Anti B-cell therapy against refractory thrombocytopenia in SLE and MCTD patients: long-term follow-up and review of the literature

Objective The objective of this study was to retrospectively evaluate the clinical and immunological effects of anti-B cell treatment in patients with systemic lupus erythematosus (SLE) and mixed connective-tissue disease (MCTD) with autoimmune thrombocytopenia (AITP) refractory to conventional immunosuppressive treatment. Methods Rituximab (RTX) was added to the ongoing treatment of 16 patients (median age 36 years, range 17-84, all female) with treatment-resistant AITP. Thirteen patients had SLE and three had MCTD. RTX was given intravenously on four occasions during four consecutive weeks at a dose of 375 mg/m(2). Clinical and laboratory disease activity variables recorded at every follow-up visit were analyzed. Results The median disease duration before RTX treatment was nine years (range 0.2-27) and the median post-treatment follow-up time was 28 months (range 3 to 92). Ten patients (63%) were treated repeatedly with RTX during the follow-up period. Complete depletion of B cells was achieved in 94% of cases one month after RTX treatment. A significant increase (p = 0.0001) of platelet counts was seen already after one month (median 58 x 10(9)/ml vs 110 x 10(9)/ml) whereas within three months platelet counts normalized in 10 patients (median 223 x 10(9)/ml). Three patients did not respond to RTX treatment (median platelet count 69 x 10(9)/ml). High titers of anti-platelet antibodies were detected in seven patients before RTX treatment, and the autoantibody titers decreased significantly (p < 0.03) after RTX treatment in six of these patients who also achieved complete remission. A review of the literature revealed 24 articles including 18 case reports, one retrospective cohort study and five prospective studies documenting the outcomes of 65 RTX-treated patients with SLE- or MCTD-related thrombocytopenia with an overall treatment response rate of 80%. In conclusion, these findings indicate that RTX is an additional potent therapeutic treatment option for SLE patients with AITP refractory to conventional immunosuppressive treatment whereas best response may be expected in patients with high titers of anti-platelet antibodies at baseline.