check online and look for mail-order possibilities for 90-day supplies.

Nearly all prescriptions are for generic hydroxychloroquine. Branded hydroxychloroquine (Plaquenil) is much more expensive, and we can run into obstacles with getting it approved by insurers, too.
 

Q: What are you telling patients who seek to refill their prescription or call with concerns? Is it feasible for patients to stop hydroxychloroquine or cut their dosage if necessary?

A: If someone’s been on hydroxychloroquine and has benefited from its use there’s no reason to come off it at this time, and given the possibility that it may have an effect on COVID-19, that is all the better. But we want to reassure patients that they can get the drug and that it is not difficult to manufacture.

Given the significantly higher risk of disease flare that was first described in lupus patients who discontinued hydroxychloroquine in the Canadian Hydroxychloroquine Study Group’s 1991 randomized, controlled trial, it is not advisable for patients to stop the drug.

Some patients do split their dosage day-to-day if they are taking less than 400 mg daily, such that someone taking 300 mg daily may take two 200-mg tablets one day and just one 200-mg tablet the next day, and so on. To avoid eye toxicity that can occur after years of taking the drug, hydroxychloroquine is generally prescribed based on weight at 5 mg/kg.

The drug also stays in the body for quite a while [often up to 3 months and even longer], so that is helpful for patients to know.

Given the current situation and the possibility of its effectiveness against COVID-19, it is ironic that we are actually trying to recruit older lupus patients who have had long-term stable disease while on hydroxychloroquine to a trial of stopping the drug to reduce the risk of developing the side effect of retinopathy. We want to see if patients can safely withdraw hydroxychloroquine without flaring, so we hope to not run into enrollment difficulties based on the current situation with COVID-19.
 

Q: How do you view the balance between having enough hydroxychloroquine for patients with lupus or other rheumatic diseases and its use in COVID-19 patients?

A: We want to reassure patients that hydroxychloroquine will be available, and there is no reason to hoard the drug or to worry excessively about being unable to obtain it. Efforts to increase production by Mylan, Teva, Sanofi, Novartis, and other manufacturers of hydroxychloroquine should really help out.

Q: Are there pharmacy restrictions on prescription amounts?

A: This is not universal at this time, but some institutions are cutting back and offering only 1-month supplies.
 

Colchicine COVID-19 trial underway

Dr. Pillinger, of NYU Langone Health, explored the COLCORONA study of colchicine as a treatment for people infected with COVID-19 and the worry that shortage concerns may arise for it, too. 

Q: What is the general availability of colchicine and its susceptibility to shortage?

A: There are two major manufacturers of colchicine in the United States, Takeda and Hikma, who together manufacture the majority of the drug.

The greatest use of colchicine in the United States is for gout, which affects approximately 4 million Americans, but the drug is not used chronically, so a much smaller number of patients are using colchicine at any one time. Colchicine is also used for other inflammatory conditions, primarily calcium pyrophosphate crystal disease and familial Mediterranean fever (FMF is rare in the United States). Cardiologists also regularly prescribe colchicine in pericarditis for short-term use. Physicians may use it off label for other purposes, too.

Overall, the number of patients using colchicine is much larger than that for the use of hydroxychloroquine, for example, suggesting that the immediate risk of shortage could be lower. However, if individuals started using it off label, or prescribing inappropriately for the COVID-19 indication, the supply would rapidly run short.
 

Q: What other points are there to consider regarding the use of colchicine to treat COVID-19?

A: There is no evidence – zero – that colchicine has any benefit for COVID-19, not even case reports. There is some rationale that it might be beneficial, but that is exactly why the COLCORONA trial would be logical to try.

The COLCORONA trial is exactly the kind of trial that would be needed for assessing colchicine, and it is big enough and happening quickly enough to get an answer. But if people start to use colchicine off label, we may never know the truth.

While colchicine can be used safely in most people, it can be very problematic and requires an experienced doctor’s supervision. Overdoses can be fatal, and colchicine interacts with many drugs, all of which require dose adjustment and some of which must be stopped in order to use colchicine – it isn’t candy. Some of the other drugs being looked at for COVID-19 in fact may interact with colchicine.

Colchicine must also be dose adjusted for kidney disease, and, in some of the COVID-19 patients, kidney function changes rapidly. So again, its use would require expert supervision even if there were evidence for its utility.

The side effects of colchicine, if mis-dosed, can be very unpleasant, including nausea, vomiting, and diarrhea. Even at the apparent right dose, some people will get these side effects, so colchicine has to be something that works to make the risk/benefit ratio worth it.

Some preparations of colchicine are made combined with probenecid, a gout drug. This is even more problematic because probenecid can raise the level of drugs excreted by the kidney and could affect other treatments.

So in sum, what may be a good idea in theory can turn out to be a disastrous idea in practice, and here we have nothing but theory. This is not an agent to use randomly; the studies will be rushed out quickly and hopefully will give us the knowledge to know what to do.

Dr. Izmirly and Dr. Buyon said they have research grants with the National Institutes of Health to study hydroxychloroquine in patients with lupus and in anti–SSA/Ro-positive pregnant women with a previous child with congenital heart block. Dr. Pillinger reports that he has an investigator-initiated grant from Hikma to study colchicine in osteoarthritis.

jevans@mdedge.com

This article was reformatted on 3/30/2020 for clarity. 

Physicians and pharmacists are reporting shortages of hydroxychloroquine and chloroquine following President Trump’s promotion of the medications as potential COVID-19 treatments, leaving patients with rheumatic diseases wondering how it will impact their access.

The American Medical Association, the American Pharmacists Association, and the American Society of Health-System Pharmacists, issued a joint statement that strongly opposed prophylactic prescribing of these medications for COVID-19 or stockpiling them in anticipation of use for COVID-19. The concerns over shortages have also prompted the American College of Rheumatology, American Academy of Dermatology, Arthritis Foundation, and Lupus Foundation of America to send a joint statement to the Trump administration and the nation’s governors highlighting critical hydroxychloroquine access issues and asking policymakers to work together with health care providers and patient communities to ensure continued availability of these drugs.

