Ropeginterferon alfa-2b vs standard therapy in polycythemia vera: A meta-analysis of efficacy and safety outcomes

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by excessive blood cell production, which increases the risk of thrombosis. Ropeginterferon alfa-2b (RI) offers potential advantages over standard therapy (ST; including phlebotomy, hydroxyurea, and aspirin) by achieving hematologic and molecular responses. However, its comparative efficacy and safety remain understudied. We hypothesized that RI would improve hematologic and molecular outcomes but may differ in safety profiles compared to ST.

To evaluate the efficacy and safety of RI vs ST in patients with PV, focusing on hematologic response, molecular response, adverse events (AEs), and thrombotic risk.

This Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant meta-analysis included randomized controlled trials comparing RI to ST in adult PV patients. PubMed, EMBASE, ClinicalTrials.gov, and ScienceDirect were searched from inception to July 2025. Outcomes included complete hematological response (CHR), molecular response, AEs leading to discontinuation, JAK2V617F allele burden, thrombotic events, and phlebotomy frequency. Pooled odds ratios (ORs) and MD with 95% confidence intervals (95%CIs) were calculated using random-effects models. Risk of bias was assessed with Cochrane RoB 2; evidence certainty was evaluated via GRADE.

Five studies involving 477 RI and 456 ST patients were included. RI significantly improved CHR (OR = 2.14, 95%CI: 1.18-3.88, P = 0.002) and molecular response (OR = 4.37, 95%CI: 0.99-19.38, P = 0.05), with substantial heterogeneity (I² = 76% and I² = 93%, respectively). AEs leading to discontinuation were higher with RI (OR = 3.89, 95%CI: 1.90-7.97, P = 0.0002; I² = 0%). No significant differences were observed in JAK2V617F allele burden (MD = -7.46, 95%CI: -21.12 to 6.20, P = 0.28; I² = 90%) or thrombotic events (OR = 0.93, 95%CI: 0.45-1.90, P = 0.83; I² = 0%). RI reduced phlebotomy frequency (MD = -1.52, 95%CI: -2.37 to -0.67, P = 0.0005; I² = 0%). Most studies had low to moderate risk of bias; evidence certainty was moderate for CHR and AEs, low for molecular response and thrombotic events, and very low for allele burden.

RI offers superior hematologic and molecular responses compared to ST in PV but is associated with higher discontinuation rates due to AEs. Comparable thrombotic risk and reduced phlebotomy needs highlight its potential, though tolerability requires careful management. The high heterogeneity in certain outcomes and potential for publication bias warrant cautious interpretation of these findings. Further long-term studies are needed to optimize dosing and patient selection.