User login
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.
Peripheral nervous system events have lasting impact on SLE patients
Peripheral nervous system disease, predominantly neuropathies, constitutes a substantial proportion of the manifestations of neuropsychiatric systemic lupus erythematosus (SLE) and has a lasting negative impact on health-related quality of life, John G. Hanly, MD, of Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, N.S., and associates reported in Arthritis & Rheumatology.
According to the study of 1,827 SLE patients who had been recently diagnosed and enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) network at sites in Europe, Asia, and North America during 1999-2011, 161 peripheral nervous system (PNS) events occurred in 139 of the patients (8%) over a mean 7.6 years of follow-up.
Using the seven American College of Rheumatology case definitions for PNS disease in neuropsychiatric SLE, most of the events were peripheral neuropathy (41%), mononeuropathy (27%), and cranial neuropathy (24%). For 110 with peripheral neuropathy or mononeuropathy who underwent electrophysiologic testing, axonal damage was often present (42%), followed by demyelination (22%).
The PNS events were attributed to SLE in about 58%-75% of the patients. Based on these data the investigators estimated that after 10 years the cumulative incidence of any PNS event regardless of its attribution was about 9%, and it was nearly 7% for events attributed to SLE.
The probability that the neuropathies would not resolve over time was estimated at about 43% for peripheral neuropathy, 29% for mononeuropathy, and 30% for cranial neuropathy. Resolution of neuropathy was most rapid for cranial neuropathy, followed by mononeuropathy and peripheral neuropathy.
Patients with PNS events had significantly lower physical and mental health component scores on the 36-item Short Form Health Survey than did patients without a neuropsychiatric event up to the study assessment, and these differences persisted for 10 years of follow-up.
These “findings provide a benchmark for the assessment of future treatment modalities,” the investigators concluded.
SOURCE: Hanly JG et al. Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41070.
Peripheral nervous system disease, predominantly neuropathies, constitutes a substantial proportion of the manifestations of neuropsychiatric systemic lupus erythematosus (SLE) and has a lasting negative impact on health-related quality of life, John G. Hanly, MD, of Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, N.S., and associates reported in Arthritis & Rheumatology.
According to the study of 1,827 SLE patients who had been recently diagnosed and enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) network at sites in Europe, Asia, and North America during 1999-2011, 161 peripheral nervous system (PNS) events occurred in 139 of the patients (8%) over a mean 7.6 years of follow-up.
Using the seven American College of Rheumatology case definitions for PNS disease in neuropsychiatric SLE, most of the events were peripheral neuropathy (41%), mononeuropathy (27%), and cranial neuropathy (24%). For 110 with peripheral neuropathy or mononeuropathy who underwent electrophysiologic testing, axonal damage was often present (42%), followed by demyelination (22%).
The PNS events were attributed to SLE in about 58%-75% of the patients. Based on these data the investigators estimated that after 10 years the cumulative incidence of any PNS event regardless of its attribution was about 9%, and it was nearly 7% for events attributed to SLE.
The probability that the neuropathies would not resolve over time was estimated at about 43% for peripheral neuropathy, 29% for mononeuropathy, and 30% for cranial neuropathy. Resolution of neuropathy was most rapid for cranial neuropathy, followed by mononeuropathy and peripheral neuropathy.
Patients with PNS events had significantly lower physical and mental health component scores on the 36-item Short Form Health Survey than did patients without a neuropsychiatric event up to the study assessment, and these differences persisted for 10 years of follow-up.
These “findings provide a benchmark for the assessment of future treatment modalities,” the investigators concluded.
SOURCE: Hanly JG et al. Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41070.
Peripheral nervous system disease, predominantly neuropathies, constitutes a substantial proportion of the manifestations of neuropsychiatric systemic lupus erythematosus (SLE) and has a lasting negative impact on health-related quality of life, John G. Hanly, MD, of Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, N.S., and associates reported in Arthritis & Rheumatology.
According to the study of 1,827 SLE patients who had been recently diagnosed and enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) network at sites in Europe, Asia, and North America during 1999-2011, 161 peripheral nervous system (PNS) events occurred in 139 of the patients (8%) over a mean 7.6 years of follow-up.
Using the seven American College of Rheumatology case definitions for PNS disease in neuropsychiatric SLE, most of the events were peripheral neuropathy (41%), mononeuropathy (27%), and cranial neuropathy (24%). For 110 with peripheral neuropathy or mononeuropathy who underwent electrophysiologic testing, axonal damage was often present (42%), followed by demyelination (22%).
The PNS events were attributed to SLE in about 58%-75% of the patients. Based on these data the investigators estimated that after 10 years the cumulative incidence of any PNS event regardless of its attribution was about 9%, and it was nearly 7% for events attributed to SLE.
The probability that the neuropathies would not resolve over time was estimated at about 43% for peripheral neuropathy, 29% for mononeuropathy, and 30% for cranial neuropathy. Resolution of neuropathy was most rapid for cranial neuropathy, followed by mononeuropathy and peripheral neuropathy.
Patients with PNS events had significantly lower physical and mental health component scores on the 36-item Short Form Health Survey than did patients without a neuropsychiatric event up to the study assessment, and these differences persisted for 10 years of follow-up.
These “findings provide a benchmark for the assessment of future treatment modalities,” the investigators concluded.
SOURCE: Hanly JG et al. Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41070.
REPORTING FROM ARTHRITIS & RHEUMATOLOGY
Hadlima approved as fourth adalimumab biosimilar in U.S.
The Food and Drug Administration has approved the Humira biosimilar Hadlima (adalimumab-bwwd), making it the fourth adalimumab biosimilar approved in the United States, the agency announced.
Hadlima is approved for seven of the reference product’s indications, which include rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, and ulcerative colitis.
The product will launch in the United States on June 30, 2023. Other FDA-approved adalimumab biosimilars – Amjevita (adalimunab-atto), Cyltezo (adalimumab-adbm), Hyrimoz (adalimumab-adaz) – similarly will not reach the U.S. market until 2023.
Hadlima is developed by Samsung Bioepis and commercialized by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.
Visit the AGA GI Patient Center for information to share with your patients about biologics and biosimilars at https://www.gastro.org/practice-guidance/gi-patient-center/topic/biosimilars.
The Food and Drug Administration has approved the Humira biosimilar Hadlima (adalimumab-bwwd), making it the fourth adalimumab biosimilar approved in the United States, the agency announced.
Hadlima is approved for seven of the reference product’s indications, which include rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, and ulcerative colitis.
The product will launch in the United States on June 30, 2023. Other FDA-approved adalimumab biosimilars – Amjevita (adalimunab-atto), Cyltezo (adalimumab-adbm), Hyrimoz (adalimumab-adaz) – similarly will not reach the U.S. market until 2023.
Hadlima is developed by Samsung Bioepis and commercialized by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.
Visit the AGA GI Patient Center for information to share with your patients about biologics and biosimilars at https://www.gastro.org/practice-guidance/gi-patient-center/topic/biosimilars.
The Food and Drug Administration has approved the Humira biosimilar Hadlima (adalimumab-bwwd), making it the fourth adalimumab biosimilar approved in the United States, the agency announced.
Hadlima is approved for seven of the reference product’s indications, which include rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, and ulcerative colitis.
