Genetic Variants Associated With Hidradenitis Suppurativa.

Importance: Hidradenitis suppurativa (HS) is a common and severely morbid chronic inflammatory skin disease that is reported to be highly heritable. However, the genetic understanding of HS is insufficient, and limited genome-wide association studies (GWASs) have been performed for HS, which have not identified significant risk loci. Objective: To identify genetic variants associated with HS and to shed light on the underlying genes and genetic mechanisms. Design, Setting, and Participants: This genetic association study recruited 753 patients with HS in the HS Program for Research and Care Excellence (HS ProCARE) at the University of North Carolina Department of Dermatology from August 2018 to July 2021. A GWAS was performed for 720 patients (after quality control) with controls from the Add Health study and then meta-analyzed with 2 large biobanks, UK Biobank (247 cases) and FinnGen (673 cases). Variants at 3 loci were tested for replication in the BioVU biobank (290 cases). Data analysis was performed from September 2021 to December 2022. Main Outcomes and Measures: Main outcome measures are loci identified, with association of P < 1 × 10-8 considered significant. Results: A total of 753 patients were recruited, with 720 included in the analysis. Mean (SD) age at symptom onset was 20.3 (10.57) years and at enrollment was 35.3 (13.52) years; 360 (50.0%) patients were Black, and 575 (79.7%) were female. In a meta-analysis of the 4 studies, 2 HS-associated loci were identified and replicated, with lead variants rs10512572 (P = 2.3 × 10-11) and rs17090189 (P = 2.1 × 10-8) near the SOX9 and KLF5 genes, respectively. Variants at these loci are located in enhancer regulatory elements detected in skin tissue. Conclusions and Relevance: In this genetic association study, common variants associated with HS located near the SOX9 and KLF5 genes were associated with risk of HS. These or other nearby genes may be associated with genetic risk of disease and the development of clinical features, such as cysts, comedones, and inflammatory tunnels, that are unique to HS. New insights into disease pathogenesis related to these genes may help predict disease progression and novel treatment approaches in the future.

Comparing the Effectiveness and Safety Associated With Infliximab vs Infliximab-abda Therapy for Patients With Hidradenitis Suppurativa.

IMPORTANCE: Although limited effective and affordable treatment options exist for hidradenitis suppurativa, recent studies describe the effectiveness of a medical therapy, infliximab, for the treatment of hidradenitis suppurativa. Cost-saving biosimilar alternatives have recently become available, but no data currently exist on their safety and effectiveness. OBJECTIVE: To evaluate the effectiveness of infliximab-abda vs infliximab administration associated with the treatment of hidradenitis suppurativa. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study identified patients treated with infliximab or infliximab-abda between 2016 and 2020 at the dermatology clinic at the University of North Carolina at Chapel Hill. The study population included patients who met the clinical criteria for hidradenitis suppurativa and had received a continuous dose of infliximab or infliximab-abda for at least 10 weeks. In total, 62 potential participants were identified using clinical tracking lists on the electronic medical records, and 34 participants were included in the final analysis. EXPOSURES: Patients who started receiving infliximab or infliximab-abda were clinically tracked for a minimum of 10 weeks using the electronic medical record system, beginning at the time of drug initiation. Patients received loading doses of 10 mg/kg at weeks 0, 2, and 6, and then treatment was continued with a maintenance dose administered every 4 to 8 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome measure was Hidradenitis Suppurativa Clinical Response, defined as at least 50% decrease in inflammatory nodule count without any increase in number of abscesses or draining sinuses. RESULTS: Of 34 participants, 20 comprised the infliximab treatment group (mean [SD] age, 42.2 [13.2] years; 17 women [85%]), and 14 comprised the infliximab-abda treatment group (mean [SD] age, 35.5 [10.9] years; 13 women [93%]). The proportions of patients achieving a Hidradenitis Suppurativa Clinical Response were 71% (10 patients) in the infliximab-abda and 60% (12 patients) in the infliximab treatment group, which were not significantly different (P = .47). CONCLUSIONS AND RELEVANCE: This cohort study found that both infliximab administration and infliximab-abda administration were associated with similar and significant improvement in disease as measured by the Hidradenitis Suppurativa Clinical Response. Infliximab-abda is likely a reasonable treatment option for hidradenitis suppurativa, and further research is warranted.