Long‐term outcomes of patients treated with rituximab as second‐line treatment for adult immune thrombocytopenia – Follow‐up of the RITP study

Abstract

Summary RITP was a double‐blind randomized, 78‐week follow‐up trial in which 109 adults with immune thrombocytopenias (ITP) who failed to achieve adequate response to steroids, were randomized to receive rituximab or placebo. Here, we provide the duration of response, splenectomy and mortality rates based on extended follow‐up after completion of the RITP study. Extended follow‐up data were retrospectively collected for 72 (83%) patients out of the 84 patients who were not splenectomized during the initial RITP study. For the present analysis, median [interquartile range] duration of follow‐up after randomization was 72 [62–82] months. Median duration of response among patients who achieved an initial response was significantly longer in patients who received rituximab (8·2 [5·5–16·7] months) as compared to placebo (1·8 [1·3–3·6] months), P = 0·036. Overall, 35 patients underwent splenectomy (13 in the rituximab, and 22 in the placebo arm, P = 0·12). Eleven patients (10%) died during the study: five in the rituximab and six in the placebo arms, including four deaths from severe bleeding. Although most rituximab‐treated patients eventually relapsed, a longer duration of response and a trend towards lower splenectomy rate were observed in rituximab‐treated patients.

Management of Adult Patients with Immune Thrombocytopenia (ITP): A Review on Current Guidance and Experience from Clinical Practice

“…[46][47][48][49] Despite the relapse rate, patients treated with rituximab had a longer duration of response compared with placebo (median 8.2 months vs 1.8 months). 50 Studies examining different dosages of rituximab, including a lower dose of 100 mg/week for four weeks 51 and a dose of 1000 mg on days 1 and 15 did not show significant differences in response rate or infection risks. 52,53 Rituximab has also been studied in combination with other therapies such as high-dose dexamethasone in newly diagnosed ITP, with an initial strong overall response though sustained response after 12 months of follow up decreased to 61.5%, with an 11.1% incidence of adverse effects.…”

High-affinity autoreactive plasma cells disseminate through multiple organs in patients with immune thrombocytopenic purpura

“…In this prototypic antibody-mediated autoimmune disease, B cell depletion using rituximab (anti-CD20 mAb) is widely used, with up to 60% of patients having a short-term complete response ( 15 ), 40% achieving durable responses (6–12 months), and only 20% to 30% achieving a long-term response (5 years; refs. 16 , 17 ). Paradoxically, B cell depletion therapy stimulates an adaptation of splenic short-lived plasma cells that leads to their reprogramming into long-lived spleen cells in patients with ITP, explaining in part primary failure of rituximab ( 13 ).…”

Splenic Artery Embolization in a Patient With Intracranial Hemorrhage Due to Refractory Persistent Immune Thrombocytopenia

“…In a multicenter, double-blind, randomized placebo-controlled trial in un-splenectomized adults with primary IT, rituximab, an anti-CD 20 antibody and off-label drug used to treat IT, did not reduce long-term treatment failure, and infections were significantly higher in the arm administered rituximab 7 . In a follow-up study, the relapse rate was high among rituximab-treated patients 8 . However, in our case, rituximab could not be used before ICH, which occurred in month 6 following the diagnosis.…”