Gulliver, Wayne

Abstract Background Hidradenitis suppurativa (HS) is a chronic, relapsing, debilitating skin disease characterized by deep‐seated nodules, abscesses and tunnels. Objectives To investigate the efficacy of bimekizumab using International Hidradenitis Suppurativa Severity Score System (IHS4) outcomes in patients with moderate to severe HS in the pooled BE HEARD I and II Phase 3 studies. Methods Patients received (initial/maintenance) bimekizumab 320 mg every 2 weeks (Q2W)/Q2W, bimekizumab Q2W/every 4 weeks (Q4W), bimekizumab Q4W/Q4W or placebo/bimekizumab Q2W. Change from baseline (CfB) in IHS4, IHS4 severity stages and the dichotomous IHS4‐55/75/90/100 (an improvement of at least 55%/75%/90%/100% in IHS4 from baseline) are reported to Week 48. Lesion count data by lesion type are reported to Week48. Results In total, 1014 patients were enrolled across BE HEARD I and II. At baseline, mean (standard deviation [SD]) IHS4 for bimekizumab‐treated patients ranged from 33.4 (25.4) for bimekizumab Q2W/Q2W to 36.0 (34.0) for bimekizumab Q2W/Q4W versus 30.6 (21.8) for placebo. At Week16, patients receiving bimekizumab demonstrated greater reductions in mean (SD) IHS4 from baseline, ranging from −17.2 (24.8) for bimekizumab Q4W/Q4W to −17.8 (21.1) for bimekizumab Q2W/Q2W versus −6.1 (16.3) for placebo. Proportions of patients with severe HS at baseline ranged from 83.7% (bimekizumab Q2W/Q2W) to 88.4% (bimekizumab Q2W/Q4W) and decreased by ~50% to Week48 across all treatment arms, ranging from 28.6% (placebo/bimekizumab Q2W) to 34.3% (bimekizumab Q2W/Q2W). Proportions of patients with IHS4 = 0 at Week48 ranged from 23.7% (bimekizumab Q2W/Q4W) to 26.7% (placebo/bimekizumab Q2W). At Week16, IHS4‐55, IHS4‐75, IHS4‐90 and IHS4‐100 thresholds were achieved by greater proportions of patients treated with bimekizumab versus placebo, while comparable improvements were seen across treatment arms from Week16 to Week48. At Week16, lesion counts were lower for patients treated with bimekizumab versus placebo, decreasing to comparable numbers across all groups at Week48. Conclusions Bimekizumab‐treated patients showed improvements across IHS4 outcome measures.

Abstract Background Validated, inclusive and easy‐to‐use outcomes for hidradenitis suppurativa are essential both in the clinical trial setting and clinical practice. The continuous IHS4 is a validated tool that dynamically assesses nodules/abscesses/draining tunnels and classifies disease severity as mild/moderate/severe. However, dichotomous outcomes are often required for clinical trials reporting. Objective To develop and validate a dichotomous outcome based on IHS4 that can be used in clinical trial settings and day‐to‐day clinical practice. Methods De‐identified data from the PIONEER‐I and ‐II studies were accessed through Vivli. Potential IHS4 thresholds were analysed using baseline to Week 12 data from adalimumab‐ and placebo‐treated hidradenitis suppurativa patients in the PIONEER‐I trial. The final threshold was chosen based on its ability to discriminate between patients treated with adalimumab or placebo and its association with reduction in inflammatory lesions. The final threshold was validated using data from baseline to Week 12 from adalimumab‐ and placebo‐treated hidradenitis suppurativa patients in both the PIONEER‐II and the combined PIONEER‐I and ‐II studies. Results The best performing cut‐off for the IHS4 was a 55% reduction of the IHS4 score (IHS4‐55). Patients who achieved the IHS4‐55 had an odd's ratio of 2.00 [95%‐CI 1.26–3.18, p = 0.003], 2.79 (95%‐CI 1.76–4.43, p < 0.001) and 2.16 (95%‐CI 1.43–3.29, p < 0.001) for being treated with adalimumab rather than placebo in PIONEER‐I, PIONEER‐II and the combined dataset, respectively. Additionally, the achievement of the IHS4‐55 was associated with a significant reduction in inflammatory nodules, abscesses and draining tunnels in all analysed datasets. Conclusions IHS4‐55, a novel dichotomous IHS4 version, based on a 55% reduction of the total score was developed. The IHS4‐55 performs similarly to the HiSCR in discriminating between adalimumab‐ and placebo‐treated hidradenitis suppurativa patients and shows significant associations with reductions in lesion counts. Moreover, the IHS4‐55 addresses some of the HiSCR drawbacks by dynamically including draining tunnels in a validated manner. By allowing the analysis of hidradenitis suppurativa patients with an abscess and nodule count below 3 but many draining tunnels, this outcome measure will improve inclusivity in clinical trials.

Background Real-world knowledge of the burden of hidradenitis suppurativa (HS) on patients remains limited. Objectives To measure the impact of adalimumab on moderate-to-severe HS patients’ health-related quality of life (HRQoL) and work productivity. Methods In 23 Canadian centres, 138 adults with moderate-to-severe HS requiring a change in ongoing therapy were treated with adalimumab for up to 52 weeks as per the physician’s practice. Patient-reported outcome measures (PROMs) were obtained at baseline, weeks 24 and 52 to measure overall HRQoL, HS severity, levels of anxiety and depression, impact and symptoms of HS, work productivity and activity impairment. A post-hoc analysis further explored the PROMs by abscess and inflammatory nodule (AN) count at baseline (≤5, low; 6–10, medium; ≥11, high). Results From baseline to weeks 24 and 52, all PRO overall scores improved significantly ( P ≤ .0023). The number of patients reporting “good disease control” and “complete disease control” increased from 9.7% to 66.4% over 52 weeks. The score in Health Utility Index Mark 3 (HUI3) pain attribute meaningfully decreased over 52 weeks (mean difference ≥.05). The HS symptoms skin “tenderness” and “itchiness” improved the most. Work productivity loss and activity impairment improved by approximately 20% over 52 weeks. Disease burden improved more in 24 week responders with low and medium AN counts at baseline than in those with high AN count or in 24 week nonresponders. Conclusion At week 24 and maintained at week 52 in a real-world setting, adalimumab meaningfully improved HRQoL, work productivity, and activity impairment in moderate-to-severe HS patients.