Now rheumatologists are trying to reassure patients with lupus or other rheumatic diseases who take the antimalarials that they will be available and are relatively easy for manufacturers to produce.

In a Q and A interview, NYU Langone Health rheumatology division director and Lupus Center director Jill P. Buyon, MD, and associate professor of rheumatology, Peter M. Izmirly, MD, noted that, while shortages have been reported across the United States because of large increases in off-label prescribing, many of the drugs’ manufacturers have committed to donating millions of doses and/or stepping up production to meet demand.

Later in this article, Michael H. Pillinger, MD, a rheumatologist and professor of medicine, biochemistry, and molecular pharmacology at NYU Langone Health, New York, answered questions about a new multicenter study called COLCORONA getting underway to test the anti-inflammatory drug colchicine. The answers in this Q&A have been edited for length and clarity. 
 

Questions about hydroxychloroquine shortage

Q: What is the current situation with hydroxychloroquine in your practice?

A: We have been getting calls from our patients asking about getting refills for hydroxychloroquine. Our group has been calling local pharmacies asking about the availability of hydroxychloroquine, and we are compiling a list of pharmacies in New York with current availabilities to share with patients. We are somewhat limited by our electronic health record system, Epic, which can only send a prescription to one pharmacy, so that has placed some limitations on knowing where it is available. Some pharmacies have not had hydroxychloroquine available, while others have. We have also been encouraging patients to check online and look for mail-order possibilities for 90-day supplies.

Nearly all prescriptions are for generic hydroxychloroquine. Branded hydroxychloroquine (Plaquenil) is much more expensive, and we can run into obstacles with getting it approved by insurers, too.
 

Q: What are you telling patients who seek to refill their prescription or call with concerns? Is it feasible for patients to stop hydroxychloroquine or cut their dosage if necessary?

A: If someone’s been on hydroxychloroquine and has benefited from its use there’s no reason to come off it at this time, and given the possibility that it may have an effect on COVID-19, that is all the better. But we want to reassure patients that they can get the drug and that it is not difficult to manufacture.

Given the significantly higher risk of disease flare that was first described in lupus patients who discontinued hydroxychloroquine in the Canadian Hydroxychloroquine Study Group’s 1991 randomized, controlled trial, it is not advisable for patients to stop the drug.

Some patients do split their dosage day-to-day if they are taking less than 400 mg daily, such that someone taking 300 mg daily may take two 200-mg tablets one day and just one 200-mg tablet the next day, and so on. To avoid eye toxicity that can occur after years of taking the drug, hydroxychloroquine is generally prescribed based on weight at 5 mg/kg.

The drug also stays in the body for quite a while [often up to 3 months and even longer], so that is helpful for patients to know.

Given the current situation and the possibility of its effectiveness against COVID-19, it is ironic that we are actually trying to recruit older lupus patients who have had long-term stable disease while on hydroxychloroquine to a trial of stopping the drug to reduce the risk of developing the side effect of retinopathy. We want to see if patients can safely withdraw hydroxychloroquine without flaring, so we hope to not run into enrollment difficulties based on the current situation with COVID-19.
 

Q: How do you view the balance between having enough hydroxychloroquine for patients with lupus or other rheumatic diseases and its use in COVID-19 patients?

A: We want to reassure patients that hydroxychloroquine will be available, and there is no reason to hoard the drug or to worry excessively about being unable to obtain it. Efforts to increase production by Mylan, Teva, Sanofi, Novartis, and other manufacturers of hydroxychloroquine should really help out.

Q: Are there pharmacy restrictions on prescription amounts?

A: This is not universal at this time, but some institutions are cutting back and offering only 1-month supplies.
 

Colchicine COVID-19 trial underway

Dr. Pillinger, of NYU Langone Health, explored the COLCORONA study of colchicine as a treatment for people infected with COVID-19 and the worry that shortage concerns may arise for it, too. 

Q: What is the general availability of colchicine and its susceptibility to shortage?

A: There are two major manufacturers of colchicine in the United States, Takeda and Hikma, who together manufacture the majority of the drug.

The greatest use of colchicine in the United States is for gout, which affects approximately 4 million Americans, but the drug is not used chronically, so a much smaller number of patients are using colchicine at any one time. Colchicine is also used for other inflammatory conditions, primarily calcium pyrophosphate crystal disease and familial Mediterranean fever (FMF is rare in the United States). Cardiologists also regularly prescribe colchicine in pericarditis for short-term use. Physicians may use it off label for other purposes, too.

Overall, the number of patients using colchicine is much larger than that for the use of hydroxychloroquine, for example, suggesting that the immediate risk of shortage could be lower. However, if individuals started using it off label, or prescribing inappropriately for the COVID-19 indication, the supply would rapidly run short.
 

Q: What other points are there to consider regarding the use of colchicine to treat COVID-19?

A: There is no evidence – zero – that colchicine has any benefit for COVID-19, not even case reports. There is some rationale that it might be beneficial, but that is exactly why the COLCORONA trial would be logical to try.

The COLCORONA trial is exactly the kind of trial that would be needed for assessing colchicine, and it is big enough and happening quickly enough to get an answer. But if people start to use colchicine off label, we may never know the truth.

While colchicine can be used safely in most people, it can be very problematic and requires an experienced doctor’s supervision. Overdoses can be fatal, and colchicine interacts with many drugs, all of which require dose adjustment and some of which must be stopped in order to use colchicine – it isn’t candy. Some of the other drugs being looked at for COVID-19 in fact may interact with colchicine.

Colchicine must also be dose adjusted for kidney disease, and, in some of the COVID-19 patients, kidney function changes rapidly. So again, its use would require expert supervision even if there were evidence for its utility.

