Efficacy and Safety of Rituximab in Systemic Lupus Erythematosus and Sjögren Syndrome Patients With Refractory Thrombocytopenia: A Retrospective Study of 21 Cases

Abstract

Objective: Recent studies suggested a potential of rituximab (RTX) in treating autoimmune thrombocytopenia (AITP) secondary to autoimmune diseases. In this study, we retrospectively evaluated the efficacy and safety of RTX therapy in patients with refractory AITP secondary to systemic lupus erythematosus (SLE) and Sjögren syndrome (SS).

Methods: Twenty-one SLE and/or SS patients with treatment-resistant AITP were treated once or repeatedly with RTX at the Rheumatology Clinic Renji Hospital, during the period March 2012 to June 2014. Clinical and laboratory variables recorded at every follow-up visit were analyzed.

Results: The median age of all patients was 37.05 ± 3.15 years (range, 13-67 years; 20 female and 1 male). The median AITP duration before RTX treatment was 5.46 years. Previous treatments of 21 patients included immunosuppressive agents such as corticosteroids (n = 19), cyclosporine (n = 9), mycophenolate mofetil (n = 2), methotrexate (n = 3), cyclophosphamide (n = 2), vincristine (n = 3), and hydroxychloroquine (n = 15), and 7 patients received concomitantly intravenous immunoglobulin therapy. Two patients had undergone splenectomy without improvement. Seventeen patients (80.95%) were treated repeatedly with RTX during the follow-up period. The overall response rate to RTX treatment (including complete response, 52.38%; partial response, 28.57%) was 80.95%. A significant increase (P < 0.05) of platelet counts was seen after 1 month (median, 32.24 × 10/mL vs 66.53 × 10/mL). Relapses occurred mostly during the first 9 months, and maintaining duration of response was 10.27 months (range, 2-17 months) on average after the first RTX infusion. Antiplatelet antibodies, especially IgG isotype, decreased significantly (P < 0.05) after RTX treatment. No adverse effects were observed among 15 patients (71.4%); however, 2 cases died of severe pneumonia, and another developed lymphoma.

Conclusions: Rituximab is an additional potent therapeutic treatment option for SLE and SS patients with AITP refractory to conventional immunosuppressive treatments. For most patients, RTX was safe and well tolerated.

FIGURE 1

Platelet count response before and after RTX treatment. A, Box plots show the 25th and 75th percentiles. Horizontal black solid lines within boxes indicate medians; filled circles indicate means. Vertical bars indicate the fifth and 95th percentiles. *P < 0.05 as compared with levels before treatment. B, The overall response during follow-up. Each column represents response rate at a particular time point. NR indicates NR.

FIGURE 2

Monitoring of laboratory parameters before and after RTX treatment. A, B-cell repopulation 1 month after RTX infusion. Each dot represents CD19⁺ B cells percentage. Each dot represents response of single patient. Normal values are as follows: CD19⁺ B cells, 180–350 × 10⁶/L. B, Changes in APAs following RTX treatment. Box plots show the 25th and 75th percentiles. Horizontal black solid lines within boxes indicate medians. Vertical bars indicate the fifth and 95th percentiles. Normal values are as follows: IgG antibodies: 0 to 120 ng/10⁷ PA, IgM antibodies: 0 to 40 ng/10⁷ PA, IgA antibodies: 0 to 22 ng/10⁷ PA. C and D, Changes in anti-dsDNA antibodies and complements (C3, C4) following RTX treatment. Normal values are as follows: anti-dsDNA antibodies, 0 to 7 IU/mL; C3, 0.9 to 1.8 g/L; C4, 0.1 to 0.4 g/L. E, Changes in SLEDAI scores among 15 SLE patients following RTX treatment.