Rituxan in polymyositis – pro

Polymyositis and dermatomyositis are inflammatory muscle disorders of unknown etiology currently classified under the rubric of idiopathic inflammatory myopathy (IIM). There are case reports and small proseepctive phase II studies and series.

In an open-label uncontrolled pilot study (n = 7), Levine (2005) reported their findings of 7 adult patients with dermatomyositis (DM), 6 of whom had longstanding illness that was responding inadequately to a number of currently available immunosuppressive agents. All patients received 4 intravenous infusions of rituximab given at weekly intervals. Patients were followed up for up to 1 year without further treatment with rituximab. One patient was lost to follow-up. The principal effectiveness outcome was muscle strength, measured by quantitative dynomometry. All 6 evaluable patients exhibited major clinical improvement, with muscle strength increasing over baseline by 36 to 113 %. Maximal improvements in muscle strength occurred as early as 12 weeks after the initial infusion of rituximab. CD20+ B cells were effectively depleted in all patients by 12 weeks. Four patients experienced a return of symptoms that coincided with the return of B cells before the 52-week end point. Two patients maintained their increased muscle strength at 52 weeks, and 1 of these patients maintained this strength even after the return of B cells. Other symptoms of DM (e.g., rash, alopecia, and reduced forced vital capacity) improved markedly in patients with these symptoms. Rituximab was well-tolerated, with no treatment-related severe or serious adverse events during the observation period of this study. The authors concluded that the results of this small open-label study of DM patients treated with rituximab provided sufficiently encouraging results to justify a more formal evaluation of the value of B cell depletion therapy in the treatment of DM. Furthermore, in a review on “B cell-targeted therapy in diseases other than rheumatoid arthritis”, Looney (2005) stated that “depletion of B cells during rituximab therapy was associated with improvement in global disease activity …. further controlled studies are warranted to optimize rituximab as monotherapy and to develop combination therapies in patients with refractory autoimmune diseases”.

In an open-label study, Mok and colleagues (2007) reported the effectiveness and toxicity of rituximab in the treatment of refractory polymyositis. Adult patients with active polymyositis as evidenced by persistent proximal muscle weakness, elevated creatine kinase (CK) level, and features of active myositis on electromyography who were refractory to corticosteroids and at least 2 other immunosuppressive agents were recruited. While immunosuppressive agents were continued, rituximab (375 mg/m2) was given by intravenous infusion weekly for 4 consecutive weeks. Patients were followed-up 4-weekly for serial assessment of muscle power, serum muscle enzymes, physician’s and patient’s global impression of disease activity, disability, and quality of life scores. Four patients (3 women, 1 man) were studied. The mean age was 53 +/- 11 years and the mean duration of polymyositis was 4.8 +/- 3.3 years. All had persistently active myositis for at least 2 years. At Week 28, significant improvement in the mean proximal muscle power scores and reduction in CK levels in comparison to baseline were observed. Two patients had return of full muscle power with significant drop in CK level. There was a trend of improvement in disability scores as well as both the mental and physical components of the Medical Outcomes Study Short Form-36 Health Survey scores. Rituximab was well-tolerated. The authors concluded that rituximab is an option to be considered in refractory polymyositis, however, further controlled trials are needed to confirm its effectiveness.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the National Institutes of Health is sponsoring the first international multi-center trial to be conducted in both adult and juvenile myositis patients. This multi-center trial (The Rituximab In Myositis (RIM) Study) examines the effectiveness of rituximab, a novel biologic agent. A randomized, double-blind, placebo-phase, multi-centre, phase II trial of intravenous rituximab in the treatment of refractory myositis in adults and children, involving approximately 20 adult centres and 17 paediatric clinical centres in the United States, Canada, United Kingdom, Czech Republic and Sweden will be enrolling a total of 200 participants.

Noss EH, Hausner-Sypek DL, Weinblatt ME. Rituximab as therapy for refractory polymyositis and dermatomyositis. J Rheumatol 2006;33:1021-6.

Levine TD. Rituximab in the treatment of dermatomyositis: an open-label pilot study. Arthritis Rheum 2005;52:601-7.

Mok CC, Ho LY, To CH. Rituximab for refractory polymyositis: An open-label prospective study. J Rheumatol. 2007;34(9):1864-1868.

Chiappetta N, Steier J, Gruber B. Rituximab in the treatment of refractory dermatomyositis. J Clin Rheumatol 2005;11:264-6.

Stringer E, Feldman BM. Advances in the treatment of juvenile dermatomyositis. Curr Opin Rheumatol 2006;18:503-6.

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