The side effects of colchicine, if mis-dosed, can be very unpleasant, including nausea, vomiting, and diarrhea. Even at the apparent right dose, some people will get these side effects, so colchicine has to be something that works to make the risk/benefit ratio worth it.

Some preparations of colchicine are made combined with probenecid, a gout drug. This is even more problematic because probenecid can raise the level of drugs excreted by the kidney and could affect other treatments.

So in sum, what may be a good idea in theory can turn out to be a disastrous idea in practice, and here we have nothing but theory. This is not an agent to use randomly; the studies will be rushed out quickly and hopefully will give us the knowledge to know what to do.

Dr. Izmirly and Dr. Buyon said they have research grants with the National Institutes of Health to study hydroxychloroquine in patients with lupus and in anti–SSA/Ro-positive pregnant women with a previous child with congenital heart block. Dr. Pillinger reports that he has an investigator-initiated grant from Hikma to study colchicine in osteoarthritis.

jevans@mdedge.com

This article was reformatted on 3/30/2020 for clarity. 

The American College of Rheumatology decided to cancel its upcoming Division & Program Directors Conference and State-of-the-Art Clinical Symposium because of “the escalation in the number of people affected [by the COVID-19 situation], and the likelihood of potentially increasing the exposure to COVID-19.”

The Division & Program Directors Conference was slated to take place March 13-14 in Chicago, while the State-of-the-Art Clinical Symposium was scheduled to happen March 27-29 in New Orleans. In both cases, the organizers are exploring alternative ways to deliver or present the content.

The ACR has not made a decision on the status of its Pediatric Rheumatology Symposium, April 29-May 2, New Orleans, but plans to do so by March 30.

jevans@mdedge.com

The American College of Rheumatology decided to cancel its upcoming Division & Program Directors Conference and State-of-the-Art Clinical Symposium because of “the escalation in the number of people affected [by the COVID-19 situation], and the likelihood of potentially increasing the exposure to COVID-19.”

The Division & Program Directors Conference was slated to take place March 13-14 in Chicago, while the State-of-the-Art Clinical Symposium was scheduled to happen March 27-29 in New Orleans. In both cases, the organizers are exploring alternative ways to deliver or present the content.

The ACR has not made a decision on the status of its Pediatric Rheumatology Symposium, April 29-May 2, New Orleans, but plans to do so by March 30.

jevans@mdedge.com

The American College of Rheumatology decided to cancel its upcoming Division & Program Directors Conference and State-of-the-Art Clinical Symposium because of “the escalation in the number of people affected [by the COVID-19 situation], and the likelihood of potentially increasing the exposure to COVID-19.”

The Division & Program Directors Conference was slated to take place March 13-14 in Chicago, while the State-of-the-Art Clinical Symposium was scheduled to happen March 27-29 in New Orleans. In both cases, the organizers are exploring alternative ways to deliver or present the content.

The ACR has not made a decision on the status of its Pediatric Rheumatology Symposium, April 29-May 2, New Orleans, but plans to do so by March 30.

jevans@mdedge.com

Mobile health technologies currently available for patients with systemic lupus erythematosus (SLE), particularly mobile health (mHealth) apps, are poor quality and have limited “The use of mobile technologies to support health (mHealth technologies), specifically mHealth applications (apps), has the potential to improve outcomes in SLE by empowering patients through education, symptom tracking, and peer support,” first author Lucas Ogura Dantas, of Tufts Medical Center, Boston, and coauthors wrote in Lupus. “These may be particularly powerful tools in SLE which commonly affects young adults, who are typically avid smartphone users familiar with the use of mobile apps.”

jevans@mdedge.com

SOURCE: Dantas LO et al. Lupus. 2020;29:144-56.

Mobile health technologies currently available for patients with systemic lupus erythematosus (SLE), particularly mobile health (mHealth) apps, are poor quality and have limited “The use of mobile technologies to support health (mHealth technologies), specifically mHealth applications (apps), has the potential to improve outcomes in SLE by empowering patients through education, symptom tracking, and peer support,” first author Lucas Ogura Dantas, of Tufts Medical Center, Boston, and coauthors wrote in Lupus. “These may be particularly powerful tools in SLE which commonly affects young adults, who are typically avid smartphone users familiar with the use of mobile apps.”

jevans@mdedge.com

SOURCE: Dantas LO et al. Lupus. 2020;29:144-56.

Mobile health technologies currently available for patients with systemic lupus erythematosus (SLE), particularly mobile health (mHealth) apps, are poor quality and have limited “The use of mobile technologies to support health (mHealth technologies), specifically mHealth applications (apps), has the potential to improve outcomes in SLE by empowering patients through education, symptom tracking, and peer support,” first author Lucas Ogura Dantas, of Tufts Medical Center, Boston, and coauthors wrote in Lupus. “These may be particularly powerful tools in SLE which commonly affects young adults, who are typically avid smartphone users familiar with the use of mobile apps.”

jevans@mdedge.com

SOURCE: Dantas LO et al. Lupus. 2020;29:144-56.

The British Society for Rheumatology (BSR) has canceled its annual conference that was scheduled to take place April 20-22 in Glasgow.

“After careful monitoring of the COVID-19 (coronavirus) situation ... [and] in light of increasing demands on health services, our Board of Trustees felt it was no longer appropriate to host a large-scale event nor to take medical professionals away from where they may be needed most in the coming weeks,” the organization announced on its website.

The BSR said that it will soon have more information available for people affected, including “details of how we will showcase some of the content that would have been celebrated at the event.”

jevans@mdedge.com

The British Society for Rheumatology (BSR) has canceled its annual conference that was scheduled to take place April 20-22 in Glasgow.

“After careful monitoring of the COVID-19 (coronavirus) situation ... [and] in light of increasing demands on health services, our Board of Trustees felt it was no longer appropriate to host a large-scale event nor to take medical professionals away from where they may be needed most in the coming weeks,” the organization announced on its website.