The product will launch in the United States on June 30, 2023. Other FDA-approved adalimumab biosimilars – Amjevita (adalimunab-atto), Cyltezo (adalimumab-adbm), Hyrimoz (adalimumab-adaz) – similarly will not reach the U.S. market until 2023.
Hadlima is developed by Samsung Bioepis and commercialized by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.
Visit the AGA GI Patient Center for information to share with your patients about biologics and biosimilars at https://www.gastro.org/practice-guidance/gi-patient-center/topic/biosimilars.
Hadlima approved as fourth adalimumab biosimilar in U.S.
The Food and Drug Administration has approved the Humira biosimilar Hadlima (adalimumab-bwwd), making it the fourth adalimumab biosimilar approved in the United States, the agency announced.
Hadlima is approved for seven of the reference product’s indications, which include rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, and ulcerative colitis.
The product will launch in the United States on June 30, 2023. Other FDA-approved adalimumab biosimilars – Amjevita (adalimunab-atto), Cyltezo (adalimumab-adbm), Hyrimoz (adalimumab-adaz) – similarly will not reach the U.S. market until 2023.
Hadlima is developed by Samsung Bioepis and commercialized by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.
*This article was updated on July 24, 2019.
The Food and Drug Administration has approved the Humira biosimilar Hadlima (adalimumab-bwwd), making it the fourth adalimumab biosimilar approved in the United States, the agency announced.
Hadlima is approved for seven of the reference product’s indications, which include rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, and ulcerative colitis.
The product will launch in the United States on June 30, 2023. Other FDA-approved adalimumab biosimilars – Amjevita (adalimunab-atto), Cyltezo (adalimumab-adbm), Hyrimoz (adalimumab-adaz) – similarly will not reach the U.S. market until 2023.
Hadlima is developed by Samsung Bioepis and commercialized by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.
*This article was updated on July 24, 2019.
The Food and Drug Administration has approved the Humira biosimilar Hadlima (adalimumab-bwwd), making it the fourth adalimumab biosimilar approved in the United States, the agency announced.
Hadlima is approved for seven of the reference product’s indications, which include rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, and ulcerative colitis.
The product will launch in the United States on June 30, 2023. Other FDA-approved adalimumab biosimilars – Amjevita (adalimunab-atto), Cyltezo (adalimumab-adbm), Hyrimoz (adalimumab-adaz) – similarly will not reach the U.S. market until 2023.
Hadlima is developed by Samsung Bioepis and commercialized by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.
*This article was updated on July 24, 2019.
Huntington’s symptom domains correlate with structural differences
Differences in the prominence of motor, cognitive, and psychiatric symptoms of Huntington’s disease among individuals can be attributed to differences in gray and white matter structural alterations, according to a neuroimaging study of 43 Huntington’s disease gene carriers conducted by Clara Garcia-Gorro, PhD, of the Bellvitge Institute for Biomedical Research and Bellvitge Hospital, Barcelona, and colleagues.
Their work detected a common neurobiological basis for the carriers’ cognitive and motor symptoms in patterns of reductions in gray matter, cortical thickness, and white matter integrity in cognitive and motor networks. They also found that depressive symptoms were associated with imaging findings primarily characterized by reduced cortical thickness in limbic and paralimbic regions.
“These results are relevant in the context of clinical trials, since they could be used to define specific biomarkers for each symptom profile, even before clinical signs appear. Having more homogeneous groups would potentially increase the likelihood of detecting successful interventions and help to find individualized treatments that target specific cognitive, motor, and psychiatric disturbances,” the authors concluded.
SOURCE: Garcia-Gorro C et al. Neuroimage Clin. 2019 Jun 15. doi: 10.1016/j.nicl.2019.101900.
Differences in the prominence of motor, cognitive, and psychiatric symptoms of Huntington’s disease among individuals can be attributed to differences in gray and white matter structural alterations, according to a neuroimaging study of 43 Huntington’s disease gene carriers conducted by Clara Garcia-Gorro, PhD, of the Bellvitge Institute for Biomedical Research and Bellvitge Hospital, Barcelona, and colleagues.
Their work detected a common neurobiological basis for the carriers’ cognitive and motor symptoms in patterns of reductions in gray matter, cortical thickness, and white matter integrity in cognitive and motor networks. They also found that depressive symptoms were associated with imaging findings primarily characterized by reduced cortical thickness in limbic and paralimbic regions.
“These results are relevant in the context of clinical trials, since they could be used to define specific biomarkers for each symptom profile, even before clinical signs appear. Having more homogeneous groups would potentially increase the likelihood of detecting successful interventions and help to find individualized treatments that target specific cognitive, motor, and psychiatric disturbances,” the authors concluded.
SOURCE: Garcia-Gorro C et al. Neuroimage Clin. 2019 Jun 15. doi: 10.1016/j.nicl.2019.101900.
Differences in the prominence of motor, cognitive, and psychiatric symptoms of Huntington’s disease among individuals can be attributed to differences in gray and white matter structural alterations, according to a neuroimaging study of 43 Huntington’s disease gene carriers conducted by Clara Garcia-Gorro, PhD, of the Bellvitge Institute for Biomedical Research and Bellvitge Hospital, Barcelona, and colleagues.
Their work detected a common neurobiological basis for the carriers’ cognitive and motor symptoms in patterns of reductions in gray matter, cortical thickness, and white matter integrity in cognitive and motor networks. They also found that depressive symptoms were associated with imaging findings primarily characterized by reduced cortical thickness in limbic and paralimbic regions.
“These results are relevant in the context of clinical trials, since they could be used to define specific biomarkers for each symptom profile, even before clinical signs appear. Having more homogeneous groups would potentially increase the likelihood of detecting successful interventions and help to find individualized treatments that target specific cognitive, motor, and psychiatric disturbances,” the authors concluded.
SOURCE: Garcia-Gorro C et al. Neuroimage Clin. 2019 Jun 15. doi: 10.1016/j.nicl.2019.101900.
FROM NEUROIMAGE: CLINICAL
Efforts toward producing CNO/CRMO classification criteria show first results
MADRID – according to recent findings from international surveys of pediatric rheumatologists that were presented at the European Congress of Rheumatology.
Melissa Oliver, MD, a pediatric rheumatologist at Riley Hospital for Children, Indianapolis, and colleagues recently undertook the multiphase study as part of an international collaborative effort led by the Childhood Arthritis and Rheumatology Research Alliance to establish consensus-based diagnostic and classification criteria for CNO, an autoinflammatory bone disease of unknown cause that primarily affects children and adolescents. CNO is also known as chronic recurrent multifocal osteomyelitis (CRMO). If this disease is not diagnosed and treated appropriately in a timely fashion, damage and long-term disability is possible. In the absence of widely accepted, consensus-driven criteria, treatment is based largely on expert opinion, Dr. Oliver explained in an interview.
“There is an urgent need for a new and more robust set of classification criteria for CRMO, based on large expert consensus and the analysis of a large sample of patients and controls,” she said.
There are two proposed diagnostic criteria, the 2007 classification of nonbacterial osteitis and the 2016 Bristol diagnostic criteria for CRMO, but both are derived from single-center cohort studies and have not been validated, Dr. Oliver explained.
The list of candidate items that have come out of the study is moving clinicians a step closer toward the design of a practical patient data collection form that appropriately weighs each item included in the classification criteria.
