Efficacy of Early Use of Rituximab In Steroid Refractory Severe Immune Thrombocytopenic Purpura In Adult Patients: Single Institution Experience From Saudi Arabia

Immune thrombocytopenic purpura (ITP) is characterized by mucocutaneous purpura and thrombocytopenia. Majority of patients swiftly respond to intravenous immunoglobulin (IVIg) and or steroids therapy but approximately 25% to 30% of adult patients develop a chronic disease that will become refractory to corticosteroids and splenectomy, leading to substantial morbidity and mortality. Guidelines recommend glucocorticoids and splenectomy as standard 1st and 2nd line treatments for chronic ITP but there is considerable variation in 2nd and 3rd line therapies worldwide. In addition to variable response rates immunosuppressive therapies for ITP are associated with substantial side effects, limiting their use for long-term treatment. Management of adults with severe ITP (platelet count less than 10 × 10^9/L) is costly, with IVIg use being a major cost driver. From a budget payer's perspective, the availability of therapeutic agents that could reduce the need for IVIg and emergency hospitalizations could mitigate the costs of current treatments of ITP. Rituximab, a monoclonal antibody to CD-20, has shown promising results in patients with chronic refractory ITP and many patients have this as “off-label” therapy. The rationale for its use in ITP rests on the attempt to eliminate autoreactive B-cell clones. Severe ITP that does not respond to IVIg and steroid therapy is worrisome for both physician and patient due to fears of Intracranial hemorrhage. In this study we evaluated the efficacy of relatively early use of Rituximab for steroid refractory severe ITP.

The data for the reported patients with severe ITP was retrospectively reviewed from medical records. All patients had typical clinical findings of ITP and bone marrow biopsy findings were consistent with peripheral destruction. Six patients who failed to achieve a platelet of > 10 × 10^9/L after IVIG and steroids; or who relapsed after 3 lines of treatment (including IVIG, Prednisone and Dexamathasone pulse) were treated with Rituximab at a dose of 375mg/m^2 weekly for total of four doses (except one patient who underwent splenectomy after 3 doses due to very poor response). Platelet counts were frequently monitored during the follow-up. Complete response (CR) was defined as platelet count >150 × 10^9/L; and partial response (PR) as platelets 50–149×10^9/L. Duration of disease prior to Rituximab and follow up time after Rituximab were recorded.

Median age of patients was 50 years (range 17–59 years). Median duration of ITP prior to Rituximab was 4.5 weeks (range 3–14 weeks). Median of baseline platelet count was 4.5 ×109/L (range 1.2–9 ×109/L) prior to Rituximab. All patients had received 3 lines of prior ITP therapies for at least some time. Severity of thrombocytopenia was the main reason for change to rituximab. Patients had a median follow up of 28 weeks (range 6 to 72 weeks).

No short term (except mild headaches and chills) or long term adverse events were documented among patient who received Rituximab. Complete response was observed in 83.3 % (5/6). This response was sustained without a rescue therapy in all patients except one (80 %). One of the six patients (case #4) who had no response to first 3 doses of rituximab underwent splenectomy (16.6 %). After splenectomy her platelets count remain very low with two episodes of rescue therapy but she reported clinical benefit (no bleeding manifestations) on last follow up.

Although this study is limited by small number but data supports the effectiveness and safety of relatively early use of rituximab in severe steroid refractory ITP patients.

Off Label Use: Rituximab (monoclonal anti-CD20 antibody) has been used in chronic ITP but in USA it is used as off-label drug.