Secukinumab in moderate-to-severe hidradenitis suppurativa (SUNSHINE and SUNRISE): week 16 and week 52 results of two identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials.

BACKGROUND

Few therapeutic options are available for patients with moderate-to-severe hidradenitis suppurativa. We aimed to assess the efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa in two randomised trials.

METHODS

SUNSHINE and SUNRISE were identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials done in 219 primary sites in 40 countries. Patients aged 18 years old or older with the capacity to provide written informed consent and with moderate-to-severe hidradenitis suppurativa (defined as a total of ≥5 inflammatory lesions affecting ≥2 distinct anatomical areas) for at least 1 year were eligible for inclusion. Included patients also agreed to daily use of topical over-the-counter antiseptics on the areas affected by hidradenitis suppurativa lesions while on study treatment. Patients were excluded if they had 20 or more fistulae at baseline, had ongoing active conditions requiring treatment with prohibited medication (eg, systemic biological immunomodulating treatment, live vaccines, or other investigational treatments), or met other exclusion criteria. In both trials, patients were randomly assigned (1:1:1) by means of interactive response technology to receive subcutaneous secukinumab 300 mg every 2 weeks, subcutaneous secukinumab 300 mg every 4 weeks, or subcutaneous placebo all via a 2 mL prefilled syringe in a double-dummy method as per treatment assignment. The primary endpoint was the proportion of patients with a hidradenitis suppurativa clinical response, defined as a decrease in abscess and inflammatory nodule count by 50% or more with no increase in the number of abscesses or in the number of draining fistulae compared with baseline, at week 16, assessed in the overall population. Hidradenitis suppurativa clinical response was calculated based on the number of abscesses, inflammatory nodules, draining fistulae, total fistulae, and other lesions in the hidradenitis suppurativa affected areas. Safety was assessed by evaluating the presence of adverse events and serious adverse events according to common terminology criteria for adverse events, which were coded using Medical Dictionary for Regulatory Activities terminology. Both the SUNSHINE, NCT03713619, and SUNRISE, NCT03713632, trials are registered with ClinicalTrials.gov.

FINDINGS

Between Jan 31, 2019, and June 7, 2021, 676 patients were screened for inclusion in the SUNSHINE trial, of whom 541 (80%; 304 [56%] women and 237 [44%] men; mean age 36·1 years [SD 11·7]) were included in the analysis (181 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 180 [33%] in the placebo group). Between the same recruitment dates, 687 patients were screened for inclusion in the SUNRISE trial, of whom 543 (79%; 306 [56%] women and 237 [44%] men; mean age 36·3 [11·4] years) were included in the analysis (180 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 183 [34%] in the placebo group). In the SUNSHINE trial, significantly more patients in the secukinumab every 2 weeks group had a hidradenitis suppurativa clinical response (rounded average number of patients with response in 100 imputations, 81·5 [45%] of 181 patients) compared with the placebo group (60·7 [34%] of 180 patients; odds ratio 1·8 [95% CI 1·1-2·7]; p=0·0070). However, there was no significant difference between the number of patients in the secukinumab every 4 weeks group (75·2 [42%] of 180 patients) and the placebo group (1·5 [1·0-2·3]; p=0·042). Compared with the placebo group (57·1 [31%] of 183 patients), significantly more patients in the secukinumab every 2 weeks group (76·2 [42%] of 180 patients; 1·6 [1·1-2·6]; p=0·015) and the secukinumab every 4 weeks group (83·1 [46%] of 180 patients; 1·9 [1·2-3·0]; p=0·0022) had a hidradenitis suppurativa clinical response in the SUNRISE trial. Patient responses were sustained up to the end of the trials at week 52. The most common adverse event by preferred term up to week 16 was headache in both the SUNSHINE (17 [9%] patients in the secukinumab every 2 weeks group, 20 [11%] in the secukinumab every 4 weeks group, and 14 [8%] in the placebo group) and SUNRISE (21 [12%] patients in the secukinumab every 2 weeks group, 17 [9%] in the secukinumab every 4 weeks group, and 15 [8%] in the placebo group) trials. No study-related deaths were reported up to week 16. The safety profile of secukinumab in both trials was consistent with that previously reported, with no new or unexpected safety findings detected.

INTERPRETATION

When given every 2 weeks, secukinumab was clinically effective at rapidly improving signs and symptoms of hidradenitis suppurativa with a favourable safety profile and with sustained response up to 52 weeks of treatment.

FUNDING

Novartis Pharma.

