Clinical Research Of Low Dose Rituximab In ITP Patients With Different Platelet-specific Autoantibodies

Background and ObjectivePrimary immune thrombocytopenia (ITP) is a common acquired immune-mediated bleeding disorders characterized by thrombocytopenia, in which membrane glycoprotein(GP)-specific autoantibodies sensitize the platelets or megakaryocytes causing increased destruction and decreased production of platelets. The main target antigens are GPⅡb/Ⅲa and GPⅠb/Ⅸ. Rituximab is an effective treatment by removing B lymphocyte, which may prolong the time intervention before splenectomy for ITP patients failing of corticosteroids therapy. Proper use and individualized choice of rituximab are the critical points in ITP treatment. While there is no indication to predict which patients may be effective to rituximab treatment. The objective of this study was to analyze the relationship between the anti-GPⅡb/Ⅲa or GPⅠb/Ⅸ antibodies and the efficacy of low dose rituximab (LD-RTX) in ITP patients failing of corticosteroids therapy. We tried to find the factors influencing the efficacy of LD-RTX and formulate an effective second-line treatment in ITP patients.MethodsWe enrolled ITP patients failing of corticosteroids therapy (invalid, tolerant or relapsing) who underwent low dose rituximab (100mg/w ×4 weeks) treatment. Meanwhile we used a monoclonal antibody-specific immobilization of platelet antigens (MAIPA) test to detect platelet GPⅡb/Ⅲa and GPⅠb/Ⅸ-specific autoantibodies. We recorded patients’ general cases (age, gender, bleeding symptoms and initial platelet counts) and then observed the platelet counts and side effects after LD-RTX treatment. The response outcome was defined as platelet counts>30×109/L and a doubling of baseline counts, and an absence of bleeding. Then we analyzed the diversity of LD-RTX efficacy in primary ITP patients with different anti-GP antibodies.ResultsWe assessed fifty-eight ITP patients failing of corticosteroids therapy with complete low-dose rituximab treatment and follow-up observation. The median age was 39 years old and the ratio of male to female was 25/33.(1) The rate of anti-GP antibodies was 70.7% (41/58) in which the anti-GPⅡb/Ⅲa and anti-GPⅠb/Ⅸ antibody positive rate respectively were 51.7% (30/58) and 48.3% (28/58), and the double-positive rate was 29.3%(17/58). The double-negative rate was also 29.3% (17/58).(2) The initial response rate to LD-RTX was 60.3% (35/58) with a median onset time of 37.5 days and a duration time up to 15.5 months, in which the complete response rate was 39.7% (23/58).(3) Our study showed that patients with anti-GPⅡb/Ⅲa antibody were more sensitive to LD-RTX treatment (73.3% vs 46.4%, P< 0.05) than without anti-GPⅡb/Ⅲa antibody, while the onset time and duration time did not significantly differ between groups (P> 0.05). There was no significant difference in efficacy, the onset time and duration time between anti-GPⅠb/Ⅸ antibody positive and negative patients (P> 0.05). The patients’ age, sex, bleeding symptoms and pretreatment platelet counts were not associated with the response of LD-RTX treatment (P> 0.05) In addition, there was no interaction between the two autoantibody types (P> 0.05, OR 2.700,95% CI 0.841-8.668).(4) In this research, one patient dropped out due to drug-related adverse reactions. All 58 eligible patients were well tolerated to LD-RTX treatment and the adverse reactions experienced were mild including fatigue, edema, nausea, anorexia, slight lung infections and infusion reactions.Conclusions1. Most of the primary ITP patients failing of corticosteroids therapy express platelet membrane GP-specific antibodies in which the major target antigens are GPⅡb/Ⅲa and GPⅠb/Ⅸ.2. LD-RTX treatment yields dramatical and long-term efficacy in ITP patients failing of corticosteroids therapy.3. In the ITP patients failing of corticosteroids therapy, anti-GPⅡb/Ⅲa autoantibody positive patients are more sensitive to LD-RTX treatment. Thus, anti-GPⅡb/Ⅲa autoantibody may predict an effective LD-RTX therapy, while anti-GPIb/IX autoantibody may not.