Thrombopoietin Receptor Agonists Plus Immunosuppressive Therapy in Aplastic Anaemia: A Systematic Review and Meta‐Analysis

Background: Immunosuppressive therapy (IST) is standard first-line treatment for severe aplastic anaemia (AA) in patients ineligible for allogeneic transplantation. Thrombopoietin receptor agonists (TPO-RAs) are increasingly added to IST to improve haematologic recovery, but long-term safety remains uncertain. Methods: We conducted a PRISMA-guided systematic review and meta-analysis. MEDLINE, EMBASE and CENTRAL were searched from inception to April 2025. Randomised controlled trials and observational studies comparing TPO-RA plus IST with IST alone were analysed separately using random-effects models. The primary outcome was overall haematologic response at 6 months; secondary outcomes included response at 3 and 12 months, complete response, survival, relapse and clonal evolution. Results: Twenty studies (2 randomised and 18 observational) were included. In randomised trials, TPO-RA plus IST showed a non-significant trend towards higher overall response at 6 months (OR 2.01; 95% CI 0.76-5.28), while complete response was significantly higher at 3 and 6 months. Observational studies consistently demonstrated higher overall and complete response rates. No significant differences were observed in survival, relapse or clonal evolution. Conclusion: Limited randomised evidence does not demonstrate statistically significant benefit across all outcomes, while observational data suggest potential haematologic advantages. Further high-quality trials are required to clarify the effectiveness and long-term safety of adding a TPO-RA to IST in AA. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.