Hormonal influence on hidradenitis suppurativa: Perspective for clinical trial design

Summary: To explore hormonal influence on hidradenitis suppurativa (HS), a prospective natural history study of 28 women with HS was conducted at Duke University Medical Center. Disease activity at both the early follicular phase and luteal phase of same menstrual cycle was evaluated and subjects also maintained daily diaries that assessed pain, odor, drainage and itching. A statistically significant worsening (median difference [Q1-Q3]) of symptoms was seen during the early follicular phase compared to the luteal phase of the menstrual cycle as evaluated by patient-reported outcomes of Dermatology Life Quality Index (2.0 [1.0-5.5], p=0.011) and Hidradenitis Suppurativa Quality of Life (4.5 [-0.5-9.0], p=0.004). However, physician-reported outcomes (abscess-nodule and draining fistula count, and the International Hidradenitis Suppurativa Severity Score System) did not demonstrate statistically significant changes. Physician measures lack sensitivity to detect changes in lesion size and drainage amount; more objective tools like ultrasound or MRI are needed. Poisson regression (incidence rate ratio, 95% CI) of daily diaries across the menstrual cycle also revealed significant increases in pain (1.26, 1.12-1.44, p<0.001), odor (1.09, 1.02-1.16, p=0.007), itch (1.19, 1.09-1.31, p<0.001), and drainage (1.08, 1.01-1.16, p=0.032) during the early follicular phase compared to the luteal phase. A subgroup analysis of 19 Black women found similar patterns. Our study highlights the importance of incorporating hormonal status at the time of disease assessment in HS clinical trials to ensure accurate analysis for treatment responses given the high placebo response rate in HS clinical trials. Tarannum Jaleel¹, Negar Foolad¹, Jade J. Lewis¹, Beiyu Liu², Cynthia L. Green², Dmitri Kazmin⁶, Jennifer Zhang^{1, 3}, Russell Hall¹, Donald McDonnell⁵, Andrea Coviello⁴ 1. Dermatology, Duke University School of Medicine, Durham, NC, United States. 2. Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, United States. 3. Pathology, Duke University School of Medicine, Durham, NC, United States. 4. Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. 5. Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, United States. 6. Stanford University, Stanford, CA, United States. Clinical Research: Epidemiology and Observational Research