The study employed anonymous survey and nominal group techniques with the goal of developing a set of classification criteria sensitive and specific enough to identify CRMO/CNO patients. In phase 1, a Delphi survey was administered among international rheumatologists to generate candidate criteria items. Phase 2 sought to reduce candidate criteria items through consensus processes via input from physicians managing CNO and patients or caregivers of children with CNO.
Altogether, 259 of 865 pediatric rheumatologists (30%) completed an online questionnaire addressing features key to the classification of CNO, including 77 who practice in Europe (30%), 132 in North America (51%), and 50 on other continents (19%). Of these, 138 (53%) had greater than 10 years of clinical practice experience, and 108 (42%) had managed more than 10 CNO patients.
Initially, Dr. Oliver and colleagues identified 33 candidate criteria items that fell into six domains: clinical presentation, physical exam, laboratory findings, imaging findings, bone biopsy, and treatment response. The top eight weighted items that increased the likelihood of CNO/CRMO were exclusion of malignancy by bone biopsy; multifocal bone lesions; presence of bone pain, swelling, and/or warmth; signs of fibrosis and/or inflammation on bone biopsy; typical location of CNO/CRMO lesion, such as the clavicle, metaphysis of long bones, the mandible, and vertebrae; presence of CNO/CRMO–related comorbidities; normal C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR); and typical MRI findings of CNO/CRMO.
By phase 2, candidate items, which were presented to 39 rheumatologists and 7 parents, were refined or eliminated using item-reduction techniques. A second survey was issued to 77 of 82 members of a work group so that the remaining items could be ranked by their power of distinguishing CNO from conditions that merely mimicked the disease. The greatest mean discriminatory scores were identified with multifocal lesions (ruling out malignancy and infection) and typical location on imaging. Normal C-reactive protein and/or an erythrocyte sedimentation rate more than three times the upper limit of normal had the greatest negative mean discriminatory scores.
The next steps will be to form an expert panel who will use 1000minds software to determine the final criteria and identify a threshold for disease. The investigators hope to build a large multinational case repository of at least 500 patients with CNO/CRMO and 500 patients with mimicking conditions from which to derive a development cohort and an external validation cohort. So far, 10 sites, including 4 in Europe, have obtained approval from an institutional review board. The group has also submitted a proposal for classification criteria to the American College of Rheumatology and the European League Against Rheumatism, Dr. Oliver said.
Dr. Oliver had no disclosures to report, but several coauthors reported financial ties to industry.
SOURCE: Oliver M et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):254-5, Abstract OP0342. doi: 10.1136/annrheumdis-2019-eular.1539.
MADRID – according to recent findings from international surveys of pediatric rheumatologists that were presented at the European Congress of Rheumatology.
Melissa Oliver, MD, a pediatric rheumatologist at Riley Hospital for Children, Indianapolis, and colleagues recently undertook the multiphase study as part of an international collaborative effort led by the Childhood Arthritis and Rheumatology Research Alliance to establish consensus-based diagnostic and classification criteria for CNO, an autoinflammatory bone disease of unknown cause that primarily affects children and adolescents. CNO is also known as chronic recurrent multifocal osteomyelitis (CRMO). If this disease is not diagnosed and treated appropriately in a timely fashion, damage and long-term disability is possible. In the absence of widely accepted, consensus-driven criteria, treatment is based largely on expert opinion, Dr. Oliver explained in an interview.
“There is an urgent need for a new and more robust set of classification criteria for CRMO, based on large expert consensus and the analysis of a large sample of patients and controls,” she said.
There are two proposed diagnostic criteria, the 2007 classification of nonbacterial osteitis and the 2016 Bristol diagnostic criteria for CRMO, but both are derived from single-center cohort studies and have not been validated, Dr. Oliver explained.
The list of candidate items that have come out of the study is moving clinicians a step closer toward the design of a practical patient data collection form that appropriately weighs each item included in the classification criteria.
The study employed anonymous survey and nominal group techniques with the goal of developing a set of classification criteria sensitive and specific enough to identify CRMO/CNO patients. In phase 1, a Delphi survey was administered among international rheumatologists to generate candidate criteria items. Phase 2 sought to reduce candidate criteria items through consensus processes via input from physicians managing CNO and patients or caregivers of children with CNO.
Altogether, 259 of 865 pediatric rheumatologists (30%) completed an online questionnaire addressing features key to the classification of CNO, including 77 who practice in Europe (30%), 132 in North America (51%), and 50 on other continents (19%). Of these, 138 (53%) had greater than 10 years of clinical practice experience, and 108 (42%) had managed more than 10 CNO patients.
Initially, Dr. Oliver and colleagues identified 33 candidate criteria items that fell into six domains: clinical presentation, physical exam, laboratory findings, imaging findings, bone biopsy, and treatment response. The top eight weighted items that increased the likelihood of CNO/CRMO were exclusion of malignancy by bone biopsy; multifocal bone lesions; presence of bone pain, swelling, and/or warmth; signs of fibrosis and/or inflammation on bone biopsy; typical location of CNO/CRMO lesion, such as the clavicle, metaphysis of long bones, the mandible, and vertebrae; presence of CNO/CRMO–related comorbidities; normal C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR); and typical MRI findings of CNO/CRMO.
By phase 2, candidate items, which were presented to 39 rheumatologists and 7 parents, were refined or eliminated using item-reduction techniques. A second survey was issued to 77 of 82 members of a work group so that the remaining items could be ranked by their power of distinguishing CNO from conditions that merely mimicked the disease. The greatest mean discriminatory scores were identified with multifocal lesions (ruling out malignancy and infection) and typical location on imaging. Normal C-reactive protein and/or an erythrocyte sedimentation rate more than three times the upper limit of normal had the greatest negative mean discriminatory scores.
The next steps will be to form an expert panel who will use 1000minds software to determine the final criteria and identify a threshold for disease. The investigators hope to build a large multinational case repository of at least 500 patients with CNO/CRMO and 500 patients with mimicking conditions from which to derive a development cohort and an external validation cohort. So far, 10 sites, including 4 in Europe, have obtained approval from an institutional review board. The group has also submitted a proposal for classification criteria to the American College of Rheumatology and the European League Against Rheumatism, Dr. Oliver said.
Dr. Oliver had no disclosures to report, but several coauthors reported financial ties to industry.
SOURCE: Oliver M et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):254-5, Abstract OP0342. doi: 10.1136/annrheumdis-2019-eular.1539.
MADRID – according to recent findings from international surveys of pediatric rheumatologists that were presented at the European Congress of Rheumatology.
Melissa Oliver, MD, a pediatric rheumatologist at Riley Hospital for Children, Indianapolis, and colleagues recently undertook the multiphase study as part of an international collaborative effort led by the Childhood Arthritis and Rheumatology Research Alliance to establish consensus-based diagnostic and classification criteria for CNO, an autoinflammatory bone disease of unknown cause that primarily affects children and adolescents. CNO is also known as chronic recurrent multifocal osteomyelitis (CRMO). If this disease is not diagnosed and treated appropriately in a timely fashion, damage and long-term disability is possible. In the absence of widely accepted, consensus-driven criteria, treatment is based largely on expert opinion, Dr. Oliver explained in an interview.
“There is an urgent need for a new and more robust set of classification criteria for CRMO, based on large expert consensus and the analysis of a large sample of patients and controls,” she said.
