Rituximab pour les maladies associées aux auto-anticorps anticytokines

Anticytokine autoantibodies are an important and emerging cause of disease. Anticytokine autoantibody-associated diseases include disseminated nontuberculous mycobacterial infection caused by anti-interferon- >= autoantibodies, severe mucocutaneous candidiasis caused by anti-interleukin-17 autoantibodies, and pulmonary alveolar proteinosis caused by anti-granulocyte macrophage colony stimulating factor autoantibodies. Many subjects undergoing treatments related to these diseases fail to respond or develop toxicity to long term therapy. Rituximab, an anti-CD20 monoclonal antibody that targets antibody-producing B cells, has been used successfully to treat autoimmune diseases (e.g., rheumatoid arthritis), as well as syndromes caused by pathogenic anticytokine autoantibodies (e.g., myasthenia gravis and pemphigus vulgaris). This is a phase I, single arm, open-label study evaluating the safety and clinical response to rituximab treatment in subjects (greater than or equal to 18 years of age; n=20) with anticytokine autoantibody-associated diseases who are intolerant or refractory to conventional treatment. Rituximab will be administered as intravenous infusions of 1 gram on days 1 and 15, and subsequently if indicated up to once a month for 5 months (plus or minue 5 days for each visit) starting on approximately day 42. Follow-up visits will occur within 3, 6, 9, 12, 15, and 18 months (plus or minus 2 weeks for each visit) after the last infusion. Subjects will be maintained on a background of appropriate therapy for their respective diseases. The safety and clinical response to rituximab will be assessed by clinical and laboratory parameters while subjects are receiving rituximab, and for an additional year and a half after completion of treatment. Patients may be retreated at the discretion of the Principal Investigator.