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Importance Accurate classification and reliability in assessment for lesions of hidradenitis suppurativa (HS) by investigators is critical to the determination of responder status and to overall data quality in clinical trials. Objective To establish consensus-based morphological definitions of HS lesions and guidance statements that standardize investigator lesion assessments for implementation in clinical trials. Evidence Review Health professionals (primarily dermatologists) with expertise in the measurement of HS disease activity as well as novice raters completed a preliminary questionnaire in which participants were asked to assess images of HS lesions and provide qualitative feedback on their decision making. Based on this feedback, detailed morphologic definitions for lesions and guidance statements that standardize lesion assessments were formulated and presented for consensus voting in 2 electronic Delphi surveys. A virtual group discussion after round 1 supported participants in round 2 voting. Findings Response rates were 84.7% (50 of 59), 86.0% (43 of 50), and 90.9% (40 of 44) in the preliminary, electronic Delphi round 1, and electronic Delphi round 2 surveys, respectively. Morphological definitions for 11 lesion types achieved the prespecified 70% consensus threshold, with 9 definitions reaching at least 90% agreement. After 2 electronic Delphi rounds, 16 of 18 guidance statements achieved the prespecified consensus threshold, with 13 statements receiving endorsement from more than 80% of participants. Two guidance statements related to assessment of tunneled plaques with multiple openings and assessment of scalp lesions failed to reach consensus. Conclusions and Relevance Common morphologic definitions and guidance that standardize assessment of HS lesions can be implemented in clinical trial protocols and investigator trainings with the goals of improving accuracy and reliability of investigator ratings.

Abstract Background The results of a previous phase IIa trial suggested efficacy of the anti-C5a compound vilobelimab in a small number of patients with severe hidradenitis suppurativa (HS) refractory to adalimumab treatment. Objectives To study the efficacy of vilobelimab in a larger-scale randomized phase IIb trial (SHINE) of patients with moderate-to-severe HS. Methods In total, 177 patients with moderate-to-severe HS were treated either with placebo or one of four doses of vilobelimab, a monoclonal antibody that targets the complement split product C5a. Hidradenitis Suppurativa Clinical Response (HiSCR) at 16 weeks was the primary endpoint. Those who achieved HiSCR switched to open-label low-dose vilobelimab; those who did not were switched to medium-dose vilobelimab. The trial was registered with the EU Clinical Trials Register (EudraCT number 2017-004501-40) and ClinicalTrials.gov (NCT03487276). Results The study did not meet the primary endpoint, perhaps due, in part, to an unexpectedly high HiSCR placebo response rate of 47.1%. HS flares decreased and post hoc analysis showed that high-dose vilobelimab significantly decreased the median draining tunnel counts and IHS4 score by 63%. Following the switch to medium-dose vilobelimab at week 16, 45.5% of those who did not respond to treatment achieved HiSCR at week 40. Conclusions Compared with placebo, vilobelimab treatment did not result in significant HiSCR improvements in patients with moderate-to-severe HS. Post hoc analysis revealed significant effects for the highest tested dose on draining tunnel reduction and IHS4 score, which captures reductions in draining tunnels. These findings warrant further investigation.

Importance Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a substantial burden. Standardized global prevalence estimates and data on associated sociodemographic and risk factors are lacking. Objective To estimate the global prevalence of HS and study differences in prevalence by age, sex, geographical location, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), smoking status, gross domestic product (GDP), and Human Development Index (HDI). Data Sources and Study Selection Included studies were conducted using the standardized Global Hidradenitis Suppurativa Atlas methodology with finalized data collection before May 19, 2023. Studies were required to use a population-based sampling method and conduct clinical confirmation of HS diagnosis following a screening questionnaire. Data Extraction and Synthesis Data were independently extracted from relevant studies by 2 reviewers (D.B. and C.E.M.) using a standardized form. Extracted variables included geographic location, age, sex, BMI (median and BMI >30), smoking status, HS prevalence estimates (with 95% CIs), GDP, and HDI. A proportional meta-analysis using a random-effects model was conducted on the included studies. Main Outcomes and Measures The primary outcome was the point prevalence of HS, confirmed by clinical examination. Secondary outcomes included differences in HS prevalence by sex, age, BMI category, smoking status, and country-level socioeconomic indicators (GDP and HDI). All outcomes were prespecified before data analysis. Results The sample included 22 743 participants, identifying 247 patients with HS, across 25 studies in 23 countries spanning 6 continents. The median proportion of female patients with HS was 55.6%, and the median age was 34.5 years. While the prevalence estimates showed considerable inconsistency ( I 2 > 75%; τ 2 = 0.747), the overall random-effects global prevalence of HS was 0.99% (95% CI, 0.67%-1.46%). Female sex was the only factor observed to be associated with the prevalence estimates (β = 1.02; 95% CI, 1.01-1.03). Conclusions and Relevance In this meta-analysis, an estimated global prevalence of HS between 0.67% and 1.46% surpassed previous global estimates. Substantial global variations in HS prevalence were also observed. Female sex was the only factor associated with prevalence in this sample. Future studies assessing genetic, environmental, and etiological factors are warranted to explain the heterogeneity in prevalence.

