Biosimilar of Rituximab for the Treatment of Primary Immune Thrombocytopenic Purpura : A Case-Control Study

INTRODUCTION

Despite their daily use in the treatment of Thrombocytopenic Purpura Immunologic (ITP), rituximab biosimilars have never been evaluated directly in this indication. Our objective was to compare the efficacy and the tolerance of Rixathon ©, systematically used in our structure since April 2018, Mabthera © at adult patients with primary ITP.

PATIENTS AND METHODS

Medical records of the patients treated with Rixathon © for a primary ITP in our structure until December 31, 2019 have been retrospectively analyzed. All of these patients were included in the safety analysis. Patients with ITP secondary to an active malignant hematologic condition, a well-established auto-immune systemic disease or an anti-phospholipid syndrome, as well as patients in whom another ITP treatment was introduced within 8 weeks before or after the first injection of biosimilar, were excluded from the efficacy analysis. Rituximab-naive patients and those who had already received it in the past were separated into two groups. Naive patients were compared with controls from the registry "ITP-Ritux "which contains data from 248 patients treated with Mabthera © for a primary ITP. Rituximab non-naive patients were their own control.

For the efficacy analysis, the primary endpoint used was the initial response to treatment, defined according to international criteria. A complete response corresponded to a platelet count> 100 G / L, a partial response to a level> 30 G / L with a doubling of the platelet count from the level before the injection. All other situations were considered as failures. For the safety analysis, all side effects, whether immediate or delayed, were collected.

RESULTS

A total of 38 patients treated with Rixathon © for ITP were included in the safety analysis. Of these patients, 26 (68%) were rituximab naïve and 6 (16%) had secondary ITP. The majority of patients were women (n = 28, 74%). Most of them were in the chronic stage of ITP (n = 24, 63%). Only 2 (5%) of the patients had undergone splenectomy. The median duration of follow-up was 6 months [IQR 3-12.5 months]. Of the 22 naive patients included in the efficacy study, 7 (32%) had a complete response and 8 (36%) a partial response. The observed overall response rate was 68%, a rate comparable to that observed in the PTI-Ritux registry (61%). In the 10 non-naïve rituximab patients included in the efficacy analysis, 6 (60%) were in complete response and 2 (20%) in partial response, i.e. an overall response rate of 80% in patients who had previously all responded favorably to Mabthera ©. During follow-up, 6 (16%) patients required initiation of at least one other disease-modifying treatment for ITP. Regarding immediate tolerance, 3 (8%) patients had immediate side effects when starting treatment but none required stopping the infusion: one patient presented with hives, another with abdominal pain and finally a patient was hospitalized after the infusion for a flare-up of heart failure. Away from the infusion, transient deep neutropenia was observed in 2 of 12 patients who were not rituximab naive. One of these two patients developed sepsis requiring hospitalization. In addition, during follow-up, one patient presented with pulmonary embolism and another with chronic abdominal pain.

CONCLUSION

The short-term efficacy of Rixathon © appears to overlap with that of Mabthera © in the treatment of primary ITP in adults. Data on a larger scale, with a more prolonged follow-up, are being collected in order to confirm these encouraging data.