Ropeginterferon alfa-2b in Polycythemia Vera: A systematic review and meta-analysis.
Key claim: Ropeginterferon alfa-2b is not significantly better than hydroxyurea for hematologic or molecular responses in PV, but is superior to phlebotomy alone for complete hematologic response, partial molecular response, and JAK2V617F allele-burden reduction.
Abstract
BACKGROUND: Ropeginterferon alfa-2b, a novel monopegylated interferon with improved pharmacokinetics, has emerged as a promising cytoreductive agent for managing polycythemia vera (PV). Despite increasing adoption, evidence synthesis of its efficacy and safety compared to standard care remains limited. The manuscript aimed to evaluate the efficacy of ropeginterferon alfa-2b in comparison to standard treatment options, including hydroxyurea and phlebotomy, in achieving complete hematologic response, partial molecular response (PMR), and reducing JAK2V617F allele burden in patients with PV. METHODS: A systematic search of 4 databases was conducted up to April 2025, following PRISMA 2020 guidelines. Randomized controlled trials (RCTs) comparing ropeginterferon alfa-2b with standard therapies in PV patients were included. Meta-analyses were performed using random-effects models to derive odds ratios for dichotomous outcomes and mean differences (MDs) for continuous outcomes. Sensitivity and subgroup analyses were conducted, and risk of bias was assessed using RoB 2.0. RESULTS: Three RCTs comprising 522 patients were analyzed. Ropeginterferon alfa-2b showed no statistically significant advantage overall or over hydroxyurea for complete hematological response (CHR), PMR, or JAK2 allele burden reduction. However, subgroup analyses revealed significant benefits over phlebotomy alone in all 3 outcomes: CHR (odds ratio [OR] 3.05; 95% confidence interval [CI]: 1.36-6.80; P = .007), PMR (OR 36.34; 95% CI: 2.11-625.93; P = .01), and allele burden reduction (MD -13.70; 95% CI: -19.24 to -8.16; P < .00001). CONCLUSION: Ropeginterferon alfa-2b demonstrates no statistically significant difference compared to hydroxyurea, but gives better outcomes over phlebotomy in short-term efficacy for PV management. Its favorable molecular and hematologic outcomes support its role as a disease-modifying therapy, particularly in low-risk patients. However, larger and longer-term trials are needed to confirm these benefits across broader populations.
Why this matters
This meta-analysis sharpens the PV-specific evidence base for ropeginterferon alfa-2b by separating what is proven (molecular and hematologic superiority over phlebotomy alone) from what remains unproven (superiority over hydroxyurea). For a subtype where frontline cytoreduction choice is actively contested — and where parallel head-to-head trials (MITHRIDATE, Givinostat vs HU) are ongoing — this recalibrates the disease-modification narrative that has increasingly favored ropeg. It reinforces that ropeg’s clearest incremental value in PV natural history is versus phlebotomy-only management, not necessarily versus HU.