There are two proposed diagnostic criteria, the 2007 classification of nonbacterial osteitis and the 2016 Bristol diagnostic criteria for CRMO, but both are derived from single-center cohort studies and have not been validated, Dr. Oliver explained.
The list of candidate items that have come out of the study is moving clinicians a step closer toward the design of a practical patient data collection form that appropriately weighs each item included in the classification criteria.
The study employed anonymous survey and nominal group techniques with the goal of developing a set of classification criteria sensitive and specific enough to identify CRMO/CNO patients. In phase 1, a Delphi survey was administered among international rheumatologists to generate candidate criteria items. Phase 2 sought to reduce candidate criteria items through consensus processes via input from physicians managing CNO and patients or caregivers of children with CNO.
Altogether, 259 of 865 pediatric rheumatologists (30%) completed an online questionnaire addressing features key to the classification of CNO, including 77 who practice in Europe (30%), 132 in North America (51%), and 50 on other continents (19%). Of these, 138 (53%) had greater than 10 years of clinical practice experience, and 108 (42%) had managed more than 10 CNO patients.
Initially, Dr. Oliver and colleagues identified 33 candidate criteria items that fell into six domains: clinical presentation, physical exam, laboratory findings, imaging findings, bone biopsy, and treatment response. The top eight weighted items that increased the likelihood of CNO/CRMO were exclusion of malignancy by bone biopsy; multifocal bone lesions; presence of bone pain, swelling, and/or warmth; signs of fibrosis and/or inflammation on bone biopsy; typical location of CNO/CRMO lesion, such as the clavicle, metaphysis of long bones, the mandible, and vertebrae; presence of CNO/CRMO–related comorbidities; normal C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR); and typical MRI findings of CNO/CRMO.
By phase 2, candidate items, which were presented to 39 rheumatologists and 7 parents, were refined or eliminated using item-reduction techniques. A second survey was issued to 77 of 82 members of a work group so that the remaining items could be ranked by their power of distinguishing CNO from conditions that merely mimicked the disease. The greatest mean discriminatory scores were identified with multifocal lesions (ruling out malignancy and infection) and typical location on imaging. Normal C-reactive protein and/or an erythrocyte sedimentation rate more than three times the upper limit of normal had the greatest negative mean discriminatory scores.
The next steps will be to form an expert panel who will use 1000minds software to determine the final criteria and identify a threshold for disease. The investigators hope to build a large multinational case repository of at least 500 patients with CNO/CRMO and 500 patients with mimicking conditions from which to derive a development cohort and an external validation cohort. So far, 10 sites, including 4 in Europe, have obtained approval from an institutional review board. The group has also submitted a proposal for classification criteria to the American College of Rheumatology and the European League Against Rheumatism, Dr. Oliver said.
Dr. Oliver had no disclosures to report, but several coauthors reported financial ties to industry.
SOURCE: Oliver M et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):254-5, Abstract OP0342. doi: 10.1136/annrheumdis-2019-eular.1539.
REPORTING FROM EULAR 2019 CONGRESS
Bisphosphonates before denosumab may prevent postdenosumab BMD rebound effect
MADRID – Results from an ongoing study of postmenopausal women who discontinue osteoporosis treatment with denosumab (Prolia) so far support the use of denosumab as a second-line therapy after a bisphosphonate, unless otherwise indicated, in order to reduce the loss of bone mineral density (BMD) after its discontinuation and also to support treatment to reduce bone turnover biomarkers as much as possible after stopping denosumab.
“We saw in our study that, even if you give bisphosphonates after denosumab discontinuation, [patients] could lose bone, and the group that controlled the loss of bone had very high control of bone turnover markers,” study author and presenter Bérengère Rozier Aubry, MD, said in an interview at the European Congress of Rheumatology.
She and her colleagues at the Center of Bone Diseases at Lausanne (Switzerland) University Hospital are conducting the ReoLaus (Rebound Effect Observatory in Lausanne) Bone Project to determine whether giving a bisphosphonate to postmenopausal women with osteoporosis after they have discontinued denosumab can stop the loss of bone mineral density (BMD) observed in many patients up to 2 years after stopping denosumab. This postdenosumab BMD loss has also been observed to occur with multiple spontaneous vertebral fractures.
Nearly half of patients who start denosumab discontinue it within 1 year, and 64% by 2 years, according to U.S. administrative claims data (Osteoporos Int. 2017 Apr. doi: 10.1007/s00198-016-3886-y), even though it can be taken for up to 10 years. The discontinuation is either because the patient wishes to do so or there’s a medical indication such as stopping aromatase inhibitor treatment, resolution of osteoporosis, or side effects, Dr. Rozier Aubry said in a press conference at the European Congress of Rheumatology.
Upon discontinuing denosumab, there’s a marked rebound effect in which levels of bone turnover markers rise for 2 years, and some or all of the BMD that was gained is lost (J Clin Endocrinol Metab. 2011 Apr. doi: 10.1210/jc.2010-1502). Multiple spontaneous vertebral fractures also have been reported in 5%-7%, as Dr. Rozier Aubry and colleagues first described in 2016 (Osteoporos Int. 2016 May. doi: 10.1007/s00198-015-3380-y) and others have reported subsequently.
Recommendations from the Endocrine Society in March 2019, a 2017 position statement from the European Calcified Tissue Society, and guidelines from other groups advise giving antiresorptive treatment (bisphosphonates, hormone therapy, or selective estrogen-receptor modulators) but do not say which one, in what dose, when, or for how long, Dr. Rozier Aubry noted.
Treatment with zoledronate 6 months after the last denosumab injection achieves partial preservation of BMD, but multiple vertebral fractures have still been reported when raloxifene, ibandronate, or alendronate have been given after stopping denosumab, she said.
In the ReoLaus Bone Project, Dr. Rozier Aubry and associates are following 170 postmenopausal women with osteoporosis at Lausanne University Hospital who are taking denosumab therapy. At the congress, she reported on the first 71 women in the cohort with 1 year of follow-up. They had a mean age of 64 years, had fewer than one prevalent fracture before starting denosumab, and stopped denosumab after a mean of 7.7 injections. Overall, 8% took glucocorticoids, and 22% took aromatase inhibitors.
The investigators collected data on what treatment was used after denosumab, how bone turnover markers changed 1-3 months after the last denosumab injection and then regularly afterward, how bone mineral density changed after 1 year, and any new osteoporotic fractures.
At the time of denosumab discontinuation, 59% received zoledronate, 24% alendronate, 3% other drugs, and 14% nothing. At a mean of about 17 months after the last denosumab injection, the investigators classified 30 patients as BMD losers (losing at least 3.96%), and 41 had stable BMD. The researchers found that BMD losers were younger (61.4 years vs. 65.5 years), were less likely to use zoledronate before starting denosumab (0% vs. 12%), and had greater serum CTX (C-telopeptide cross-linked type 1 collagen) levels at denosumab initiation (644 ng/mL vs. 474 ng/mL) and 12.8 months after stopping denosumab (592 ng/mL vs. 336 ng/mL) than did those with stable BMD. All differences were statistically significant.
“Our results support the use of denosumab in second line after bisphosphonate therapy to restrain the BMD loss at its discontinuation ... and a strategy to maintain the bone turnover marker serum CTX as low as possible after denosumab discontinuation,” she concluded.
“Our proposition is to start with 1 or 2 years of bisphosphonates, and if the osteoporosis is severe, to switch to denosumab treatment for 4, 6 years. … We can use denosumab for 10 years without side effects, and after that we give bisphosphonates to consolidate the treatment,” she said.
