Introduction: Steroid-refractory acute graft-versus-host disease (SR-aGVHD) remains a significant post-transplant challenge, often unresponsive to conventional therapies. Among the new treatment options, Ruxolitinib, an FDA-approved Janus kinase (JAK) inhibitor, and Remestemcel-L, a recently FDA-approved mesenchymal stromal cell therapy, offer distinct mechanisms of action. Ruxolitinib targets the JAK-STAT pathway, while Remestemcel-L seeks to restore immune balance through cellular repair. This systematic review and meta-analysis evaluates the efficacy and safety of both therapies, providing insights into their therapeutic potential and informing clinical decisions for managing this life-threatening condition.

Methods: A systematic search of MEDLINE, EMBASE, and CENTRAL was conducted for studies on Ruxolitinib and Remestemcel-L in SR-aGVHD up to August 2025. Meta-analysis was performed using Stata 18.0, with risk of bias assessed using ROBS 2.0.

Results: Of 1,247 screened studies, 11 met the inclusion criteria, involving 2,732 patients (1,993 in the treatment group and 523 in the control group). Among treatment groups, 644 patients received Remestemcel-L, and 1,349 received Ruxolitinib. In terms of efficacy, Remestemcel-L had an odds ratio (OR) for complete remission of 0.62 (95% CI: 0.42–0.92), while Ruxolitinib showed an OR of 1.37 (95% CI: 0.94–1.98). For overall remission, Remestemcel-L had an OR of 3.41 (95% CI: 1.88–6.21), compared to 2.13 (95% CI: 1.44–3.15) for Ruxolitinib. Regarding overall survival, Remestemcel-L showed an OR of 3.92 (95% CI: 0.78–19.75), while Ruxolitinib had an OR of 4.46 (95% CI: 1.35–15.52). In terms of safety, Remestemcel-L had an Risk Ratio (RR) for hematologic adverse drug reactions (ADR) of 1.20 (95% CI: 0.42–3.52), compared to 1.46 (95% CI: 0.94–2.26) for Ruxolitinib. For cardiac ADR, Remestemcel-L had an RR of 0.64 (95% CI: 0.33–1.26), while Ruxolitinib showed an RR of 0.99 (95% CI: 0.69–1.43). Hepatic ADR had an RR of 1.17 (95% CI: 0.10–14.11) for Remestemcel-L, and 1.82 (95% CI: 0.42–8.81) for Ruxolitinib. For neurological ADR, the RR for Remestemcel-L was 0.95 (95% CI: 0.51–1.76), and for Ruxolitinib, it was 0.94 (95% CI: 0.65–1.36). Both treatments significantly improved quality of life.

Conclusion: Both Ruxolitinib and Remestemcel-L demonstrate significant efficacy in treating steroid-refractory acute graft-versus-host disease, with Remestemcel-L showing superior outcomes in complete and overall remission. Both therapies exhibit favorable safety profiles, though clinical decisions should consider the differences in adverse events. Risk of Bias was moderate in the analyzed studies.

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2025
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