High Initial Dose and Accelerated vs. Slow Titration Ropeginterferon Alfa-2b for Polycythemia Vera: A Meta-Analysis

Ropeginterferon alfa-2b (ropegIFN) is an approved cytoreductive therapy for polycythemia vera (PV). While the current drug label supports a low initial dose with slow titration ("Slow Titration") regimen starting at 50-100 μg with gradual escalation, there is increasing adoption of a high initial dose and accelerated titration (HIDAT) regimen, starting at 250 μg with rapid escalation to 500 μg in 4 weeks. We conducted a systematic review and meta-analysis of ropegIFN studies to derive pooled estimates of efficacy and safety outcomes across HIDAT and Slow Titration studies. We searched MEDLINE, Embase, Web of Science, and ClinicalTrials.gov for literature published up until 3/15/2026. Study selection, data extraction, and risk of bias assessment (ROB2, MINORS, Newcastle-Ottawa Scale) was performed with otto-SR, an AI-powered systematic review platform, with independent human validation. HIDAT achieved significantly higher complete hematologic response (CHR) rates at 3, 6, and 12 months, relative to Slow Titration. Molecular response rates and reductions of JAK2V617F VAF were similarly superior with HIDAT at 6 and 12 months. No significant differences in safety outcomes (adverse events, serious adverse events, trial discontinuations) were observed. These findings support the clinical rationale for HIDAT as a strategy to accelerate hematologic and molecular disease control in PV, while prospective randomized trials are needed to confirm the results.