Dr. Rozier Aubry and her associates plan to follow patients in their study for 2 years.
Dr. Rozier Aubry disclosed serving on speakers bureaus for Eli Lilly, Pfizer, Amgen, and Novartis.
SOURCE: Rozier Aubry B et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):115; Abstract OP0085. doi: 10.1136/annrheumdis-2019-eular.4175.
MADRID – Results from an ongoing study of postmenopausal women who discontinue osteoporosis treatment with denosumab (Prolia) so far support the use of denosumab as a second-line therapy after a bisphosphonate, unless otherwise indicated, in order to reduce the loss of bone mineral density (BMD) after its discontinuation and also to support treatment to reduce bone turnover biomarkers as much as possible after stopping denosumab.
“We saw in our study that, even if you give bisphosphonates after denosumab discontinuation, [patients] could lose bone, and the group that controlled the loss of bone had very high control of bone turnover markers,” study author and presenter Bérengère Rozier Aubry, MD, said in an interview at the European Congress of Rheumatology.
She and her colleagues at the Center of Bone Diseases at Lausanne (Switzerland) University Hospital are conducting the ReoLaus (Rebound Effect Observatory in Lausanne) Bone Project to determine whether giving a bisphosphonate to postmenopausal women with osteoporosis after they have discontinued denosumab can stop the loss of bone mineral density (BMD) observed in many patients up to 2 years after stopping denosumab. This postdenosumab BMD loss has also been observed to occur with multiple spontaneous vertebral fractures.
Nearly half of patients who start denosumab discontinue it within 1 year, and 64% by 2 years, according to U.S. administrative claims data (Osteoporos Int. 2017 Apr. doi: 10.1007/s00198-016-3886-y), even though it can be taken for up to 10 years. The discontinuation is either because the patient wishes to do so or there’s a medical indication such as stopping aromatase inhibitor treatment, resolution of osteoporosis, or side effects, Dr. Rozier Aubry said in a press conference at the European Congress of Rheumatology.
Upon discontinuing denosumab, there’s a marked rebound effect in which levels of bone turnover markers rise for 2 years, and some or all of the BMD that was gained is lost (J Clin Endocrinol Metab. 2011 Apr. doi: 10.1210/jc.2010-1502). Multiple spontaneous vertebral fractures also have been reported in 5%-7%, as Dr. Rozier Aubry and colleagues first described in 2016 (Osteoporos Int. 2016 May. doi: 10.1007/s00198-015-3380-y) and others have reported subsequently.
Recommendations from the Endocrine Society in March 2019, a 2017 position statement from the European Calcified Tissue Society, and guidelines from other groups advise giving antiresorptive treatment (bisphosphonates, hormone therapy, or selective estrogen-receptor modulators) but do not say which one, in what dose, when, or for how long, Dr. Rozier Aubry noted.
Treatment with zoledronate 6 months after the last denosumab injection achieves partial preservation of BMD, but multiple vertebral fractures have still been reported when raloxifene, ibandronate, or alendronate have been given after stopping denosumab, she said.
In the ReoLaus Bone Project, Dr. Rozier Aubry and associates are following 170 postmenopausal women with osteoporosis at Lausanne University Hospital who are taking denosumab therapy. At the congress, she reported on the first 71 women in the cohort with 1 year of follow-up. They had a mean age of 64 years, had fewer than one prevalent fracture before starting denosumab, and stopped denosumab after a mean of 7.7 injections. Overall, 8% took glucocorticoids, and 22% took aromatase inhibitors.
The investigators collected data on what treatment was used after denosumab, how bone turnover markers changed 1-3 months after the last denosumab injection and then regularly afterward, how bone mineral density changed after 1 year, and any new osteoporotic fractures.
At the time of denosumab discontinuation, 59% received zoledronate, 24% alendronate, 3% other drugs, and 14% nothing. At a mean of about 17 months after the last denosumab injection, the investigators classified 30 patients as BMD losers (losing at least 3.96%), and 41 had stable BMD. The researchers found that BMD losers were younger (61.4 years vs. 65.5 years), were less likely to use zoledronate before starting denosumab (0% vs. 12%), and had greater serum CTX (C-telopeptide cross-linked type 1 collagen) levels at denosumab initiation (644 ng/mL vs. 474 ng/mL) and 12.8 months after stopping denosumab (592 ng/mL vs. 336 ng/mL) than did those with stable BMD. All differences were statistically significant.
“Our results support the use of denosumab in second line after bisphosphonate therapy to restrain the BMD loss at its discontinuation ... and a strategy to maintain the bone turnover marker serum CTX as low as possible after denosumab discontinuation,” she concluded.
“Our proposition is to start with 1 or 2 years of bisphosphonates, and if the osteoporosis is severe, to switch to denosumab treatment for 4, 6 years. … We can use denosumab for 10 years without side effects, and after that we give bisphosphonates to consolidate the treatment,” she said.
Dr. Rozier Aubry and her associates plan to follow patients in their study for 2 years.
Dr. Rozier Aubry disclosed serving on speakers bureaus for Eli Lilly, Pfizer, Amgen, and Novartis.
SOURCE: Rozier Aubry B et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):115; Abstract OP0085. doi: 10.1136/annrheumdis-2019-eular.4175.
MADRID – Results from an ongoing study of postmenopausal women who discontinue osteoporosis treatment with denosumab (Prolia) so far support the use of denosumab as a second-line therapy after a bisphosphonate, unless otherwise indicated, in order to reduce the loss of bone mineral density (BMD) after its discontinuation and also to support treatment to reduce bone turnover biomarkers as much as possible after stopping denosumab.
“We saw in our study that, even if you give bisphosphonates after denosumab discontinuation, [patients] could lose bone, and the group that controlled the loss of bone had very high control of bone turnover markers,” study author and presenter Bérengère Rozier Aubry, MD, said in an interview at the European Congress of Rheumatology.
She and her colleagues at the Center of Bone Diseases at Lausanne (Switzerland) University Hospital are conducting the ReoLaus (Rebound Effect Observatory in Lausanne) Bone Project to determine whether giving a bisphosphonate to postmenopausal women with osteoporosis after they have discontinued denosumab can stop the loss of bone mineral density (BMD) observed in many patients up to 2 years after stopping denosumab. This postdenosumab BMD loss has also been observed to occur with multiple spontaneous vertebral fractures.
Nearly half of patients who start denosumab discontinue it within 1 year, and 64% by 2 years, according to U.S. administrative claims data (Osteoporos Int. 2017 Apr. doi: 10.1007/s00198-016-3886-y), even though it can be taken for up to 10 years. The discontinuation is either because the patient wishes to do so or there’s a medical indication such as stopping aromatase inhibitor treatment, resolution of osteoporosis, or side effects, Dr. Rozier Aubry said in a press conference at the European Congress of Rheumatology.
Upon discontinuing denosumab, there’s a marked rebound effect in which levels of bone turnover markers rise for 2 years, and some or all of the BMD that was gained is lost (J Clin Endocrinol Metab. 2011 Apr. doi: 10.1210/jc.2010-1502). Multiple spontaneous vertebral fractures also have been reported in 5%-7%, as Dr. Rozier Aubry and colleagues first described in 2016 (Osteoporos Int. 2016 May. doi: 10.1007/s00198-015-3380-y) and others have reported subsequently.
