Prevalence and Clinical Characteristics of Vitiligo-Associated Hearing Loss Among Patients in a Phase 2 Clinical Trial of Povorcitinib.

INTRODUCTION: Patients with vitiligo reportedly have an increased risk of sensorineural hearing loss (SNHL), driven by the loss of extracutaneous melanocytes in the inner ear. In a phase 2 dose-ranging study, the oral, selective Janus kinase 1 inhibitor povorcitinib demonstrated substantial repigmentation in patients with extensive nonsegmental vitiligo through 52 weeks of treatment. This exploratory post hoc analysis of the phase 2 study evaluated the prevalence of hearing loss among enrolled patients and examined their associated demographic and clinical characteristics, as well as their audiometric response to povorcitinib. METHODS: SNHL was defined as a bone-conduction threshold of ≥ 25 dB in either ear and was assessed using all-frequencies average (AFA: 250, 500, 1000, 2000, 3000, 4000, 6000, 8000 Hz), pure-tone average (PTA: 500, 1000, 2000, 4000 Hz), and high-frequencies average (HFA: 2000, 3000, 4000, 6000, 8000 Hz). RESULTS: Of 162 patients assessed for hearing loss, SNHL prevalence at baseline was 10.5% (AFA), 11.7% (PTA), and 14.2% (HFA). Patients with versus without SNHL were significantly older and had significantly greater facial involvement. Following up to 52 weeks of povorcitinib treatment, bone-conduction hearing thresholds improved across all frequency ranges, although no definitive conclusions can be drawn. At week 52, mean percentage change from baseline in the left and right ears was as follows: AFA, - 18.7% (P = 0.08) and - 16.1% (P = 0.10); PTA, - 13.9% (P = 0.18) and - 7.2% (P = 0.25); and HFA, - 11.0% (P = 0.21) and - 12.6% (P = 0.18), respectively. CONCLUSION: SNHL was common in this patient population, suggesting that audiologic evaluation may be appropriate for some patients with vitiligo to support early detection and management of hearing loss. Changes in hearing with povorcitinib treatment require confirmation in larger patient populations. Graphical abstract available for this article. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04818346.