Rituximab before splenectomy in adults with primary idiopathic thrombocytopenic purpura: a meta‐analysis

Abstract

SummaryPrimary immune thrombocytopenia (ITP) is an acquired immune-mediated disorder with absence of any underlying cause. Corticosteroids are the standard initial treatment. Splenectomy is the main second-line treatment. A trend to delay or avoid splenectomy has developed thanks to new agents like rituximab. Few studies have assessed the response rate to rituximab in chronic ITP. We performed the first meta-analysis of randomized clinical trials and observational studies on rituximab as an effective splenectomyavoiding option in adult chronic ITP. Overall methods were adapted from published guidelines for meta-analysis (meta-analysis of observational studies in epidemiology and preferred reporting items for systematic reviews and meta-analyses). Two haematologist investigators carried out study selection and data extraction independently, recording overall response rate (ORR) and complete response (CR) as primary assessment criteria. Of 364 records were identified through electronic databases. Of 19 retrospective or prospective observational studies were retained after removing duplicate studies and full-text analyses. The ORR was 57% (95% confidence interval [CI]: 48-65), for 368 non-splenectomized patients after rituximab; CR was 41% (95% CI: 0·33-0·51) for 346 patients. Results were stable for ORR and CR in all sub-analyses. In univariate or multivariate mixed-effect metaregression, age was the most relevant effect. According to our results, rituximab should be used in earlier in non-splenectomized patients.

B cell depletion in immune thrombocytopenia reveals splenic long-lived plasma cells

“…This intense B cell response and considerable expansion of shortlived PB in spleen is thus a hallmark of the disease. Rituximab-induced B cell depletion therapy is widely used in autoimmune diseases, and, accordingly, around 40% of patients with ITP respond to this therapy after 1 year (13) and 20% of them have a long-lasting response (14,15). This rate of response underlines the efficacy of the rituximab treatment, being able to totally block the ongoing production of ASC by proliferating GCs and memory B cells within lymphoid tissues (20).…”

“…Around 40% of patients with ITP have an initial significant response to the anti-CD20 (rituximab) treatment (13) and 20% have a long-lasting (5 years and more) response (14). Among the remaining patients, who do not respond or have a transient response to rituximab, 60%-70% are cured by splenectomy (13)(14)(15). While reports agree on the efficient peripheral B cell depletion achieved by rituximab treatment, much less is known about B cell depletion in lymphoid tissues and the nature of the resistant pathogenic cells.…”

How we manage immune thrombocytopenia in the elderly

“…It has been reported that younger age was associated with better response (Khellaf et al, 2014). A meta-analysis of studies of non-splenectomized patients receiving rituximab confirmed that younger age was the most relevant predictive factor of response in multivariate analysis (Auger et al, 2012). Rituximab may be associated with better response in the early stages of the disease (Khellaf et al, 2014).…”

“…Rituximab in ITP leads to an overall initial response rate of 60%, and 30-40% after 2 years of follow-up (Arnold et al, 2007;Godeau et al, 2008;Auger et al, 2012;Khellaf et al, 2014). It has been reported that younger age was associated with better response (Khellaf et al, 2014).…”

Efficacy and safety of rituximab given at 1,000 mg on days 1 and 15 compared to the standard regimen to treat adult immune thrombocytopenia

“…In France, based on the findings of a single-arm prospective study [4], RTX is now commonly used in persistent or chronic cases of adult ITP prior to splenectomy. Approximately 40-50% of patients treated with RTX at a standard dose achieve a complete response (CR) by 1 year [5] and 20% have a lasting response at 5 years [6]. The mechanisms of action of RTX to treat ITP remain speculative, although the removal of autoreactive B-cells is likely to play an important role.…”