Recommendations from the Endocrine Society in March 2019, a 2017 position statement from the European Calcified Tissue Society, and guidelines from other groups advise giving antiresorptive treatment (bisphosphonates, hormone therapy, or selective estrogen-receptor modulators) but do not say which one, in what dose, when, or for how long, Dr. Rozier Aubry noted.
Treatment with zoledronate 6 months after the last denosumab injection achieves partial preservation of BMD, but multiple vertebral fractures have still been reported when raloxifene, ibandronate, or alendronate have been given after stopping denosumab, she said.
In the ReoLaus Bone Project, Dr. Rozier Aubry and associates are following 170 postmenopausal women with osteoporosis at Lausanne University Hospital who are taking denosumab therapy. At the congress, she reported on the first 71 women in the cohort with 1 year of follow-up. They had a mean age of 64 years, had fewer than one prevalent fracture before starting denosumab, and stopped denosumab after a mean of 7.7 injections. Overall, 8% took glucocorticoids, and 22% took aromatase inhibitors.
The investigators collected data on what treatment was used after denosumab, how bone turnover markers changed 1-3 months after the last denosumab injection and then regularly afterward, how bone mineral density changed after 1 year, and any new osteoporotic fractures.
At the time of denosumab discontinuation, 59% received zoledronate, 24% alendronate, 3% other drugs, and 14% nothing. At a mean of about 17 months after the last denosumab injection, the investigators classified 30 patients as BMD losers (losing at least 3.96%), and 41 had stable BMD. The researchers found that BMD losers were younger (61.4 years vs. 65.5 years), were less likely to use zoledronate before starting denosumab (0% vs. 12%), and had greater serum CTX (C-telopeptide cross-linked type 1 collagen) levels at denosumab initiation (644 ng/mL vs. 474 ng/mL) and 12.8 months after stopping denosumab (592 ng/mL vs. 336 ng/mL) than did those with stable BMD. All differences were statistically significant.
“Our results support the use of denosumab in second line after bisphosphonate therapy to restrain the BMD loss at its discontinuation ... and a strategy to maintain the bone turnover marker serum CTX as low as possible after denosumab discontinuation,” she concluded.
“Our proposition is to start with 1 or 2 years of bisphosphonates, and if the osteoporosis is severe, to switch to denosumab treatment for 4, 6 years. … We can use denosumab for 10 years without side effects, and after that we give bisphosphonates to consolidate the treatment,” she said.
Dr. Rozier Aubry and her associates plan to follow patients in their study for 2 years.
Dr. Rozier Aubry disclosed serving on speakers bureaus for Eli Lilly, Pfizer, Amgen, and Novartis.
SOURCE: Rozier Aubry B et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):115; Abstract OP0085. doi: 10.1136/annrheumdis-2019-eular.4175.
REPORTING FROM EULAR 2019 CONGRESS
Mycophenolate, cyclophosphamide found equal as induction therapy in pediatric lupus nephritis
according to findings in the real-world U.K. Juvenile Systemic Lupus Erythematosus Cohort Study.
The study involved 34 patients who received mycophenolate mofetil and 17 who received IV cyclophosphamide as induction therapy for proliferative lupus nephritis in juvenile-onset systemic lupus erythematosus (JSLE). Along with her coinvestigators, first author Eve M.D. Smith, MD, PhD, of the University of Liverpool (England) and Alder Hey Children’s NHS Foundation Trust, described it as the largest study to date investigating induction treatments for proliferative lupus nephritis in JSLE.
The patients were aged 16 years or younger at diagnosis and monitored during 2006-2018 as part of the U.K. JSLE Cohort Study. They met four or more American College of Rheumatology SLE classification criteria and had a renal biopsy result demonstrating proliferative lupus nephritis, defined as class III or IV lupus nephritis by the International Society of Nephrology/Renal Pathology Society. Within the mycophenolate group, half received oral prednisolone only and half received both IV methylprednisolone and oral prednisolone, whereas 2 in the cyclophosphamide group received oral prednisolone only and 15 received both IV methylprednisolone and oral prednisolone.
All the patient demographic factors at baseline – including gender, ethnicity, age at diagnosis, and age at lupus nephritis onset – were similar in both treatment groups.
The investigators detected no significant differences between the two treatment groups at 4-8 and 10-14 months post renal biopsy and last follow-up in renal pediatric British Isles Lupus Assessment Grade scores, urine albumin/creatinine ratio, serum creatinine, erythrocyte sedimentation rate, anti-double stranded DNA antibody, Complement 3 levels, and patient/physician global scores. JSLE-related damage on the Systemic Lupus International Collaborating Clinics Standardized Damage Index also was no different between the groups after a median 13 months following renal biopsy. Lupus nephritis became inactive in 82%-85% of each group, taking a median of 262 days with mycophenolate and 151 days with IV cyclophosphamide, while flares occurred in 69% treated with mycophenolate at a median of 451 days and in 50% with cyclophosphamide at a median of 343 days.
“Results from the presented study highlight the need for prospective comparison of mycophenolate mofetil versus IV cyclophosphamide induction treatment to better inform lupus nephritis treatment protocols for children, especially given IV cyclophosphamide’s poor safety profile,” the investigators wrote.
SOURCE: Smith EMD et al. Lupus. 2019 Mar 14. doi: 10.1177/0961203319836712.
according to findings in the real-world U.K. Juvenile Systemic Lupus Erythematosus Cohort Study.
The study involved 34 patients who received mycophenolate mofetil and 17 who received IV cyclophosphamide as induction therapy for proliferative lupus nephritis in juvenile-onset systemic lupus erythematosus (JSLE). Along with her coinvestigators, first author Eve M.D. Smith, MD, PhD, of the University of Liverpool (England) and Alder Hey Children’s NHS Foundation Trust, described it as the largest study to date investigating induction treatments for proliferative lupus nephritis in JSLE.
The patients were aged 16 years or younger at diagnosis and monitored during 2006-2018 as part of the U.K. JSLE Cohort Study. They met four or more American College of Rheumatology SLE classification criteria and had a renal biopsy result demonstrating proliferative lupus nephritis, defined as class III or IV lupus nephritis by the International Society of Nephrology/Renal Pathology Society. Within the mycophenolate group, half received oral prednisolone only and half received both IV methylprednisolone and oral prednisolone, whereas 2 in the cyclophosphamide group received oral prednisolone only and 15 received both IV methylprednisolone and oral prednisolone.
All the patient demographic factors at baseline – including gender, ethnicity, age at diagnosis, and age at lupus nephritis onset – were similar in both treatment groups.
The investigators detected no significant differences between the two treatment groups at 4-8 and 10-14 months post renal biopsy and last follow-up in renal pediatric British Isles Lupus Assessment Grade scores, urine albumin/creatinine ratio, serum creatinine, erythrocyte sedimentation rate, anti-double stranded DNA antibody, Complement 3 levels, and patient/physician global scores. JSLE-related damage on the Systemic Lupus International Collaborating Clinics Standardized Damage Index also was no different between the groups after a median 13 months following renal biopsy. Lupus nephritis became inactive in 82%-85% of each group, taking a median of 262 days with mycophenolate and 151 days with IV cyclophosphamide, while flares occurred in 69% treated with mycophenolate at a median of 451 days and in 50% with cyclophosphamide at a median of 343 days.
