Efficacy and Safety of Adalimumab in Conjunction With Surgery in Moderate to Severe Hidradenitis Suppurativa: The SHARPS Randomized Clinical Trial

Abstract

Importance: Surgery is a mainstay in the management of hidradenitis suppurativa (HS). Adalimumab is the first drug approved for HS.

Objective: To investigate the efficacy and safety of adalimumab in combination with wide-excision surgery followed by secondary intention healing.

Design, setting, and participants: The Safety and Efficacy of Adalimumab for Hidradenitis Suppurativa Peri-Surgically (SHARPS) trial was a phase 4, randomized, double-blind, placebo-controlled study of adalimumab in conjunction with surgery. Patients were enrolled in 45 sites across 20 countries from July 18, 2016, to February 2, 2019, with the last patient visit on October 16, 2019. Eligible patients (aged 18-65 years) had moderate to severe HS that required radical surgery in an axillary or inguinal region and had 2 other anatomical regions affected, with 1 or more regions at Hurley stage II or III. Analysis was conducted in November 2019.

Interventions: Patients were randomized 1:1 to receive continuous adalimumab, 40 mg, or placebo during presurgery (12 weeks), perioperative (2 weeks), and postoperative (10 weeks) periods.

Main outcomes and measures: The primary end point was the proportion of patients achieving HS clinical response across all body regions at week 12.

Results: Overall, 103 patients were randomized to adalimumab and 103 to matching placebo. Among all patients, 51% (n = 106) were women, 94% (n = 193) were White, and the mean (SD) age was 37.6 (11.3) years. At week 12, significantly more patients receiving adalimumab (49 of 103 [48%]) vs placebo (35 of 103 [34%]; P = .049) achieved HS clinical response across all body regions (treatment difference, 14% [95% CI, 0%-27%]). Treatment-emergent adverse events were reported in 74 of 103 patients (72%) and 69 of 103 patients (67%) in the adalimumab and placebo groups, respectively. No increased risk of postoperative wound infection, complication, or hemorrhage was observed with adalimumab vs placebo. Two deaths occurred in the adalimumab group; neither was considered as having a reasonable possibility of relationship to study drug.

Conclusions and relevance: Adalimumab was efficacious in conjunction with wide-excision surgery followed by secondary intention healing, with no need to interrupt treatment prior to surgery. These data support further investigation of adalimumab as an adjuvant therapy to surgery in patients with moderate to severe HS.