The BSR said that it will soon have more information available for people affected, including “details of how we will showcase some of the content that would have been celebrated at the event.”

jevans@mdedge.com

The British Society for Rheumatology (BSR) has canceled its annual conference that was scheduled to take place April 20-22 in Glasgow.

“After careful monitoring of the COVID-19 (coronavirus) situation ... [and] in light of increasing demands on health services, our Board of Trustees felt it was no longer appropriate to host a large-scale event nor to take medical professionals away from where they may be needed most in the coming weeks,” the organization announced on its website.

The BSR said that it will soon have more information available for people affected, including “details of how we will showcase some of the content that would have been celebrated at the event.”

jevans@mdedge.com

Women with systemic lupus erythematosus (SLE) who experience hypertensive disorders of pregnancy may have a higher rate of cardiovascular outcomes after pregnancy, as well as a higher rate of hypertension later in life, than do those without maternal hypertension, according to findings from a Swedish population-based, longitudinal cohort study.

“Premature CVD [cardiovascular disease] is a well-documented complication in women with SLE, which is likely, at least in part, due to renal disease, prothrombotic [antiphospholipid antibodies], and systemic inflammation. Our data confirm that women who experience a hypertensive disorder in pregnancy [HDP] are at greater risk of developing hypertension after pregnancy, and that this association is also evident for women with SLE. Women with SLE and HDP were also at increased risk of CVD, particularly stroke, at young ages and should be monitored closely and consider treatment to attenuate risk,” wrote first author Julia F. Simard, ScD, of Stanford (Calif.) University and colleagues in Arthritis Care & Research.

To reach those conclusions, the researchers identified 3,340 women in the Swedish Medical Birth Register with their first singleton delivery during 1987-2012. They matched each of the 450 women with prevalent SLE from the Medical Birth Register to 5 women without SLE in the National Patient Register based on sex, birth year, calendar time, and county of residence.

During a median follow-up period of nearly 11 years, women with SLE had an unadjusted incidence rate of incident cardiovascular outcomes of 50 cases per 10,000 person-years versus 7.2 for women without SLE. Cardiovascular outcomes included fatal and nonfatal acute MI, fatal and nonfatal stroke, transient ischemic attacks, unstable angina, and heart failure. A history of HDP in women with SLE, including preeclampsia, was linked with about a twofold higher rate of cardiovascular outcomes regardless of multiple sensitivity analyses, both before and after adjusting for maternal age at delivery, county of birth, education, body mass index, and first-trimester smoking.

The researchers found that the hazard ratio for cardiovascular outcomes in women with SLE and HDP was about eight times higher than the hazard ratio for women without SLE but with HDP, but the relative rarity of cardiovascular events seen during the follow-up period, particularly among women without SLE, made it so that they “could not confirm established associations between HDP and CVD, possibly due to the relatively short follow-up time given that premenopausal CVD is rare among women free of SLE.”

HDP was associated with a threefold higher risk for incident hypertension later in life regardless of SLE status, even though the unadjusted incidence rate was 524 cases per 10,000 person-years among women with both SLE and HDP, compared with 177 per 10,000 person-years among women with HDP in the general population, which sensitivity analyses suggested “was not due to misclassification of antihypertensive use for renal disease in women with SLE nor antihypertensive use for possible HDP in subsequent pregnancies,” the researchers wrote.

Several authors reported research grants from the National Institutes of Health, the Karolinska Institute, the Swedish Research Council, Swedish Heart-Lung Foundation, Stockholm County Council, the King Gustaf V 80th Birthday Fund, the Swedish Rheumatism Association, and Ingegerd Johansson’s Foundation that helped to fund the study. All authors reported having no competing interests.

jevans@mdedge.com

SOURCE: Simard JF et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24160.

Women with systemic lupus erythematosus (SLE) who experience hypertensive disorders of pregnancy may have a higher rate of cardiovascular outcomes after pregnancy, as well as a higher rate of hypertension later in life, than do those without maternal hypertension, according to findings from a Swedish population-based, longitudinal cohort study.

“Premature CVD [cardiovascular disease] is a well-documented complication in women with SLE, which is likely, at least in part, due to renal disease, prothrombotic [antiphospholipid antibodies], and systemic inflammation. Our data confirm that women who experience a hypertensive disorder in pregnancy [HDP] are at greater risk of developing hypertension after pregnancy, and that this association is also evident for women with SLE. Women with SLE and HDP were also at increased risk of CVD, particularly stroke, at young ages and should be monitored closely and consider treatment to attenuate risk,” wrote first author Julia F. Simard, ScD, of Stanford (Calif.) University and colleagues in Arthritis Care & Research.

To reach those conclusions, the researchers identified 3,340 women in the Swedish Medical Birth Register with their first singleton delivery during 1987-2012. They matched each of the 450 women with prevalent SLE from the Medical Birth Register to 5 women without SLE in the National Patient Register based on sex, birth year, calendar time, and county of residence.

During a median follow-up period of nearly 11 years, women with SLE had an unadjusted incidence rate of incident cardiovascular outcomes of 50 cases per 10,000 person-years versus 7.2 for women without SLE. Cardiovascular outcomes included fatal and nonfatal acute MI, fatal and nonfatal stroke, transient ischemic attacks, unstable angina, and heart failure. A history of HDP in women with SLE, including preeclampsia, was linked with about a twofold higher rate of cardiovascular outcomes regardless of multiple sensitivity analyses, both before and after adjusting for maternal age at delivery, county of birth, education, body mass index, and first-trimester smoking.

The researchers found that the hazard ratio for cardiovascular outcomes in women with SLE and HDP was about eight times higher than the hazard ratio for women without SLE but with HDP, but the relative rarity of cardiovascular events seen during the follow-up period, particularly among women without SLE, made it so that they “could not confirm established associations between HDP and CVD, possibly due to the relatively short follow-up time given that premenopausal CVD is rare among women free of SLE.”

