End-of-Dose Effect as a Guide for Biologic Optimization in Hidradenitis Suppurativa

Importance Up to one-half of patients treated with licensed biologics for hidradenitis suppurativa (HS) achieve only a partial response, yet no consensus exists on subsequent management. Dose intensification and long-term antibiotic addition are used in routine practice, but real-world data on their effectiveness remain limited. Objective To evaluate a response-pattern–guided biologic optimization framework in HS partial responders. Design, Setting, and Participants This was a single-center retrospective cohort study conducted at a tertiary dermatology center in France from January 2022 to March 2025. Patients with HS and insufficient response to anti-tumor necrosis factor-α or anti–interleukin 17 (IL-17) therapy (at least 4 flares per year despite at least 3 months of standard-dose biologic) were included. Data were analyzed from August to October 2025. Exposures Patients with an end-of-dose effect (recurrence of disease activity before the next injection) underwent dose intensification (optimization group; n = 52); those without received antibiotic addition (combination group; n = 50) per a prespecified algorithm. Main Outcomes and Measures The primary outcome was International Hidradenitis Suppurativa Severity Score System (IHS4) response (at least 3-point reduction) at 3 to 5 months; secondary outcomes included IHS4 score reduction of 55% or more, IHS4 stage shift, pain numeric rating scale, flare-frequency and flare-duration responses, and patient-reported global improvement. Inverse probability of treatment weighting with doubly robust adjustment addressed allocation bias. Results Among 107 included patients, 51 (47.7%) were female and 56 (52.3%) were male; the mean (SD) age was 31.7 (9.5) years and the median (IQR) disease duration was 10 (6-16) years. A total of 52 underwent dose intensification and 50 received antibiotic addition. The mean (SD) IHS4 decreased from 7.0 (4.8) to 3.9 (4.2) at 3 to 5 months ( P < .001), with 50 of 93 (53.8%) reaching IHS4 response, 50 of 99 (50.5%) a 55% or greater reduction in IHS4 score, 52 of 102 (51.0%) flare-frequency response, and 65 of 100 (65.0%) global improvement. An exploratory between-arm comparison showed a nominally significant signal favoring intensification on flare-duration response (odds ratio, 2.56; 95% CI, 1.07-6.11) that did not persist after multiplicity adjustment (adjusted P = .24). Improvement was sustained at 6 to 12 months in 65 patients. Conclusions and Relevance In this cohort of patients with HS who partially responded to biologics, a response-pattern–guided optimization framework was associated with clinically meaningful improvement across all prespecified outcomes. The end-of-dose effect may serve as a candidate phenotyping tool to guide optimization strategy selection, pending prospective confirmation.