Rituximab for the Treatment of Refractory Inflammatory Myopathies and Refractory Myasthenia Gravis
Condition: Myositis; Myasthenia Gravis
MeSH terms: Myasthenia Gravis; Muscle Weakness; Myositis
Study type: Interventional
Phase: Phase 2

Summary: 
      The traditional treatment of inflammatory myopathies (IM) and generalized myasthenia gravis
      (MG) is immunosuppressive therapy, usually beginning with corticosteroids. However, up to 70%
      of treated patients show an incomplete response, including 10 - 30% who are unresponsive.
      Corticosteroids and other immunosuppressive therapies presented also many side effects. We
      propose to evaluate in a pilot, open, prospective, multicentric, phase II study, the interest
      of rituximab in the treatment of patients with primary IM associated with specific AAb
      (anti-synthetase and anti-SRP AAbs), or MG (with anti-AchR AAbs), refractory to conventional
      therapies. Twenty fourth patients with primary IM (12 with anti-synthetase, 12 with anti-SRP
      AAbs), and 12 with MG will be included in the study.
    

Detailed description: 
      Rituximab, a chimeric monoclonal antibody specific for human CD20, which targets B
      lymphocytes, has been first developed as biotherapy for the treatment of B lymphoma. In this
      context, hundred thousands patients received this drug, with a very good tolerance. Recently,
      interest has grown in the pivotal role of B cells for auto-immune humorally mediated
      diseases. Rituximab could then be a potential new biological treatment for such diseases,
      especially for patients refractory to conventional therapies. As a Muscular Diseases Centre,
      we have a large recruitment of patients with inflammatory myopathies (IM) and myasthenia
      gravis (MG). Although the physiopathogenesis of these two conditions differ, both can be
      associated with specific auto-antibodies (AAbs) and their therapeutic management is almost
      similar. The traditional treatment approach to IM and generalized MG is immunosuppressive
      therapy, usually beginning with corticosteroids. However, up to 70% of treated patients show
      an incomplete response, including 10 - 30% who are unresponsive. We propose to evaluate in a
      pilot, open, prospective, multicentric, phase II study, the interest of rituximab in the
      treatment of patients with primary IM associated with specific AAb (anti-synthetase and
      anti-SRP AAbs), or MG (with anti-AchR AAbs), refractory to conventional therapies.

      Inclusions criteria are IM (as defined by the 119th European Neuromuscular Centre workshop)
      or generalised MG (as defined by the Texas Clinical Classification System) associated with
      specific AAbs (anti-synthetases (JO1, PL7 or PL12), or anti-SRP for primary IM, and anti-AchR
      for MG) and refractory to conventional treatments defined as an inadequate response to, or
      intolerable side effects with conventional treatments, such as corticosteroids, azathioprine,
      methotrexate, cyclophosphamide, cyclosporine, IgIV and/or plasma exchange.

      The therapeutical schema is rituximab 1000 mg, 2 times (at day 0 and 15), followed by one
      single injection (1000 mg) 6 months latter and end of follow up at 1 year.

      The efficacy is evaluated by an improvement of Kendall's muscular testing or MG muscular
      score at month 12. Secondary criteria include Kendall's muscular testing or MG muscular score
      at day 21 and month 7, quality of life auto-questionnaire (SF 36), evolution of CK levels and
      AAb titers.

      Twenty fourth patients with primary IM (12 with anti-synthetase, 12 with anti-SRP AAbs), and
      12 with MG will be included in the study. If a success is observed in at least 6 patients, it
      will be possible to conclude that the response rate is above 25% (lower 90% confidence
      interval for observed response rate 50%).
    

Intervention name(s): Rituximab
Intervention type(s): Drug
Intervention description(s): Rituximab 1000 mg intravenous, 2 times, 2 weeks apart and 1000 mg 6 months after the last injection
Intervention MeSH terms: Rituximab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Myositis; Anti-synthetase; Anti-SRP; Myasthenia gravis; Rituximab