Comparative effectiveness and safety of rituximab and caplacizumab for immuno-mediated Thrombotic Thrombocytopenic Purpura: an overview of systematic reviews.

BACKGROUND

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening disorder caused by anti-ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) antibodies. Although therapeutic plasma exchange (TPE) and corticotherapy have long been the standard of care (SOC), rituximab and caplacizumab are increasingly incorporated into clinical practice. Given that these drugs significantly increase the costs of iTTP treatment, synthesizing the available evidence is important for coverage decisions in resource-limited settings.

OBJECTIVES

To summarize and critically appraise systematic reviews with meta-analyses (SRMAs) evaluating effectiveness and safety of rituximab and caplacizumab for iTTP treatment.

METHODS

PubMed, EMBASE, the Cochrane Library, and LILACS were searched up to August 2025. Two reviewers screened citations, with disagreements resolved by a third reviewer. Data extraction was performed by one reviewer and verified by another. Findings were synthesized narratively.

RESULTS

Seven SRMAs were included: two evaluated rituximab and five caplacizumab. SRMAs of rituximab included non-randomized studies and reported reductions in mortality and relapse when added to SOC, although exacerbation and safety were not assessed. SRMAs of caplacizumab included two randomized and nine non-randomized studies. Mortality reduction with caplacizumab was not demonstrated in randomized trials, although real-world data suggested a survival benefit. Randomized trials showed reduced risk of exacerbation and increased risk of bleeding, but no consistent effect on relapse. All SRMAs were rated as critically low methodological quality.

CONCLUSION

Although SRMAs suggest rituximab and caplacizumab may improve clinical response and survival, with more consistent evidence favoring rituximab, their critically low methodological quality highlights limitations in the current evidence base.