“Results from the presented study highlight the need for prospective comparison of mycophenolate mofetil versus IV cyclophosphamide induction treatment to better inform lupus nephritis treatment protocols for children, especially given IV cyclophosphamide’s poor safety profile,” the investigators wrote.
SOURCE: Smith EMD et al. Lupus. 2019 Mar 14. doi: 10.1177/0961203319836712.
according to findings in the real-world U.K. Juvenile Systemic Lupus Erythematosus Cohort Study.
The study involved 34 patients who received mycophenolate mofetil and 17 who received IV cyclophosphamide as induction therapy for proliferative lupus nephritis in juvenile-onset systemic lupus erythematosus (JSLE). Along with her coinvestigators, first author Eve M.D. Smith, MD, PhD, of the University of Liverpool (England) and Alder Hey Children’s NHS Foundation Trust, described it as the largest study to date investigating induction treatments for proliferative lupus nephritis in JSLE.
The patients were aged 16 years or younger at diagnosis and monitored during 2006-2018 as part of the U.K. JSLE Cohort Study. They met four or more American College of Rheumatology SLE classification criteria and had a renal biopsy result demonstrating proliferative lupus nephritis, defined as class III or IV lupus nephritis by the International Society of Nephrology/Renal Pathology Society. Within the mycophenolate group, half received oral prednisolone only and half received both IV methylprednisolone and oral prednisolone, whereas 2 in the cyclophosphamide group received oral prednisolone only and 15 received both IV methylprednisolone and oral prednisolone.
All the patient demographic factors at baseline – including gender, ethnicity, age at diagnosis, and age at lupus nephritis onset – were similar in both treatment groups.
The investigators detected no significant differences between the two treatment groups at 4-8 and 10-14 months post renal biopsy and last follow-up in renal pediatric British Isles Lupus Assessment Grade scores, urine albumin/creatinine ratio, serum creatinine, erythrocyte sedimentation rate, anti-double stranded DNA antibody, Complement 3 levels, and patient/physician global scores. JSLE-related damage on the Systemic Lupus International Collaborating Clinics Standardized Damage Index also was no different between the groups after a median 13 months following renal biopsy. Lupus nephritis became inactive in 82%-85% of each group, taking a median of 262 days with mycophenolate and 151 days with IV cyclophosphamide, while flares occurred in 69% treated with mycophenolate at a median of 451 days and in 50% with cyclophosphamide at a median of 343 days.
“Results from the presented study highlight the need for prospective comparison of mycophenolate mofetil versus IV cyclophosphamide induction treatment to better inform lupus nephritis treatment protocols for children, especially given IV cyclophosphamide’s poor safety profile,” the investigators wrote.
SOURCE: Smith EMD et al. Lupus. 2019 Mar 14. doi: 10.1177/0961203319836712.
FROM LUPUS
Cimzia becomes first FDA-approved treatment for nonradiographic axial spondyloarthritis
, with objective evidence of inflammation, making it the first treatment approved by the agency for the condition.
The FDA approved the tumor necrosis factor inhibitor based on results from a randomized clinical trial in 317 adult patients with nonradiographic axial spondyloarthritis (nr-axSpA) who had elevated C-reactive protein levels and/or sacroiliitis (inflammation of the sacroiliac joints) on MRI.
The trial entailed 52 weeks of double-blind therapy with certolizumab at a starting dose of 400 mg on weeks 0, 2, and 4 followed by 200 mg every 2 weeks, or placebo. The Ankylosing Spondylitis Disease Activity Score Major Improvement rate, defined as at least a 2-point improvement from baseline, was 47% in the active treatment arm, compared with 7% on placebo. The Assessment in Ankylosing Spondylitis International Society 40% response rate, a more patient-reported outcome measure, was 57% in the certolizumab group and 16% in controls (Arthritis Rheumatol. 2019 March 8. doi: 10.1002/art.40866).
The overall safety profile observed in the Cimzia treatment group was consistent with the known safety profile of certolizumab.
Cimzia was first approved in 2008 and has FDA-approved indications for adult patients with Crohn’s disease, moderate to severe rheumatoid arthritis, active ankylosing spondylitis and moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
, with objective evidence of inflammation, making it the first treatment approved by the agency for the condition.
The FDA approved the tumor necrosis factor inhibitor based on results from a randomized clinical trial in 317 adult patients with nonradiographic axial spondyloarthritis (nr-axSpA) who had elevated C-reactive protein levels and/or sacroiliitis (inflammation of the sacroiliac joints) on MRI.
The trial entailed 52 weeks of double-blind therapy with certolizumab at a starting dose of 400 mg on weeks 0, 2, and 4 followed by 200 mg every 2 weeks, or placebo. The Ankylosing Spondylitis Disease Activity Score Major Improvement rate, defined as at least a 2-point improvement from baseline, was 47% in the active treatment arm, compared with 7% on placebo. The Assessment in Ankylosing Spondylitis International Society 40% response rate, a more patient-reported outcome measure, was 57% in the certolizumab group and 16% in controls (Arthritis Rheumatol. 2019 March 8. doi: 10.1002/art.40866).
The overall safety profile observed in the Cimzia treatment group was consistent with the known safety profile of certolizumab.
Cimzia was first approved in 2008 and has FDA-approved indications for adult patients with Crohn’s disease, moderate to severe rheumatoid arthritis, active ankylosing spondylitis and moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
, with objective evidence of inflammation, making it the first treatment approved by the agency for the condition.
The FDA approved the tumor necrosis factor inhibitor based on results from a randomized clinical trial in 317 adult patients with nonradiographic axial spondyloarthritis (nr-axSpA) who had elevated C-reactive protein levels and/or sacroiliitis (inflammation of the sacroiliac joints) on MRI.
The trial entailed 52 weeks of double-blind therapy with certolizumab at a starting dose of 400 mg on weeks 0, 2, and 4 followed by 200 mg every 2 weeks, or placebo. The Ankylosing Spondylitis Disease Activity Score Major Improvement rate, defined as at least a 2-point improvement from baseline, was 47% in the active treatment arm, compared with 7% on placebo. The Assessment in Ankylosing Spondylitis International Society 40% response rate, a more patient-reported outcome measure, was 57% in the certolizumab group and 16% in controls (Arthritis Rheumatol. 2019 March 8. doi: 10.1002/art.40866).
The overall safety profile observed in the Cimzia treatment group was consistent with the known safety profile of certolizumab.
Cimzia was first approved in 2008 and has FDA-approved indications for adult patients with Crohn’s disease, moderate to severe rheumatoid arthritis, active ankylosing spondylitis and moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
Resistant hypertension hits SLE patients hard
at a tertiary care center.
A patient with resistant hypertension either has blood pressure remaining above 140/90 mm Hg while taking three antihypertensive medications or requires the use of four or more antihypertensives to attain blood pressure control. Resistant hypertension, which was more likely to occur among blacks and patients with lower renal function, hypercholesterolemia, and increased inflammatory markers, increased the risk of death nearly threefold (hazard ratio, 2.91; P = .0005) when compared with those who didn’t have this condition.
The results of this analysis were published March 15 in Arthritis Care & Research (doi: 10.1002/acr.23880). We covered this study at the 2018 annual meeting of the American College of Rheumatology in Chicago before it was published in the journal. Read our previous story at the link above.
at a tertiary care center.
