The concept of a therapeutic window of opportunity, defined as the period from symptom onset during which treatment initiation yields the most favorable patient outcomes, is applied in routine clinical practice across a range of inflammatory conditions. It has become an increasingly important area of interest in hidradenitis suppurativa (HS), a disease in which recurrent inflammation and accumulating damage can lead to irreversible destruction of skin architecture. Biologic therapies, aiming to suppress the inflammatory burden and prevent disease progression, are currently only permitted in moderate to severe HS. However, as there is no consensus definition of moderate disease, physicians may face uncertainty about when to consider or switch biologic therapy. To identify the boundaries of the window of opportunity within HS, global HS experts have developed frameworks for defining moderate HS and disease progression. It is proposed that prompt medical treatment should be administered to patients with moderate HS, defined as patients with inadequate control of HS symptoms on conventional therapies, or one inflamed skin tunnel (draining/non-draining), or four or more inflammatory lesions (including inflammatory nodules and abscesses) involving two or more anatomic areas. Furthermore, the proposed definition for disease progression is the development of one or more new tunnel(s) and/or the extension of existing tunnels, or development of one or more persistent HS lesions in an anatomical region not previously affected, or any increase in the number of persistent HS lesions in an affected anatomical region. The proposed frameworks aim to provide practical advice to physicians and support targeting the window of opportunity during routine clinical practice.

Abstract Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with complex immune dysregulation. While previous studies have reported tertiary lymphoid structures (TLS) and IgA-producing B cells in HS skin lesions, the pathogenic role of IgA autoantibodies remains insufficiently characterized. Here, we demonstrate that lesional skin from patients with HS exhibits elevated expression of IGHA1, IGHA2, and J chain, as confirmed by qPCR, immunofluorescence, and Western blot analyses. Single-cell RNA sequencing identified local plasma cells and B cells as the primary source of IgA. Autoantigen profiling revealed a diverse repertoire of IgA autoantibodies targeting nuclear, cytoplasmic, and membrane antigens, with levels correlating with disease severity and other clinical manifestations. We identified IgA autoantibodies binding to CD68⁺ macrophages, which induced secretion of TNF, IL-6, and IL-1β and upregulated inflammasome and profibrotic pathways. Anti-neutrophil extracellular trap (NET) IgA was elevated in HS and promoted NET formation, establishing a pathogenic feedback loop. NET–IgA immune complexes induced macrophages to secrete CCL18, driving collagen production by fibroblasts and promoting a type I interferon (IFN) gene signature. IgA immune complexes presented by myeloid dendritic cells activated CD4⁺ T cells, triggering IFN-γ production and further amplifying local inflammation. Notably, supernatants from macrophages exposed to IgA were able to polarize naïve CD4⁺ T cells toward a Th17 phenotype, linking innate immune activation to the expansion of pathogenic adaptive immune responses. Direct exposure of fibroblasts to NET–IgA complexes triggered expression of adhesion molecules, chemokines, and regulators of adaptive immunity. Together, these findings uncover a role for IgA autoantibodies in HS, implicating them as central drivers of chronic inflammation, fibrosis, and immune crosstalk across neutrophils, macrophages, fibroblasts, and T cells.

Although therapeutic options for hidradenitis suppurativa (HS) continue to expand, unmet needs remain substantial. We evaluated the efficacy and safety of povorcitinib (an oral, highly selective Janus kinase 1 (JAK1) inhibitor) in patients with moderate to severe HS in two randomized trials. STOP-HS1 and STOP-HS2 were identically designed, randomized, double-blind, placebo-controlled phase 3 trials. Adults with moderate to severe HS were randomized 2:2:1:1 to once-daily treatment through week 54: povorcitinib 45 mg; povorcitinib 75 mg; placebo with crossover at week 12 to povorcitinib 45 mg; or placebo with crossover at week 12 to povorcitinib 75 mg. The primary endpoint was HiSCR50 (≥50% decrease in total abscess and inflammatory nodule count, with no increase from baseline in abscess or draining tunnel count) at week 12. STOP-HS1/STOP-HS2 enrolled 608/619 patients, respectively. In both studies, both povorcitinib doses met the primary endpoint; in STOP-HS1, 82/204 (40%) patients in the povorcitinib 45-mg group and 82/202 (41%) in the 75-mg group versus 60/202 (30%) in the placebo group achieved HiSCR50 (OR (95% CI) 45 mg: 1.6 (1.1-2.5), P = 0.0240; 75 mg: 1.6 (1.1-2.4), P = 0.0214); corresponding values for STOP-HS2 were 88/208 (42%) and 88/208 (42%) versus 58/203 (29%; OR (95% CI) 45 mg: 1.8 (1.2-2.8), P = 0.0035; 75 mg: 1.9 (1.2-2.8); P = 0.0033). Through week 12, across STOP-HS1/STOP-HS2, serious treatment-emergent adverse events (AEs) occurred in 1-2% of patients across povorcitinib doses and in 2-3% with placebo; through week 54, serious AEs occurred in 5%/6% of patients receiving 45-mg/75-mg povorcitinib, respectively. The most frequent AEs among patients treated with 45-mg/75-mg povorcitinib were acne (17%/20%), nasopharyngitis (10%/12%) and upper respiratory tract infection (11%/10%). One death of undetermined etiology was reported and deemed unrelated to treatment. No new or unexpected safety findings were identified. Oral povorcitinib demonstrated significant improvements in HiSCR50 versus placebo and a favorable safety profile in patients with moderate to severe HS. ClinicalTrials.gov registration: NCT05620823 and NCT05620836 .

