Ropeginterferon dose-escalation strategies in polycythemia vera: a systematic review and meta-analysis

Ropeginterferon alfa-2b is increasingly used as a long-acting interferon therapy for polycythemia vera (PV), providing hematologic and molecular benefits. However, clinical studies have implemented different dose-escalation strategies, and their impact on outcomes has not been systematically evaluated. A systematic search of PubMed, Embase, and the Cochrane Library (September 24, 2025) identified studies reporting clinical outcomes of ropeginterferon in PV. Nine studies met eligibility criteria. Two reviewers independently extracted data, and meta-analyses were conducted using random-effects models. Subgroup analyses compared slow dose-up (SDU) and rapid dose-up (RDU) regimens at 1-, 2-, and 3-year follow-up when available. The pooled 1-year complete hematologic response (CHR) rate was 0.59 (95% CI, 0.47–0.71). RDU regimens yielded significantly higher CHR than SDU at both 1 year (0.67 vs. 0.41; p < 0.001) and 2 years (0.75 vs. 0.63; p = 0.038). Molecular response (MR) also favored RDU at 1 year (0.59 vs. 0.36; p < 0.001), with differences diminishing at 2 years. The pooled 1-year reduction in JAK2 V617F allele burden was − 22.2% (95% CI, − 34.2% to − 10.2%; p < 0.001). Safety outcomes were favorable, with low rates of thrombosis (4%), serious adverse events (5%), and treatment discontinuation (7%). Ropeginterferon alfa-2b provides meaningful hematologic and molecular responses with an acceptable safety profile in PV. Rapid dose-escalation facilitates earlier CHR and MR without increasing toxicity, suggesting titration speed as an important determinant of early treatment optimization.