HDP was associated with a threefold higher risk for incident hypertension later in life regardless of SLE status, even though the unadjusted incidence rate was 524 cases per 10,000 person-years among women with both SLE and HDP, compared with 177 per 10,000 person-years among women with HDP in the general population, which sensitivity analyses suggested “was not due to misclassification of antihypertensive use for renal disease in women with SLE nor antihypertensive use for possible HDP in subsequent pregnancies,” the researchers wrote.

Several authors reported research grants from the National Institutes of Health, the Karolinska Institute, the Swedish Research Council, Swedish Heart-Lung Foundation, Stockholm County Council, the King Gustaf V 80th Birthday Fund, the Swedish Rheumatism Association, and Ingegerd Johansson’s Foundation that helped to fund the study. All authors reported having no competing interests.

jevans@mdedge.com

SOURCE: Simard JF et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24160.

Women with systemic lupus erythematosus (SLE) who experience hypertensive disorders of pregnancy may have a higher rate of cardiovascular outcomes after pregnancy, as well as a higher rate of hypertension later in life, than do those without maternal hypertension, according to findings from a Swedish population-based, longitudinal cohort study.

“Premature CVD [cardiovascular disease] is a well-documented complication in women with SLE, which is likely, at least in part, due to renal disease, prothrombotic [antiphospholipid antibodies], and systemic inflammation. Our data confirm that women who experience a hypertensive disorder in pregnancy [HDP] are at greater risk of developing hypertension after pregnancy, and that this association is also evident for women with SLE. Women with SLE and HDP were also at increased risk of CVD, particularly stroke, at young ages and should be monitored closely and consider treatment to attenuate risk,” wrote first author Julia F. Simard, ScD, of Stanford (Calif.) University and colleagues in Arthritis Care & Research.

To reach those conclusions, the researchers identified 3,340 women in the Swedish Medical Birth Register with their first singleton delivery during 1987-2012. They matched each of the 450 women with prevalent SLE from the Medical Birth Register to 5 women without SLE in the National Patient Register based on sex, birth year, calendar time, and county of residence.

During a median follow-up period of nearly 11 years, women with SLE had an unadjusted incidence rate of incident cardiovascular outcomes of 50 cases per 10,000 person-years versus 7.2 for women without SLE. Cardiovascular outcomes included fatal and nonfatal acute MI, fatal and nonfatal stroke, transient ischemic attacks, unstable angina, and heart failure. A history of HDP in women with SLE, including preeclampsia, was linked with about a twofold higher rate of cardiovascular outcomes regardless of multiple sensitivity analyses, both before and after adjusting for maternal age at delivery, county of birth, education, body mass index, and first-trimester smoking.

The researchers found that the hazard ratio for cardiovascular outcomes in women with SLE and HDP was about eight times higher than the hazard ratio for women without SLE but with HDP, but the relative rarity of cardiovascular events seen during the follow-up period, particularly among women without SLE, made it so that they “could not confirm established associations between HDP and CVD, possibly due to the relatively short follow-up time given that premenopausal CVD is rare among women free of SLE.”

HDP was associated with a threefold higher risk for incident hypertension later in life regardless of SLE status, even though the unadjusted incidence rate was 524 cases per 10,000 person-years among women with both SLE and HDP, compared with 177 per 10,000 person-years among women with HDP in the general population, which sensitivity analyses suggested “was not due to misclassification of antihypertensive use for renal disease in women with SLE nor antihypertensive use for possible HDP in subsequent pregnancies,” the researchers wrote.

Several authors reported research grants from the National Institutes of Health, the Karolinska Institute, the Swedish Research Council, Swedish Heart-Lung Foundation, Stockholm County Council, the King Gustaf V 80th Birthday Fund, the Swedish Rheumatism Association, and Ingegerd Johansson’s Foundation that helped to fund the study. All authors reported having no competing interests.

jevans@mdedge.com

SOURCE: Simard JF et al. Arthritis Care Res. 2020 Jan 31. doi: 10.1002/acr.24160.

Tumor necrosis factor inhibitors may slow radiographic progression in the spine of patients with ankylosing spondylitis after at least 4 years of use, according to an analysis of studies with low risk of bias, but no evidence exists for slowed disease progression at the sacroiliac joint, according to a systematic review and meta-analysis of 24 studies.

The review, conducted by Paras Karmacharya, MBBS, and colleagues at the Mayo Clinic in Rochester, Minn., did not find a significant protective effect overall for tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression of ankylosing spondylitis at the spine at 2 and 4 years. But when the researchers restricted the analysis to six studies of TNFi with low risk of bias, the results were significant for slowing radiographic progression at 4 years or more (modified Stoke Ankylosing Spondylitis Spine Score [mSASSS] difference, –2.17).

NSAIDs did not show any benefit in slowing progression at either the spine or sacroiliac joint over a shorter 2-year time span for which results were available. The single study of secukinumab (Cosentyx) that was included in the analysis did not show a significant difference in radiographic progression over 2 years (mean mSASSS difference, –0.34).

For the few studies that included data on radiographic progression in patients with nonradiographic axial spondyloarthritis, there was no effect seen on the spine with either high or low NSAID use at 2 years and no evidence for an effect of TNFi on progression at the sacroiliac joint.

“Although our study showed a significant effect of TNFi on long-term radiographic progression (in sensitivity analysis), none of the included studies provide prospective, long-term, controlled comparison. Most included studies were judged to have a low risk of bias; however predominance of observational and open-label extensions of randomized, controlled trials limits overall level of evidence,” the authors wrote in Arthritis & Rheumatology.

Any benefits of early treatment on slowing the natural progression of disease might support introducing the treatment early with a treat-to-target strategy, similar to RA, the researchers noted. However, “the current guidelines recommend against this due to lack of evidence.”