Hidradenitis suppurativa (HS) is a chronic, systemic, immune-mediated disease requiring multimodal care, which is crucial for raising awareness and advancing treatment. This project aimed to establish consensus among HS experts to define HS Competence Centers (HSCC) criteria using the Delphi consensus method. Overall, 22 global HS experts (3 patient representatives and 19 healthcare professionals [HCPs]) from 16 countries across 5 continents were invited to participate. Subsequently, a three-step Delphi polling was conducted among the HS experts from 20 May 2024 to 8 July 2024. A 50

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease characterized by painful nodules and tunnels, which are predominantly found in intertriginous skin areas such as the axillary, inguinal and anogenital regions. The condition significantly impacts patients' quality of life owing to its chronicity and debilitating nature. While a combined medical and surgical approach is recommended for severe cases, misconceptions exist regarding the role and timing of surgery for HS, often influenced by patient fear and hesitation. A comprehensive, multidisciplinary approach involving a multimodal therapeutic strategy is essential for successful HS outcomes. The decision to opt for surgery depends on various factors such as disease severity, lesion characteristics, anatomical location and patient preferences. Although surgery remains a cornerstone in managing recurrent and severe cases of HS, surgical interventions, when combined with targeted medical therapies, can lead to favourable outcomes and improved disease control. This review aims to guide clinicians in decision making around the suitability of surgery by providing a framework for surgery in HS in the context of various clinical scenarios.

BACKGROUND:Adalimumab is widely used for hidradenitis suppurativa (HS), but treatment durability varies and predictors of sustained benefit remain uncertain. OBJECTIVE:To identify clinical and laboratory factors associated with adalimumab treatment durability in HS. METHODS:We retrospectively studied 135 adults with HS who initiated adalimumab as first biologic therapy across three academic centers from 2013 to 2023. Outcomes were categorized as primary failure (12-24 weeks), secondary failure (24 weeks-2 years), or sustained response (>2 years) based on discontinuation for inefficacy. Predictors of treatment durability were evaluated using ordinal logistic regression. RESULTS:In univariable analyses, Hurley stage 3, higher body mass index, diabetes, and lower hemoglobin were associated with lower adalimumab durability. In the multivariable model, Hurley stage 3 remained independently associated with less favorable durability (adjusted odds ratio 0.37, 95% confidence interval 0.17-0.81). Comorbid psoriasis was not significantly associated with durability (adjusted odds ratio 2.84, 95% confidence interval 0.96-8.39). Baseline laboratory parameters, including leukocyte and monocyte counts and albumin, did not predict outcome. Age at disease onset, disease duration, and other demographic characteristics were also not associated with durability. CONCLUSION:Hurley stage 3 was independently associated with lower adalimumab durability, while routinely available laboratory measures did not identify additional predictors of long-term treatment outcome.

This cohort study examines the association of a change in International Hidradenitis Suppurativa Severity Score System score with intravenously and subcutaneously administered golimumab in patients with moderate to severe hidradenitis suppurativa.

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.

QuestionCan investigators agree on morphological definitions and methods of assessment for lesions in clinical trials for hidradenitis suppurativa (HS)?FindingThrough a modified Delphi process involving expert dermatologists, consensus was achieved on 11 morphologic lesion definitions and on 16 of 18 statements guiding standardized HS lesion assessments.MeaningConsensus on detailed morphologic definitions to support classification of HS lesions and guidance that standardizes assessment of these lesions can be implemented in study protocols and investigator trainings with the goal of improving accuracy and reliability of investigator ratings in clinical trials for HS. This consensus statement establishes consensus-based morphological definitions of hidradenitis suppurativa (HS) lesions and guidance statements that standardize investigator lesion assessments for implementation in clinical trials. ImportanceAccurate 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.ObjectiveTo establish consensus-based morphological definitions of HS lesions and guidance statements that standardize investigator lesion assessments for implementation in clinical trials.Evidence ReviewHealth 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.FindingsResponse 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 RelevanceCommon 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.

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.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder marked by dysregulated TNF-α signaling and aberrant adaptive immune responses, yet the role of humoral autoimmunity in disease pathogenesis remains incompletely understood. Although autoantibodies have been reported in HS, their prevalence, specificity, and clinical relevance, particularly in relation to clinical features and biologic therapy, are not well defined. This study aimed to characterize lesional IgG autoantibody profiles in HS and evaluate their associations with clinical features, comorbidities, and biologic treatment status. Skin biopsy specimens from 20 patients with HS and 5 control subjects were analyzed for IgG autoantibodies, and findings were correlated with clinical features. Patients with HS demonstrated significantly elevated lesional IgG autoantibody levels, with greater abundance observed in chronic disease stages. Higher autoantibody levels were more prevalent among Black patients and correlated with disease severity (Hurley stage, hidradenitis suppurativa lesion, area, and severity index), lesion type (sinus tracts, scarring), comorbidities including asthma, acne, and diabetes, and clinical factors such as pain severity and smoking status. Samples from patients receiving adalimumab showed lower autoantibody levels, whereas no consistent pattern was observed with infliximab. These findings identify lesional IgG autoantibodies as a feature of HS and support a role for humoral autoimmunity in HS pathobiology, warranting longitudinal investigation.