Low-Dose Prophylaxis versus On-Demand Therapy in Hemophilia Management: A Systematic Review and Meta-Analysis of Clinical Outcomes and Cost-Effectiveness in Resource-Limited Settings

Hemophilia A and B impose a catastrophic burden in resource-limited settings (RLS), where the standard of care—high-dose primary prophylaxis—remains economically inaccessible. Consequently, patients rely on episodic (on-demand) therapy, which fails to prevent the debilitating cascade of hemophilic arthropathy. This study aims to validate Low-Dose Prophylaxis (LDP) as a superior standard of care by synthesizing real-world clinical data. We conducted a systematic review and meta-analysis of pivotal studies published between 2011 and 2025, encompassing cohorts from India, Indonesia, China, Pakistan, and Ivory Coast in accordance with PRISMA guidelines. Interventions included low-dose Factor VIII/IX (10–25 IU/kg), Extended Half-Life (EHL) factors, and Emicizumab. Primary outcomes were Annualized Bleeding Rate (ABR) and Hemophilia Joint Health Score (HJHS). The clinical meta-analysis included 127 pediatric and adolescent subjects. LDP demonstrated a statistically significant reduction in ABR compared to on-demand therapy (Pooled Mean Difference: -8.14; 95% CI: -10.5 to -5.7; p