Efficacy and Safety of Rituximab in the Treatment of Refractory/Relapsed Idiopathic Thrombocytopenic Purpura (ITP): Results of a Meta-Analysis of 299 Patients.

Background: Rituximab is a chimeric monoclonal antibody (mAb) targeting CD20 antigen on neoplastic and normal B cells. In addition to its role in the treatment CD20-positive B-cell malignancies, rituximab has been approved for symptom management of rheumatoid arthritis. Expanding the use of rituximab in other autoimmune diseases remains investigational. The treatment of auto-antibody mediated platelet destruction in refractory ITP is challenging. Although a good response is seen in the majority of patients treated with steroids and/or splenectomy, relapses occur in half of the patients. A few uncontrolled studies have evaluated the use of rituximab for therapy of relapsed/refractory ITP.

Objective: In order to define the efficacy and safety of rituximab in the treatment of patients with refractory/relapsed ITP we conducted a review of the current available literature and performed a meta-analysis.

Materials and Methods: We conducted a MEDLINE literature search using Pub med, Ovid software for the key words rituximab, ITP and immune thrombocytopenia on all available published literature analyzed to date (Jan 2001 to June 30, 2006). Studies involving children (<18 years) were excluded and our search was limited to reports in English. References of each article were also searched for additional literature. Individual case reports with less than 5 patients were excluded. In addition, studies were analyzed for disease duration, rituximab toxicity, and characteristics of responders.

Results: A total of 34 peer reviewed publications were identified after the electronic search that identified a total of 324 patients. Five abstracts and 14 full-length manuscripts were excluded from the analysis as they included < 5 patients/report. Thus, the meta-analysis consisted of 299 patients described in 15 reports. The mean age of the patients was 50 (39–49 years); about half (52%) had failed splenectomy; mean duration of ITP was 54.4 months. All patients received four weekly doses of rituximab at 375mg/m². The overall response rate was 55%, of which 38% of the patients achieved a complete response (CR) that was defined as a platelet count of at least 100,000–150,000. In addition, 17% of the patients achieved a partial response (PR) (i.e. platelet count >50,000 and < 100,000). The median duration of response in CR patients was 74 weeks (24–120) and in PR patients was 55 weeks (12–160). Of 12 patients re-treated with rituximab: 7 had 2^nd CR (duration 6 m to 4 yrs). CR in splenectomized patients (available from 5 studies, n=126) was higher (62%) than non-splenectomized patients. Initial rise in platelet count in early responders was seen as early as 7–14 days from initiation of therapy.

Discussion: Treatment of relapsed or refractory ITP is based on retrospective studies and no specific guidelines exist. Rituximab-associated depletion of antibody producing B-cells and/or Fc receptor blockade by mAb results in objective responses in over half (55%) of the patients treated. Re-treatment is effective in a similar percentage of patients with durable response. Minimal toxicity with equivalent results to other immunosuppressants favors rituximab’s use in patients with symptomatic refractory ITP. Prospective trials should further validate these results and potentially identify ITP patient characteristics prognostic for responsiveness to rituximab immunotherapy.