Rituximab Induces Long Lasting Clinical and Serological Remission in Refractory Antiphospholipid Syndrome (APS) and Related Disorders.

Abstract INTRODUCTION. Rituximab, a chimeric monoclonal antibody against CD20 expressed on B cells, has been approved for the treatment of B cell neoplasms. Recently, studies have supported the use of rituximab in various autoimmune disorders such as systemic lupus erythematosus (SLE), thrombotic thrombocytopenic purpura (TTP), and idiopathic thrombocytopenic purpura (ITP). We studied its efficacy in the treatment of antiphospholipid syndrome (APS) and APLA-associated TTP and ITP, and measured antiphospholipid antibodies (APLA) and lupus anticoagulant (LA) before and after rituximab therapy. METHOD. The study included 12 patients, 2 with antiphospholipid syndrome (APS) refractory to all known measures, 6 with TTP, and 4 with ITP, all of whom had positive tests for LA and/or APLA. Rituximab was given 375mg/m2 weekly 4 times. We studied clinical remission and duration of remission and the effect of rituximab on APLA and LA. Laboratory investigations included routine blood counts, IgM and IgG APLA to cardiolipin (aCL) and B2GPI, and LA. RESULT. I. Clinical Observation. (a) Two patients (a 29 and 44 year old female) with APS refractory to all measures including glucocorticoids, monthly chemotherapy with IV cyclophosphamide, and plasmapheresis suffered from recurrent thromboses despite anticoagulation with warfarin, and became disabled, spending most of their time in the hospital. Both went into clinical remission following rituximab, resumed full activities, and were able to be weaned off of glucocorticoids and treated with anticoagulation alone. The remissions lasted 15 and 7 months. LA became negative and APLA decreased or became negative in both. (b) Six patients with TTP and positive APLA and/or LA were treated with rituximab in conjunction with exchange plasmapheresis. Five achieved complete remission and one failed. Remissions of TTP lasted 0.5–3 years. (c) Four patients with ITP and positive tests for APLA or LA were treated and 2 went into clinical remission for 0.5 and 2 years, and 2 did not respond. Therapy was well tolerated but one (TTP) developed herpes zoster and another (ITP) had a TIA following remission with rituximab. Laboratory Observation. APLA and LA were studied in selected patients before and after rituximab treatment. LA became negative in 6 out of 8 patients and it remained negative for over 15 months in one patient. Among APLA, IgM B2GPI became negative in 71% (5/7), IgM ACLA became negative in 50% (4/8), IgG APLA, IgG B2GP1 became negative in 50% (2/4) and IgG aCLA became negative in 30% (2/6). In our series, IgM antibodies are more readily decreased by rituximab than IgG antibodies. Decrease in APLA was evident 3–4 months post therapy. SUMMARY. Although rituximab is widely used in autoimmune disorders, it has not been tested in APS. Our data indicate that it is an effective and life saving measure in refractory APS. Rituxan-induced, long lasting clinical remissions along with serological remission are unusual compared to other immunosuppressive therapies. Similar findings were also observed in APLA-associated TTP and ITP. Further prospective study is recommended to evaluate its full potential in APLA-associated disorders.