The analysis involved 18 studies with TNFi, 8 with NSAIDs, and 1 with secukinumab (3 studies contained data for both NSAIDs and TNFi). The investigators used a change of 2 mSASSS units in 2 years or one new syndesmophyte formation in 2 years as the primary endpoint for radiographic progression.

“Further studies should explore the effect of NSAIDs and biologics alone and in combination in patients with early axial spondyloarthritis; their use in the group with high risk of progression should be evaluated with a follow-up [longer than] 4 years to see if effects are more pronounced over time. Newer measures with higher sensitivity to detect structural changes, such as those based on quantitative low-dose CT should be compared to mSASSS for use in clinical trials,” the researchers concluded.

The work was funded by various grants from the National Institutes of Health. The authors reported no relevant disclosures.

jevans@mdedge.com

SOURCE: Karmacharya P et al. Arthritis Rheumatol. 2020 Jan 20. doi: 10.1002/art.41206.

Tumor necrosis factor inhibitors may slow radiographic progression in the spine of patients with ankylosing spondylitis after at least 4 years of use, according to an analysis of studies with low risk of bias, but no evidence exists for slowed disease progression at the sacroiliac joint, according to a systematic review and meta-analysis of 24 studies.

The review, conducted by Paras Karmacharya, MBBS, and colleagues at the Mayo Clinic in Rochester, Minn., did not find a significant protective effect overall for tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression of ankylosing spondylitis at the spine at 2 and 4 years. But when the researchers restricted the analysis to six studies of TNFi with low risk of bias, the results were significant for slowing radiographic progression at 4 years or more (modified Stoke Ankylosing Spondylitis Spine Score [mSASSS] difference, –2.17).

NSAIDs did not show any benefit in slowing progression at either the spine or sacroiliac joint over a shorter 2-year time span for which results were available. The single study of secukinumab (Cosentyx) that was included in the analysis did not show a significant difference in radiographic progression over 2 years (mean mSASSS difference, –0.34).

For the few studies that included data on radiographic progression in patients with nonradiographic axial spondyloarthritis, there was no effect seen on the spine with either high or low NSAID use at 2 years and no evidence for an effect of TNFi on progression at the sacroiliac joint.

“Although our study showed a significant effect of TNFi on long-term radiographic progression (in sensitivity analysis), none of the included studies provide prospective, long-term, controlled comparison. Most included studies were judged to have a low risk of bias; however predominance of observational and open-label extensions of randomized, controlled trials limits overall level of evidence,” the authors wrote in Arthritis & Rheumatology.

Any benefits of early treatment on slowing the natural progression of disease might support introducing the treatment early with a treat-to-target strategy, similar to RA, the researchers noted. However, “the current guidelines recommend against this due to lack of evidence.”

The analysis involved 18 studies with TNFi, 8 with NSAIDs, and 1 with secukinumab (3 studies contained data for both NSAIDs and TNFi). The investigators used a change of 2 mSASSS units in 2 years or one new syndesmophyte formation in 2 years as the primary endpoint for radiographic progression.

“Further studies should explore the effect of NSAIDs and biologics alone and in combination in patients with early axial spondyloarthritis; their use in the group with high risk of progression should be evaluated with a follow-up [longer than] 4 years to see if effects are more pronounced over time. Newer measures with higher sensitivity to detect structural changes, such as those based on quantitative low-dose CT should be compared to mSASSS for use in clinical trials,” the researchers concluded.

The work was funded by various grants from the National Institutes of Health. The authors reported no relevant disclosures.

jevans@mdedge.com

SOURCE: Karmacharya P et al. Arthritis Rheumatol. 2020 Jan 20. doi: 10.1002/art.41206.

Tumor necrosis factor inhibitors may slow radiographic progression in the spine of patients with ankylosing spondylitis after at least 4 years of use, according to an analysis of studies with low risk of bias, but no evidence exists for slowed disease progression at the sacroiliac joint, according to a systematic review and meta-analysis of 24 studies.

The review, conducted by Paras Karmacharya, MBBS, and colleagues at the Mayo Clinic in Rochester, Minn., did not find a significant protective effect overall for tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression of ankylosing spondylitis at the spine at 2 and 4 years. But when the researchers restricted the analysis to six studies of TNFi with low risk of bias, the results were significant for slowing radiographic progression at 4 years or more (modified Stoke Ankylosing Spondylitis Spine Score [mSASSS] difference, –2.17).

NSAIDs did not show any benefit in slowing progression at either the spine or sacroiliac joint over a shorter 2-year time span for which results were available. The single study of secukinumab (Cosentyx) that was included in the analysis did not show a significant difference in radiographic progression over 2 years (mean mSASSS difference, –0.34).

For the few studies that included data on radiographic progression in patients with nonradiographic axial spondyloarthritis, there was no effect seen on the spine with either high or low NSAID use at 2 years and no evidence for an effect of TNFi on progression at the sacroiliac joint.

“Although our study showed a significant effect of TNFi on long-term radiographic progression (in sensitivity analysis), none of the included studies provide prospective, long-term, controlled comparison. Most included studies were judged to have a low risk of bias; however predominance of observational and open-label extensions of randomized, controlled trials limits overall level of evidence,” the authors wrote in Arthritis & Rheumatology.

Any benefits of early treatment on slowing the natural progression of disease might support introducing the treatment early with a treat-to-target strategy, similar to RA, the researchers noted. However, “the current guidelines recommend against this due to lack of evidence.”

The analysis involved 18 studies with TNFi, 8 with NSAIDs, and 1 with secukinumab (3 studies contained data for both NSAIDs and TNFi). The investigators used a change of 2 mSASSS units in 2 years or one new syndesmophyte formation in 2 years as the primary endpoint for radiographic progression.

