Patient-Reported Pain Reduction Offers New Path to Predict Treatment Success in Hemophilia
A new post hoc analysis from the PERSEPT 1 trial offers compelling evidence supporting the use of eptacog beta for managing acute pain during bleeding episodes (BEs) in patients with hemophilia A or B with inhibitors (PwHABI). The data highlight both the analgesic benefit of the therapy and the diagnostic value of patient-reported pain reduction for predicting treatment outcomes.
Among adolescent and adult PwHABI treated with 75 or 225 µg/kg initial dose regimens (IDRs), eptacog beta led to significant pain reductions within 3 hours of the first infusion. Across all age and dose groups, mean pain scores dropped between 30% and 58% at 3 hours, with further improvement through 24 hours. Notably, these outcomes were achieved without the use of analgesics in the majority of cases (420 of 468 BEs).
Mean baseline pain scores, measured using a 0- to 100-mm visual analogue scale (VAS), ranged from 26.5 to 42.2 mm. By 24 hours posttreatment, VAS scores fell as low as 0.0 to 2.0 mm across study subgroups. The associated treatment success rates rose concurrently, with 97% to 100% of BEs rated as having ‘good’ or ‘excellent’ hemostasis outcomes at 24 hours.
Pain relief varied depending on the initial severity of pain. PwHABI with higher baseline VAS scores (67-100 mm) required larger absolute reductions—averaging 58.9 mm—to conclude treatment, compared with those who began with lower pain scores. Despite the difference in absolute numbers, percentage reductions were relatively consistent, suggesting that a perceived threshold of improvement, rather than fixed pain levels, informed patients’ decisions to cease therapy.
This correlation reinforces the importance of baseline pain stratification in future clinical trial designs and coverage evaluations.
Receiver operating characteristic (ROC) analysis identified a 44% reduction in VAS pain score at 3 hours as an optimal predictor of treatment success. This threshold yielded a sensitivity of 80.1%, specificity of 84.6%, positive predictive value of 85.8%, and negative predictive value of 78.6%. With an area under the curve (AUC) of 0.881, the analysis confirms that early pain relief, quantified via VAS, can serve as a reliable surrogate for bleed resolution in PwHABI.
This study underscores the potential for integrating patient-reported pain outcomes into both clinical and reimbursement frameworks. The clear linkage between VAS score reductions and hemostatic efficacy offers a pragmatic endpoint for evaluating response to bypassing agents like eptacog beta.
The findings suggest that early and significant pain relief—especially without adjunctive analgesics—could serve as a meaningful indicator of therapeutic value and inform coverage criteria. The 44% VAS reduction threshold may offer a quantifiable metric to assess treatment effectiveness in real-world settings.
Reference
Buckner TW, Kessler C, Castaman G, et al. Pain reduction following eptacog beta treatment of bleeding episodes in adolescents and adults with haemophilia A or B complicated by inhibitors. Haemophilia. Published online June 19, 2025. doi:10.1111/hae.70077