Trial registration: ClinicalTrials.gov Identifier: NCT02808975.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Bechara received honoraria from AbbVie, Novartis, and Janssen for advisory board and speaker services, and his department received grants from AbbVie, Novartis, UCB, InflaRx, Incyte, and Janssen for his participation as an investigator. Dr Podda reported personal fees from AbbVie and grants from AbbVie paid to Klinikum Darmstadt during the conduct of the study; personal fees and grants paid to Klinikum Darmstadt from Beiersdorf, Bristol Myers Squibb, CSL Behring, Galderma, Janssen-Cilag, Leo Pharma, Novartis, MSD, USB, Boehringer Ingelheim, Eli Lilly and Company, and InflaRx outside the submitted work. Dr Prens received honoraria from AbbVie, Amgen, Celgene, Eli Lilly and Company, Janssen-Cilag, Galderma, InflaRx, Novartis, UCB, Regeneron, and Pfizer for speaker and advisory board services and received investigator-initiated grants (paid to the Erasmus MC) from AbbVie, Celgene, Janssen-Cilag, and UCB. Dr Horváth reported grants from Janssen-Cilag, AbbVie, Novartis, UCB Pharma, and Leo Pharma paid to their institution during the conduct of the study; grants from Solenne BV, Celgene, Akari Therapeutics, Philips, Roche, Regeneron, and Sanofi paid to their institution outside the submitted work; and personal fees from Janssen-Cilag, AbbVie, Novartis Pharma, UCB Pharma, Leo Pharma, Solenne BV, Celgene, Akari Therapeutics, Philips, Roche, Regeneron, and Sanofi paid to their institution. Dr Giamarellos-Bourboulis reported grants from AbbVie for the SHARPS study to the National and Kapodistrian University of Athens during the conduct of the study; grants from Abbott, InflaRx, XBiotech, Astellas Pharma, Axis Shield, Horizon 2020 ImmunoSep, bioMérieux, FrameWork 7 HemoSpec, and Horizon 2020 Marie Curie ITN European Sepsis Academy; personal fees from Abbott, XBiotech, Angelini Pharma, Pfizer, and ThermoFisher outside the submitted work; and honoraria from MSD. Dr Alavi reported grants from AbbVie during the conduct of the study; personal fees from Novartis, Janssen, Kymera Therapeutics, and AbbVie outside the submitted work; and has acted as a consultant, advisor, and/or received research funding from Asana, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Galderma, Genentech, Glenmark, Incyte, InflaRx, Leo Pharma, Novartis, Regeneron, UCB, and Valeant. Dr Szepietowski is an advisory board member of AbbVie, Leo Pharma, Novartis, Pierre Fabre, Menlo Therapeutics, Sienna Biopharmaceuticals, and Trevi; principal investigator for AbbVie, Novartis, Menlo Therapeutics, Trevi, Janssen, Merck, Regeneron, Amgen, Boehringer Ingelheim, Galapagos, Galderma, InflaRx, Kymab, Pfizer, UCB, Helm, and Incyte; speaker for AbbVie, Novartis, Janssen, Eli Lilly, Sanofi Genzyme, Sun Pharma, and Berlin-Chemie Menarini; and reported personal fees from AbbVie during the conduct of the study and outside the submitted work. Dr Kirby reported personal fees from AbbVie, ChemoCentryx, Incyte, Novartis, Janssen, and UCB Pharma outside the submitted work. Dr Geng reported owns AbbVie stock as an employee. Dr Jean reported being a former employee of AbbVie and owns stock or stock options. Dr Jemec reported grants from AbbVie, InflaRx, Novartis, Janssen-Cilag, CSL Behring, Afyx, Regeneron, and Leo Pharma; personal fees from UCB Pharma, Incyte, and ChemoCentryx during the conduct of the study; personal fees from Coloplast, Novartis, and Leo Pharma outside the submitted work; a patent for a probiotic pending; is editor in chief of Dermatology; advisor at Miiskin and Henlez; honoraria from Kymera and VielaBio. Dr Zouboulis reported grants from AbbVie paid to the Dessau Medical Center during the conduct of the study; grants from AbbVie paid to the Dessau Medical Center outside the submitted work; personal fees from AbbVie outside the submitted work; personal consultation/lecture/advisory board honoraria from Almirall, Bayer, Celgene, Galderma, GlaxoSmithKline/Stiefel, Idorsia, Incyte, InflaRx, Janssen, Novartis, Pierre Fabre, PPM Pharma, Regeneron, Sobi, UCB; and fees paid to the Dessau Medical Center for participation at clinical studies from Advanced Oxygen Therapy Inc, AstraZeneca, Galderma, InflaRx, NAOS-Bioderma, Novartis, PPM Pharma, Relaxera, and UCB Pharma.

Figures

Figure 1.. Patient Disposition

HS indicates hidradenitis suppurativa. aPrimary reason for discontinuation given.

Figure 2.. Patients Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Presurgical Visits and Achieving HiSCR-es at All Visits

Patients achieving HiSCR at presurgical visits in the intent-to-treat (ITT) population (A) and in sensitivity analysis (B) and patients achieving HiSCR excluding the surgical site (HiSCR-es) at all visits in the ITT population (C) and in sensitivity analysis (D). Post hoc sensitivity analyses were conducted to exclude the 21 patients with baseline abscess and inflammatory nodule of less than 3 at the hidradenitis suppurativa nonsurgical site (ie, did not meet the key lesion entry criterion of baseline abscess and inflammatory nodule count of ≥3 at hidradenitis suppurativa nonsurgical sites). All panels represent nonresponder imputation analyses. The primary end point was HiSCR at week 12. The first ranked secondary end point was HiSCR-es at week 12 and the second ranked secondary end point was HiSCR-es at week 24. A and B, P values for visits other than week 12 are nominal P values without controlling for overall type I error. C and D, P values for visits other than weeks 12 and 24 are nominal P values without controlling for overall type I error.

Figure 3.. Change From Baseline in Ranked Secondary Surgical End Points at Week 12

Change from baseline in surface area of hidradenitis suppurativa (HS) surgical site (A) and patients requiring less extensive surgery than the surgical plan or no surgery (B). Intent-to-treat (ITT) and post hoc sensitivity analyses are presented for both panels. Post hoc sensitivity analyses were conducted to exclude the 21 patients with baseline abscess and inflammatory nodules less than 3 at the HS nonsurgical site (ie, did not meet the key lesion entry criterion of baseline abscess and inflammatory nodule count of ≥3 at the HS nonsurgical site). Both panels represent an as-observed analysis approach. LS indicates least squares. aA positive percentage change indicates an increase in the actual surgical area at week 13 compared with the planned surgical area at baseline, with few extreme observations (n = 3) of an increase more than 1000%.