Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: A randomized, placebo‐phase trial

Abstract

Objective To assess the safety and efficacy of rituximab in a randomized, double-blind, placebo-phase, trial of adult and pediatric myositis. Methods Adults with refractory polymyositis and adults and children with refractory dermatomyositis were enrolled. Entry criteria included muscle weakness and ≥2 additional abnormal core set measures (CSM) for adults. JDM patients required ≥ 3 abnormal CSM with or without muscle weakness. Patients were randomized to either ‘rituximab early’ or ‘rituximab late’ and glucocorticoid and immunosuppressive therapy were allowed at entry. The primary endpoint compared the time to achieve the preliminary International Myositis Assessment and Clinical Studies Group definition of improvement (DOI) between the 2 groups. The secondary endpoints were time to achieve ≥20% improvement in muscle strength, and the proportion of early and late rituximab patients achieving DOI at week 8. Results Among 200 randomized patients (76 PM/76 DM/48 JDM), 195 showed no difference in the time to DOI between the rituximab late (n=102) and rituximab early (n=93) groups (p=0.74, log rank) with a median time to DOI of 20.2 weeks and 20.0 weeks respectively. The secondary endpoints also did not significantly differ between the two treatment groups. However, 161 (83%) of randomized patients met the DOI and individual CSM improved in both groups throughout the 44-week trial. Conclusion Although there were no significant differences in the two treatment arms for the primary and secondary endpoints, 83% of refractory adult and juvenile myositis patients met the DOI. The role of B cell depleting therapies in myositis warrants further study with consideration for a different trial design.

Recovery from severe dysphagia in systemic sclerosis - myositis overlap: a case report

“…Patients' refractory to corticosteroids or who require high doses of corticosteroids as maintenance therapy, may respond to immunosuppressive agents such as methotrexate, azathioprine, cyclophosphamide, cyclosporine or mycophenolate mofetil 3 . Intravenous immunoglobulin (IVIG) and rituximab are effective in patients with severe, progressive or refractory inflammatory myopathy [4][5][6][7][8] . Patients with refractory oesophageal involvement require PEG feeding and 82.2% of patients may improve with repeated courses of IVIG…”

The Spectrum of Functional Rating Scales in Neurology Clinical Trials

“…This core set consists of measures in the domains of global activity, muscle strength, physical function, laboratory assessment, and extramuscular disease [22]. This core set measure has been used in clinical trials to enroll patients (inclusion criteria) and for outcomes assessment [23]. The Core Outcome Measures in Effectiveness Trials (COMET) initiative, launched in 2010, brings together researchers interested in the development of core outcome sets (http://www.comet-initiative.org/).…”

Immunotherapies for Neurological Manifestations in the Context of Systemic Autoimmunity

“…First-line treatment includes high-dose oral or IV steroids, followed by steroid-sparing agents such as AZA, MTX, ciclosporin, or mycophenolate mofetil (grade 3C and 3D) [42]. In refractory cases, administration of IVIg or rituximab may be helpful (grade 1A and 1B, respectively) [2,11,42,43]. Ongoing trials are currently evaluating the efficacy of biological agents such as tocilizumab, anakinra, gevokizumab, and alemtuzumab in inflammatory muscle diseases [42], and these agents may as well be tested on patients with an underlying systemic autoimmune disease.…”