A patient with resistant hypertension either has blood pressure remaining above 140/90 mm Hg while taking three antihypertensive medications or requires the use of four or more antihypertensives to attain blood pressure control. Resistant hypertension, which was more likely to occur among blacks and patients with lower renal function, hypercholesterolemia, and increased inflammatory markers, increased the risk of death nearly threefold (hazard ratio, 2.91; P = .0005) when compared with those who didn’t have this condition.
The results of this analysis were published March 15 in Arthritis Care & Research (doi: 10.1002/acr.23880). We covered this study at the 2018 annual meeting of the American College of Rheumatology in Chicago before it was published in the journal. Read our previous story at the link above.
at a tertiary care center.
A patient with resistant hypertension either has blood pressure remaining above 140/90 mm Hg while taking three antihypertensive medications or requires the use of four or more antihypertensives to attain blood pressure control. Resistant hypertension, which was more likely to occur among blacks and patients with lower renal function, hypercholesterolemia, and increased inflammatory markers, increased the risk of death nearly threefold (hazard ratio, 2.91; P = .0005) when compared with those who didn’t have this condition.
The results of this analysis were published March 15 in Arthritis Care & Research (doi: 10.1002/acr.23880). We covered this study at the 2018 annual meeting of the American College of Rheumatology in Chicago before it was published in the journal. Read our previous story at the link above.
FROM ARTHRITIS CARE & RESEARCH
Belimumab data out to 13 years show continued safety, efficacy
New data from the longest continuous belimumab treatment in a clinical trial of patients with systemic lupus erythematosus (SLE) indicate similar or lower adverse events each year and maintenance of efficacy for up to 13 years in those who initially respond to and stay on treatment.
First author Daniel J. Wallace, MD, and his colleagues reported in Arthritis & Rheumatology on 298 patients who continued from a phase 2 trial of 476 patients and its extension phase to a continuation study with belimumab (Benlysta) plus standard of care. These patients entered the continuation study having gone from placebo to 10 mg/kg belimumab or continued on 1, 4, or 10 mg/kg belimumab or escalated treatment up to 10 mg/kg. They needed to have an improvement in Physician’s Global Assessment (PGA) score, compared with baseline, and had no severe flare in the last 30 days of the extension study.
At year 5, 70% of patients were still in the study, and this declined to 44% at year 10 and 32% (96 patients) at the end of the study. There were stable or declining rates of the most common adverse events from year 1 to year 11 or later, and serious infections and infestations occurred at a stable rate, from 3.7 per 100 patient-years in year 1 to 6.7 per 100 patients-years through year 11, despite a reduction in immunoglobulin G levels during the study. A total of 15% of patients overall withdrew because of adverse events.
The overall SLE Responder Index response rate rose as the number of participants declined, going from 33% at 1 year and 16 weeks to 76% at 12 years and 32 weeks.
In addition to consistently low flare rates starting at year 5, “those patients remaining had reduced requirements for corticosteroids, and the percentage achieving low disease activity increased. Furthermore, patients continued to have serological improvements. ” Dr. Wallace and his coauthors wrote.
“Patients who remained in the study were likely to be those who responded better or tolerated belimumab better than patients who withdrew; hence, the findings may not be representative of all patients with SLE,” they said.
GlaxoSmithKline and Human Genome Sciences funded the study. Most of the investigators received grants, research support, or consulting fees; held shares in; or were employees of GlaxoSmithKline.
New data from the longest continuous belimumab treatment in a clinical trial of patients with systemic lupus erythematosus (SLE) indicate similar or lower adverse events each year and maintenance of efficacy for up to 13 years in those who initially respond to and stay on treatment.
First author Daniel J. Wallace, MD, and his colleagues reported in Arthritis & Rheumatology on 298 patients who continued from a phase 2 trial of 476 patients and its extension phase to a continuation study with belimumab (Benlysta) plus standard of care. These patients entered the continuation study having gone from placebo to 10 mg/kg belimumab or continued on 1, 4, or 10 mg/kg belimumab or escalated treatment up to 10 mg/kg. They needed to have an improvement in Physician’s Global Assessment (PGA) score, compared with baseline, and had no severe flare in the last 30 days of the extension study.
At year 5, 70% of patients were still in the study, and this declined to 44% at year 10 and 32% (96 patients) at the end of the study. There were stable or declining rates of the most common adverse events from year 1 to year 11 or later, and serious infections and infestations occurred at a stable rate, from 3.7 per 100 patient-years in year 1 to 6.7 per 100 patients-years through year 11, despite a reduction in immunoglobulin G levels during the study. A total of 15% of patients overall withdrew because of adverse events.
The overall SLE Responder Index response rate rose as the number of participants declined, going from 33% at 1 year and 16 weeks to 76% at 12 years and 32 weeks.
In addition to consistently low flare rates starting at year 5, “those patients remaining had reduced requirements for corticosteroids, and the percentage achieving low disease activity increased. Furthermore, patients continued to have serological improvements. ” Dr. Wallace and his coauthors wrote.
“Patients who remained in the study were likely to be those who responded better or tolerated belimumab better than patients who withdrew; hence, the findings may not be representative of all patients with SLE,” they said.
GlaxoSmithKline and Human Genome Sciences funded the study. Most of the investigators received grants, research support, or consulting fees; held shares in; or were employees of GlaxoSmithKline.
New data from the longest continuous belimumab treatment in a clinical trial of patients with systemic lupus erythematosus (SLE) indicate similar or lower adverse events each year and maintenance of efficacy for up to 13 years in those who initially respond to and stay on treatment.
First author Daniel J. Wallace, MD, and his colleagues reported in Arthritis & Rheumatology on 298 patients who continued from a phase 2 trial of 476 patients and its extension phase to a continuation study with belimumab (Benlysta) plus standard of care. These patients entered the continuation study having gone from placebo to 10 mg/kg belimumab or continued on 1, 4, or 10 mg/kg belimumab or escalated treatment up to 10 mg/kg. They needed to have an improvement in Physician’s Global Assessment (PGA) score, compared with baseline, and had no severe flare in the last 30 days of the extension study.
At year 5, 70% of patients were still in the study, and this declined to 44% at year 10 and 32% (96 patients) at the end of the study. There were stable or declining rates of the most common adverse events from year 1 to year 11 or later, and serious infections and infestations occurred at a stable rate, from 3.7 per 100 patient-years in year 1 to 6.7 per 100 patients-years through year 11, despite a reduction in immunoglobulin G levels during the study. A total of 15% of patients overall withdrew because of adverse events.
The overall SLE Responder Index response rate rose as the number of participants declined, going from 33% at 1 year and 16 weeks to 76% at 12 years and 32 weeks.
In addition to consistently low flare rates starting at year 5, “those patients remaining had reduced requirements for corticosteroids, and the percentage achieving low disease activity increased. Furthermore, patients continued to have serological improvements. ” Dr. Wallace and his coauthors wrote.
“Patients who remained in the study were likely to be those who responded better or tolerated belimumab better than patients who withdrew; hence, the findings may not be representative of all patients with SLE,” they said.
GlaxoSmithKline and Human Genome Sciences funded the study. Most of the investigators received grants, research support, or consulting fees; held shares in; or were employees of GlaxoSmithKline.
FROM ARTHRITIS & RHEUMATOLOGY