Thrombopoietin Receptor Agonists Plus Immunosuppressive Therapy in Aplastic Anaemia: A Systematic Review and...

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.

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.

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.

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.

The authors have confirmed clinical trial registration is not needed for this submission.