ABSTRACT Background Secukinumab, a fully human, monoclonal antibody targeting interleukin‐17A, is approved for moderate‐to‐severe HS in adults. This study evaluated pharmacokinetics (PK), high‐sensitivity C‐reactive protein (hsCRP) changes, and safety of secukinumab over 52 weeks in SUNSHINE and SUNRISE Phase 3 trials. Methods An exploratory analysis of pooled Phase‐3 trials evaluated serum PK and safety of secukinumab 300 mg every 2 (SECQ2W) or 4 weeks (SECQ4W). A population PK model assessed the effects of body weight, disease severity, and baseline hsCRP on secukinumab serum concentration. Exposure–response analysis assessed the relationship between predicted PK and HS clinical response [HiSCR]. No confirmatory statistical testing was performed. Results Mean serum trough concentration at Weeks 16, 24, and 52 was ~2‐fold higher with SECQ2W vs. SECQ4W. At Week 16, exposure overlap was high, with an estimated numerical increase in HiSCR of ~3% for SECQ2W over SECQ4W. At Week 52, HiSCR levels plateaued. At Week 16, hsCRP decreased from 18.6 ± 26.3 mg/L to 12.8 ± 18.0 mg/L (SECQ2W), 15.9 ± 27.6 mg/L to 11.5 ± 18.4 mg/L (SECQ4W), and remained unchanged with placebo (14.4 ± 22.5 mg/L to 14.7 ± 23.8 mg/L); reductions were sustained through Week 52. Higher body weight, disease severity, and baseline hsCRP were associated with lower secukinumab serum concentrations. Secukinumab immunogenicity was low (< 1%), with no new safety signals. Conclusion Secukinumab serum concentrations in patients with HS varied with body weight, disease severity, and baseline hsCRP. SECQ2W may benefit certain patients. Secukinumab reduced hsCRP through Week 52. The safety profile of secukinumab was consistent with other approved indications, with no apparent dose–response relationship observed. Trial Registration NCT03713619 (Novartis study code CAIN457M2301). NCT03713632 (Novartis study code CAIN457M2302)

Abstract Background The SUNSHINE and SUNRISE phase III trials demonstrated sustained clinical efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa (HS) through 52 weeks. Patients completing the core trials could enter a 4-year extension trial. Objectives To evaluate the long-term efficacy, safety/tolerability and maintenance of clinical response to secukinumab through week 104 in the extension trial. Methods Patients with a hidradenitis suppurativa (HS) clinical response (HiSCR) at week 52 of the core trials (extension trial baseline visit) entered a randomized withdrawal period. HiSCR responders receiving subcutaneous secukinumab 300 mg every 2 or 4 weeks (SECQ2W/SECQ4W) through week 52 in the core trials were randomized 2 : 1 to continue secukinumab (SECQ2W-R-Q2W or SECQ4W-R-Q4W) or receive placebo (SECQ2W-R-PBO or SECQ4W-R-PBO) through week 104. The primary endpoint was time to loss of response (LOR; newly defined for this trial) through week 104 in week 52 HiSCR responders (SECQ2W-R-Q2W vs. SECQ2W-R-PBO and SECQ4W-R-Q4W vs. SECQ4W-R-PBO). Time to LOR was tested at 1.25% (one-sided) for each comparison (one-sided familywise alpha of 2.5%) through week 104. If LOR was met, patients could remain in the trial on open-label secukinumab treatment. Additional endpoints included safety and HiSCR. The trial was registered with ClinicalTrials.gov (NCT04179175). Results Overall, 84.3% of patients who completed the core trials entered the extension trial; 55.9% were week 52 HiSCR responders. The primary endpoint was not met for either secukinumab dosing regimen. The estimated risk reduction for LOR was 13% (SECQ2W-R-Q2W vs. SECQ2W-R-PBO; one-sided P = 0.25) and 30% (SECQ4W-R-Q4W vs. SECQ4W-R-PBO; one-sided P = 0.04). The median time to LOR was numerically longer in the secukinumab arms vs. placebo {SECQ2W-R-Q2W [283 days; 95% confidence interval (CI) 176, –] vs. SECQ2W-R-PBO [239 days; 95% CI 120, –]; SECQ4W-R-Q4W [365 days 95% CI 225, –] vs. SECQ4W-R-PBO [171 days; 95% CI 113–337]}. In week 52 HiSCR responders reporting LOR, 44% (SECQ2W-R-Q2W), 58% (SECQ2W-R-PBO), 40% (SECQ4W-R-Q4W) and 34% (SECQ4W-R-PBO) were achieving HiSCR at the time of LOR. Overall, the safety of secukinumab was consistent with the core trials. Conclusions The primary endpoint of this trial was not met. HiSCR was maintained in many patients at the time of LOR. The safety of secukinumab was consistent with the previously characterized safety profile in the core trials.

