Ropeginterferon alfa-2b 250micrograms/0.5ml solution for injection pre-filled disposable devices

BackgroundPolycythemia 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.AimTo 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.MethodsThis 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.ResultsFive 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.ConclusionRI 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.

Abstract licence: CC BY-NC

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Abstract licence: CC BY

BackgroundRopeginterferon 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.MethodsA 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.ResultsThree 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 ConclusionRopeginterferon 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.

Abstract licence: CC BY-NC