Rituximab for the Treatment of Refractory Inflammatory Myopathies and Refractory Myasthenia Gravis (FORCE)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||FORCE: Rituximab (CD 20+-B Cell-depleting Monoclonal Antibody) for the Treatment of Refractory Inflammatory Myopathies With Specific Antibodies and Refractory Myasthenia Gravis|
- Score of muscular strength (Kendall's muscular testing for myositis or MG muscular score for myasthenia) [ Time Frame: at month 12 ] [ Designated as safety issue: No ]
- - Score of muscular strength (Kendall's muscular testing for myositis or MG muscular score for myasthenia) [ Time Frame: at day 21 and month 12 ] [ Designated as safety issue: No ]
- - Improvement of functional scale score (SF36) [ Time Frame: at day 21 and month 12 ] [ Designated as safety issue: No ]
- - Decrease of CK levels [ Time Frame: at day 21 and month 12 ] [ Designated as safety issue: No ]
- - Evolution of auto-antibody titers [ Time Frame: at day 21 and month 12 ] [ Designated as safety issue: No ]
- - Improvement of extra-muscular activity of the disease such as the level of lung involvement by pulmonary function tests [ Time Frame: at day 21 and month 12 ] [ Designated as safety issue: No ]
- - Improvement in the treatment burden defined as the possibility to decrease the dose or stop some of the drugs used at entry [ Time Frame: at day 21 and month 12 ] [ Designated as safety issue: No ]
|Study Start Date:||January 2008|
|Study Completion Date:||December 2011|
|Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
Rituximab 1000 mg intravenous, 2 times, 2 weeks apart and 1000 mg 6 months after the last injection
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%).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00774462
|Service de Médecine Interne 1 / Groupe Hospitalier Pitié-Salpêtrière|
|Paris, France, 75651 Cedex 13|
|Principal Investigator:||Olivier BENVENISTE, PUPH||Assistance Publique - Hôpitaux de Paris|