AbstractIntroductionThe International Hidradenitis Suppurativa Severity Score System (IHS4) is a validated tool that measures inflammatory lesions, including draining tunnels, in hidradenitis suppurativa (HS).ObjectiveTo evaluate secukinumab efficacy using IHS4 in patients with moderate to severe HS.MethodsData from the SUNSHINE and SUNRISE trials, which assessed subcutaneous secukinumab 300 mg every 2 (SECQ2W) and 4 (SECQ4W) weeks in adults with moderate to severe HS, were analyzed. Assessments included changes from baseline in IHS4 and severity classification up to Week 52; IHS4‐55, IHS4‐75, IHS4‐90 responses (55%, 75% and 90% reduction in IHS4) and concordance between IHS4‐55 and HS clinical response (HiSCR), at Weeks 16 and 52.ResultsIn total, 1084 patients (SECQ2W = 361; SECQ4W = 360; placebo = 363) were analyzed. At Week 16, SECQ2W and SECQ4W demonstrated a numerically higher reduction in IHS4 from baseline versus placebo (adjusted mean [95% CI]: −10.80 [−12.30 to −9.30] and −9.46 [−10.96 to −7.96] vs. −4.92 [−6.43 to −3.41]); the reduction was maintained until Week 52 in both dose regimens. A greater proportion of patients achieved IHS4‐55 with SECQ2W (43.4%) and SECQ4W (39.5%) versus placebo (31.5%) at Week 16, with further improvement at Week 52. Similar trends were observed for IHS4‐75 and IHS4‐90 responses. While no patients had mild disease based on IHS4 (80.7% had severe and 19.3% had moderate HS) at baseline, a greater proportion of patients were categorized as having mild disease at Week 16 in the SECQ2W (25.9%) and SECQ4W (24.0%) groups versus placebo (16.4%); this trend continued up to Week 52 in both dose regimens. Strong concordance (>85%) was observed between IHS4‐55 and HiSCR.ConclusionsBoth SECQ2W and SECQ4W demonstrated efficacy in improving treatment response as measured by IHS4 and reducing disease severity versus placebo at Week 16 and these improvements were sustained through Week 52. These findings support that the dynamic and dichotomous IHS4 can efficiently detect treatment response changes in clinical trial settings.Clinical Trials RegistrationSUNSHINE (NCT03713619); SUNRISE (NCT03713632).

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.

Abstract Background Nearly half of patients with hidradenitis suppurativa (HS) report dissatisfaction with their treatment. However, factors related to treatment satisfaction have not been explored. Objectives To measure associations between treatment satisfaction and clinical and treatment-related characteristics among patients with HS. Methods Treatment satisfaction was evaluated utilizing data from a cross-sectional global survey of patients with HS recruited from 27 institutions, mainly HS referral centres, in 14 different countries from October 2017 to July 2018. The primary outcome was patients’ self-reported overall satisfaction with their current treatments for HS, rated on a five-point scale from ‘very dissatisfied’ to ‘very satisfied’. Results The final analysis cohort comprised 1418 patients with HS, most of whom were European (55%, 780 of 1418) or North American (38%, 542 of 1418), and female (85%, 1210 of 1418). Overall, 45% (640 of 1418) of participants were either dissatisfied or very dissatisfied with their current medical treatment. In adjusted analysis, patients primarily treated by a dermatologist for HS had 1·99 [95% confidence interval (CI) 1·62–2·44, P &lt; 0·001] times the odds of being satisfied with current treatment than participants not primarily treated by a dermatologist. Treatment with biologics was associated with higher satisfaction [odds ratio (OR) 2·36, 95% CI 1·74–3·19, P &lt; 0·001] relative to treatment with nonbiologic systemic medications. Factors associated with lower treatment satisfaction included smoking (OR 0·78, 95% CI 0·62–0·99; active vs. never), depression (OR 0·69, 95% CI 0·54–0·87), increasing number of comorbidities (OR 0·88 per comorbidity, 95% CI 0·81–0·96) and increasing flare frequency. Conclusions There are several factors that appear to positively influence satisfaction with treatment among patients with HS, including treatment by a dermatologist and treatment with a biologic medication. Factors that appear to lower treatment satisfaction include active smoking, depression, accumulation of comorbid conditions and increasing flare frequency. Awareness of these factors may support partnered decision making with the goal of improving treatment outcomes. What is already known about this topic? Nearly half of patients with hidradenitis suppurativa report dissatisfaction with their treatments. What does this study add? Satisfaction with treatment is increased by receiving care from a dermatologist and treatment with biologics.Satisfaction with treatment is decreased by tobacco smoking, accumulation of comorbid conditions including depression, and higher flare frequency. What are the clinical implications of this work? Awareness of the identified factors associated with poor treatment satisfaction may support partnered decision making and improve treatment outcomes.