“Further studies should explore the effect of NSAIDs and biologics alone and in combination in patients with early axial spondyloarthritis; their use in the group with high risk of progression should be evaluated with a follow-up [longer than] 4 years to see if effects are more pronounced over time. Newer measures with higher sensitivity to detect structural changes, such as those based on quantitative low-dose CT should be compared to mSASSS for use in clinical trials,” the researchers concluded.

The work was funded by various grants from the National Institutes of Health. The authors reported no relevant disclosures.

jevans@mdedge.com

SOURCE: Karmacharya P et al. Arthritis Rheumatol. 2020 Jan 20. doi: 10.1002/art.41206.

About one-third of patients with clinically suspect arthralgia who do not develop RA have resolution of symptoms and subclinical joint inflammation on MRI by the end of 2 years, according to investigators from Leiden (the Netherlands) University.

“Thus far, most longitudinal studies performed in patients considered at risk for RA focused on the progression from arthralgia to RA, since (early) identification of individuals that will develop RA is a key point from a clinician’s perspective. However, there is also a group of patients that were considered at risk for RA but over time do not develop RA, meaning that, in hindsight, they possibly have not been truly ‘pre-RA’. This subgroup of patients is unexplored, and the course and outcome of joint symptoms and subclinical inflammation in these patients are yet unknown,” Robin M. ten Brinck and colleagues at Leiden wrote in Arthritis Research & Therapy.

The researchers followed 152 patients with clinically suspicious arthralgia (CSA) who did not develop RA during 2 years of follow-up. All patients had complete clinical data, and 98 had complete 2-year MRI data. Most of the 152 patients were women (74%), and they had a mean age of 47 years, a median of 5 tender joints (out of 68 evaluated), and 19% carried RA-related autoantibodies (rheumatoid factor and/or anti–citrullinated peptide antibody). None of the patients received disease-modifying antirheumatic drugs or glucocorticoids during the study; only NSAIDs were allowed.

Overall, 57 (38%) of the 152 reported resolution of symptoms by 2 years, including 32 (33%) of the 98 patients with serial MRI results available at 2 years. Of the remaining 95 patients who continued to have symptoms, 43 were diagnosed as having persistent CSA, 10 had osteoarthritis, and 13 had tendinomuscular complaints.

There was no statistically significant difference in mean baseline total MRI inflammation scores between those with and without symptom resolution, but among patients with a mean total MRI inflammation score greater than 0 at baseline, those who achieved resolution of symptoms over time had a mean score higher than that of symptom-free patients at baseline. Those patients with resolved symptoms also had a statistically significant decrease in MRI inflammation score at the 2-year follow-up. A smaller and not statistically significant decline in total MRI score was seen in patients without symptom resolution.

“Our study is the first to quantify the percentage of patients presenting with CSA that will have a resolution of symptoms over time. It consists of one-third of all nonprogressing patients and 27% of all patients that were identified as having CSA by rheumatologists,” the researchers wrote.

The study was sponsored by the European Research Council. The authors had no relevant disclosures.

jevans@mdedge.com

SOURCE: ten Brinck RM et al. Arthritis Res Ther. 2020 Jan 16. doi: 10.1186/s13075-020-2102-9.

About one-third of patients with clinically suspect arthralgia who do not develop RA have resolution of symptoms and subclinical joint inflammation on MRI by the end of 2 years, according to investigators from Leiden (the Netherlands) University.

“Thus far, most longitudinal studies performed in patients considered at risk for RA focused on the progression from arthralgia to RA, since (early) identification of individuals that will develop RA is a key point from a clinician’s perspective. However, there is also a group of patients that were considered at risk for RA but over time do not develop RA, meaning that, in hindsight, they possibly have not been truly ‘pre-RA’. This subgroup of patients is unexplored, and the course and outcome of joint symptoms and subclinical inflammation in these patients are yet unknown,” Robin M. ten Brinck and colleagues at Leiden wrote in Arthritis Research & Therapy.

The researchers followed 152 patients with clinically suspicious arthralgia (CSA) who did not develop RA during 2 years of follow-up. All patients had complete clinical data, and 98 had complete 2-year MRI data. Most of the 152 patients were women (74%), and they had a mean age of 47 years, a median of 5 tender joints (out of 68 evaluated), and 19% carried RA-related autoantibodies (rheumatoid factor and/or anti–citrullinated peptide antibody). None of the patients received disease-modifying antirheumatic drugs or glucocorticoids during the study; only NSAIDs were allowed.

Overall, 57 (38%) of the 152 reported resolution of symptoms by 2 years, including 32 (33%) of the 98 patients with serial MRI results available at 2 years. Of the remaining 95 patients who continued to have symptoms, 43 were diagnosed as having persistent CSA, 10 had osteoarthritis, and 13 had tendinomuscular complaints.

There was no statistically significant difference in mean baseline total MRI inflammation scores between those with and without symptom resolution, but among patients with a mean total MRI inflammation score greater than 0 at baseline, those who achieved resolution of symptoms over time had a mean score higher than that of symptom-free patients at baseline. Those patients with resolved symptoms also had a statistically significant decrease in MRI inflammation score at the 2-year follow-up. A smaller and not statistically significant decline in total MRI score was seen in patients without symptom resolution.

“Our study is the first to quantify the percentage of patients presenting with CSA that will have a resolution of symptoms over time. It consists of one-third of all nonprogressing patients and 27% of all patients that were identified as having CSA by rheumatologists,” the researchers wrote.

The study was sponsored by the European Research Council. The authors had no relevant disclosures.

jevans@mdedge.com

SOURCE: ten Brinck RM et al. Arthritis Res Ther. 2020 Jan 16. doi: 10.1186/s13075-020-2102-9.

About one-third of patients with clinically suspect arthralgia who do not develop RA have resolution of symptoms and subclinical joint inflammation on MRI by the end of 2 years, according to investigators from Leiden (the Netherlands) University.

