Quantifying the natural variation in lesion counts over time in untreated hidradenitis suppurativa: Implications for outcome measures and trial design

BACKGROUND: Hidradenitis suppurativa (HS) demonstrates high placebo response rates in clinical trials, possibly due to the natural variability of the disease. No quantification of variability in lesion counts of untreated disease has been undertaken. OBJECTIVE: To quantify the variability of untreated HS. METHODS: Deidentified individual patient data from the placebo arms of PIONEER studies were analyzed, and measurements of within-subject coefficients of variation were examined. Variability was stratified by disease-associated variables (Hurley stage, BMI, sex, smoking, family history) and body site. RESULTS: Analysis of within-subject coefficients of variation demonstrated that half of the participants had a middle spread [difference between 75(th) and 25(th) percentiles of the subject's abscess and nodule counts] greater than 33% and 40% of their median abscess and nodule counts, and 25% of the subjects had a middle spread greater than 70% and 78% of their median abscess and nodule counts in PIONEER I and II, respectively. Hurley stage 2 participants had significantly greater within-subject variation than Hurley stage 3 patients. Variation was greater in the axillary and groin regions than in other anatomical locations. LIMITATIONS: Limitations include the use of precollected clinical trial data. CONCLUSION: The within-subject variability of the lesion counts in untreated HS was greater than previously appreciated. This has profound effects on outcome measures and the conduct of future clinical trials of HS.