# Effectiveness of Rituximab, Belimumab, and Thrombopoietin Receptor Agonists in Refractory Immune Thrombocytopenia Associated With Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis

## TL;DR

This study reviews the effectiveness of three drugs for treating a rare and severe blood disorder in patients with lupus, finding high response rates but noting the need for more research.

## Contribution

The paper provides the first comprehensive meta-analysis of targeted therapies for refractory ITP in SLE patients.

## Key findings

- Rituximab showed an overall response rate of 88.5% in treating refractory ITP in SLE patients.
- Belimumab and TPO-RAs demonstrated high response rates of 92.9% and 96.8%, respectively, though with smaller sample sizes.
- TPO-RAs were associated with rapid platelet recovery in most patients.

## Abstract

Thrombocytopenia is a frequent and clinically significant hematologic manifestation of systemic lupus erythematosus (SLE). A subset of patients develops refractory immune thrombocytopenia (ITP) despite standard therapy, creating a major therapeutic challenge. Targeted agents, including rituximab, belimumab, and thrombopoietin receptor agonists (TPO-RAs), have been used in small studies, but their overall effectiveness in SLE-associated refractory ITP has not been comprehensively evaluated. To systematically review and synthesize evidence on the effectiveness of rituximab, belimumab, and TPO-RAs for refractory ITP in adults with SLE, we conducted a systematic review and meta-analysis of observational studies following a prespecified protocol. Eligible studies included adults with confirmed SLE and refractory ITP treated with rituximab, belimumab, or TPO-RAs. Data were extracted on clinical outcomes, including complete response, partial response, and overall response rate (ORR). A meta-analysis of proportions using fixed-effects models was performed for each treatment category. Methodological quality was assessed using the Newcastle-Ottawa Scale. Eleven studies involving 11 cohorts met the inclusion criteria. Six cohorts (192 patients; pooled ORR 88.5% [170/192]) evaluated rituximab, two cohorts (14 patients; pooled ORR 92.9% [13/14]) evaluated belimumab, and three cohorts (31 patients; pooled ORR 96.8% [30/31]) evaluated TPO-RAs. Rituximab demonstrated a consistently high ORR of 88.5% (170/192) across studies. Belimumab showed an ORR of 92.9% (13/14), although small sample sizes limited evidence. TPO-RAs demonstrated the highest ORR of 96.8% (30/31), with rapid platelet recovery in most patients. Overall study quality was moderate, with larger rituximab cohorts providing the most substantial evidence, whereas belimumab and TPO-RA data were derived from small retrospective studies. Definitions of treatment response varied across studies. Rituximab, belimumab, and TPO-RAs appear to be effective therapeutic options for refractory SLE-associated ITP, with consistently high response rates across available studies. Evidence is strongest for rituximab, while belimumab and TPO-RAs show promising results that require confirmation in larger, well-designed prospective studies. Standardization of response criteria and improved safety reporting are needed to optimize treatment strategies for this challenging clinical condition.