Psychometric validation and interpretation thresholds of the Hidradenitis Suppurativa Quality of Life (HiSQOL©) questionnaire using pooled data from the phase III BE HEARD I & II trials of bimekizumab in hidradenitis suppurativa

Background Hidradenitis suppurativa (HS) is a chronic, inflammatory skin condition which negatively impacts patients' physical and mental wellbeing. The HS Quality of Life questionnaire (HiSQOL (c)) was developed to assess HS-specific changes in health-related quality of life (HRQoL), one of the six domains of the core outcome set, established by the HS Core Outcomes Set International Collaboration. Objectives To evaluate the psychometric properties of HiSQOL total and domain scores and determine interpretation thresholds to guide score interpretation. Methods Blinded, pooled data from two bimekizumab phase III trials (BE HEARD I & II) in adult patients with moderate-to-severe HS were used to conduct a confirmatory factor analysis (CFA) and to assess convergent validity [correlations with other patient-reported outcomes (PROs)], known-groups validity [grouping patients according to Hurley stage, International Hidradenitis Suppurativa Severity Score System (IHS4) and patient global impression of HS severity scale], reliability [Cronbach's alpha and intraclass correlation coefficients (ICCs)] and responsiveness (sensitivity to change). Clinically meaningful within-patient improvement thresholds were estimated by anchor- and distribution-based analyses. Symptom/impact severity thresholds were estimated by receiver operating characteristic curve analyses. Results The CFA models supported the relevance of the three subscales and an underlying unidimensional concept, validating the total score derivation from all items. HiSQOL subscale and total scores showed good convergent and known-groups validity, with HiSQOL scores being consistently higher (worse HRQoL outcomes) for patients with higher disease severity. HiSQOL demonstrated good internal consistency (Cronbach's alpha >= 0.81 for all scores) and test-retest reliability (ICC 0.73-0.83 across HiSQOL scores). Correlation coefficients between changes in HiSQOL scores and changes in other PRO scores were all positive and statistically significant (P-values < 0.001), with most exceeding 0.30, demonstrating acceptable responsiveness. Clinically meaningful within-patient improvement thresholds were estimated as: 20-21-point decrease for HiSQOL total score (total possible range 0-68), 5-6-point decrease for symptoms (range 0-16), 4-5-point decrease for psychosocial (range 0-20) and 10-11-point decrease for activities-adaptations (range 0-32). Thresholds for different levels of symptom/impact severity were derived. Conclusions The HiSQOL subscale and total scores demonstrated robust psychometric properties, supporting the use of HiSQOL to interpret trial results and inform treatment decisions.