“Thus far, most longitudinal studies performed in patients considered at risk for RA focused on the progression from arthralgia to RA, since (early) identification of individuals that will develop RA is a key point from a clinician’s perspective. However, there is also a group of patients that were considered at risk for RA but over time do not develop RA, meaning that, in hindsight, they possibly have not been truly ‘pre-RA’. This subgroup of patients is unexplored, and the course and outcome of joint symptoms and subclinical inflammation in these patients are yet unknown,” Robin M. ten Brinck and colleagues at Leiden wrote in Arthritis Research & Therapy.

The researchers followed 152 patients with clinically suspicious arthralgia (CSA) who did not develop RA during 2 years of follow-up. All patients had complete clinical data, and 98 had complete 2-year MRI data. Most of the 152 patients were women (74%), and they had a mean age of 47 years, a median of 5 tender joints (out of 68 evaluated), and 19% carried RA-related autoantibodies (rheumatoid factor and/or anti–citrullinated peptide antibody). None of the patients received disease-modifying antirheumatic drugs or glucocorticoids during the study; only NSAIDs were allowed.

Overall, 57 (38%) of the 152 reported resolution of symptoms by 2 years, including 32 (33%) of the 98 patients with serial MRI results available at 2 years. Of the remaining 95 patients who continued to have symptoms, 43 were diagnosed as having persistent CSA, 10 had osteoarthritis, and 13 had tendinomuscular complaints.

There was no statistically significant difference in mean baseline total MRI inflammation scores between those with and without symptom resolution, but among patients with a mean total MRI inflammation score greater than 0 at baseline, those who achieved resolution of symptoms over time had a mean score higher than that of symptom-free patients at baseline. Those patients with resolved symptoms also had a statistically significant decrease in MRI inflammation score at the 2-year follow-up. A smaller and not statistically significant decline in total MRI score was seen in patients without symptom resolution.

“Our study is the first to quantify the percentage of patients presenting with CSA that will have a resolution of symptoms over time. It consists of one-third of all nonprogressing patients and 27% of all patients that were identified as having CSA by rheumatologists,” the researchers wrote.

The study was sponsored by the European Research Council. The authors had no relevant disclosures.

jevans@mdedge.com

SOURCE: ten Brinck RM et al. Arthritis Res Ther. 2020 Jan 16. doi: 10.1186/s13075-020-2102-9.

The staff of MDedge Rheumatology/Rheumatology News are happy to announce that Melissa S. Oliver, MD, and C. Kent Kwoh, MD, have joined the editorial advisory board.

Dr. Oliver is an assistant professor of clinical pediatrics in the department of pediatric rheumatology at Indiana University and practices at Riley Hospital for Children, both in Indianapolis. She completed her training in pediatrics at New Jersey Medical School, Newark, and Pediatric Rheumatology at Stanford (Calif.) University.

Her research interests include improving patient outcomes in the juvenile spondyloarthropathy and chronic nonbacterial osteomyelitis populations. She is an active member of the Childhood Arthritis & Rheumatology Research Alliance.

Dr. Kwoh is director of the University of Arizona Arthritis Center, Tucson. He holds the Charles A.L. and Suzanne M. Stephens Endowed Chair in Rheumatology and is the chief of the division of rheumatology and professor of medicine and medical imaging at the university.

His current major research interests focus on the identification of biomarkers – most notably MRI imaging biomarkers for the development and/or progression of knee OA and the characterization of knee pain patterns in OA. He also has a major interest in the reduction and ultimately the elimination of disparities in the management of arthritis and musculoskeletal diseases.

jevans@mdedge.com

The staff of MDedge Rheumatology/Rheumatology News are happy to announce that Melissa S. Oliver, MD, and C. Kent Kwoh, MD, have joined the editorial advisory board.

Dr. Oliver is an assistant professor of clinical pediatrics in the department of pediatric rheumatology at Indiana University and practices at Riley Hospital for Children, both in Indianapolis. She completed her training in pediatrics at New Jersey Medical School, Newark, and Pediatric Rheumatology at Stanford (Calif.) University.

Her research interests include improving patient outcomes in the juvenile spondyloarthropathy and chronic nonbacterial osteomyelitis populations. She is an active member of the Childhood Arthritis & Rheumatology Research Alliance.

Dr. Kwoh is director of the University of Arizona Arthritis Center, Tucson. He holds the Charles A.L. and Suzanne M. Stephens Endowed Chair in Rheumatology and is the chief of the division of rheumatology and professor of medicine and medical imaging at the university.

His current major research interests focus on the identification of biomarkers – most notably MRI imaging biomarkers for the development and/or progression of knee OA and the characterization of knee pain patterns in OA. He also has a major interest in the reduction and ultimately the elimination of disparities in the management of arthritis and musculoskeletal diseases.

jevans@mdedge.com

The staff of MDedge Rheumatology/Rheumatology News are happy to announce that Melissa S. Oliver, MD, and C. Kent Kwoh, MD, have joined the editorial advisory board.

Dr. Oliver is an assistant professor of clinical pediatrics in the department of pediatric rheumatology at Indiana University and practices at Riley Hospital for Children, both in Indianapolis. She completed her training in pediatrics at New Jersey Medical School, Newark, and Pediatric Rheumatology at Stanford (Calif.) University.

Her research interests include improving patient outcomes in the juvenile spondyloarthropathy and chronic nonbacterial osteomyelitis populations. She is an active member of the Childhood Arthritis & Rheumatology Research Alliance.

Dr. Kwoh is director of the University of Arizona Arthritis Center, Tucson. He holds the Charles A.L. and Suzanne M. Stephens Endowed Chair in Rheumatology and is the chief of the division of rheumatology and professor of medicine and medical imaging at the university.

His current major research interests focus on the identification of biomarkers – most notably MRI imaging biomarkers for the development and/or progression of knee OA and the characterization of knee pain patterns in OA. He also has a major interest in the reduction and ultimately the elimination of disparities in the management of arthritis and musculoskeletal diseases.

jevans@mdedge.com