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests ABK reports grants from AbbVie, Anapyts Bio, Aristea, Bristol Myers Squibb, ChemoCentryx, Eli Lilly, Incyte, Janssen, Moonlake, Novartis, Pfizer, UCB, and Sonoma Bio and fellowship funding from AbbVie and Janssen paid to her institution; royalties from BIDMC; consulting fees from AbbVie, Alumis, Bayer, Bristol Myers Squibb, Boehringer-Ingelheim, Eli Lilly, FIDE, Novartis, Moonlake, Janssen, Pfizer, Priovant, Sonoma Bio, Sanofi, Target RWE, UCB, and Ventyx; stock in Ventyx; serving on advisory boards for Target RWE; serving as an advisory council member to the National Institute of Health Director; and serves on the board of directors of Almirall. GBEJ reports grants from AbbVie, Boehringer-Ingelheim, CSL Behring, Regeneron, InflaRx, Novartis, LEO Foundation, and UCB, paid to their institution, and honoraria for advisory board meetings from Coloplast, Union Therapeutics, Toosonix, Boehringer-Ingelheim, Kymera, Sanofi, Viela Bio, ChemoCentryx, LEO Pharma, Afyx, Incyte, InflaRx, Janssen Cilag, Novartis, and UCB. AA reports consulting fees from AbbVie, Boehringer-Ingelheim, InflaRx, and UCB, paid to their institution, and consulting fees from Novartis, AbbVie, and Boehringer-Ingelheim. ZR reports consulting fees and honoraria from AbbVie, Amgen, Janssen-Cilag, Novartis, UCB, Sanofi; consulting fees from Celltrion; personal fees for attending meetings or for travel from AbbVie, Janssen-Cilag, Novartis, UCB, and Sanofi; and payment for expert testimony from AbbVie, Amgen, Celltrion, Janssen-Cilag, Novartis, and UCB. ABG reports research and educational grants from AnaptysBio, Janssen, Novartis, Ortho Dermatologics, Sun Pharma, BMS, and UCB Pharma, paid to their institution; consulting fees from Amgen, AnaptysBio, Avotres Therapeutics, Boehringer-Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and DiCE Therapeutics; honoraria as an advisory board member, or non-promotional speaker from Amgen, AnaptysBio, Avotres Therapeutics, Boehringer-Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, and UCB Pharma; is a president of International Dermatology Outcome Measures; and holds stock options in XBiotech, for work on a rheumatoid arthritis project. FGB reports consulting fees from AbbVie, Novartis, and UCB; honoraria and support for attending meetings or travel from AbbVie, Janssen Cilag, Novartis, and UCB; and served on a Data Safety Monitoring Board or Advisory Board for AbbVie, Boehringer-Ingelheim, Janssen Cilag, Novartis, UCB, Incyte, and Moonlake. CP reports consulting fees from Almirall, AbbVie, Amgen, BMS, Boehringer-Ingelheim, Celgene, GSK, Janssen, LEO Pharma, Eli Lilly, Merck, Novartis, Pfizer, Sanofi, and UCB and served on a Data Safety Monitoring Board or Advisory Board for IQVIA. EJGB reports grants from Horizon 2020 ImmunoSep and RISKinCOVID, Horizon Health EPIC-CROWN-2, Sobi, bioMérieux, MSD, Abbott, Novartis, UCB, and AbbVie, paid to their institution, and consulting fees from Sobi, Pfizer, Abbott, ThermoFisher, and Menarini. APV reports consulting fees from Janssen-Cilag; payment or honoraria from AbbVie, Almirall, BMS, Janssen-Cilag, Leo Pharma, Eli Lilly, MSD, Novartis, and UCB; and support for attending meetings or travel from Janssen-Cilag and UCB. AS reports consulting fees from Regeneron, Novartis, and AbbVie, paid to their institution; payment or honoraria from AbbVie, Novartis, Regeneron, Sanofi; support for attending meetings or travel from AbbVie, Janssen-Cilag, Novartis, and Sanofi; and fees for participation on a Data Safety Monitoring Board or Advisory Board from AbbVie, Novartis, and Sanofi. FR reports grants from ALK-Abelló, Allergopharma, Blueprint Medicines, Mylan, Novartis, and ThermoFisher; served on a Data Safety Monitoring Board or Advisory Board for ALK-Abelló, Boehringer-Ingelheim, Blueprint Medicines, Leo Pharma, and UCB; and is an active member of the German Association of Allergy and Clinical Immunology. AR and his institution received grants from AbbVie, Alvotech, Amgen, AnaptysBio, Argenx, Biothera, Bristol Myers Squibb, Celgene, Celltrion, Dermira, Galderma, Inflarx, Janssen, Kiniksa, Kymab, Leo Pharma, Novartis, Pfizer, Trevi Therapeutics, and UCB; payment or honoraria from Chema Rzeszow, Eli Lilly, Leo Pharma, Novartis, Sandoz, and Takeda; and served on a Data Safety Monitoring Board or Advisory Board for AbbVie, Galderma, Sandoz, and Sanofi Aventis. IL reports payment or honoraria from Novartis and support for attending meetings or travel from Sanofi. TP reporfts grants from Almirall, Incyte, and Pfizer, paid to their institution, and consulting fees from AbbVie, Almirall, Bristol Myers Squibb, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Novartis, and UCB. AM reports consulting fees from AbbVie, Boehringer-Ingelheim, Jansen, Eli Lilly, Novartis, Novo Nordisk, Sandoz, and UCB; payment for expert testimony or honoraria from AbbVie, Boehringer-Ingelheim, Jansen, Eli Lilly, Novartis, Novo Nordisk, Sandoz, and UCB; and support for attending meetings or travel from AbbVie, Novartis, Jansen, and UCB. PM-B reports consulting fees from AbbVie, Almirall, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, and Sanofi; payment or honoraria from AbbVie, Almirall, Janssen, LEO Pharma, Eli Lilly, Novartis, Organon, Pfizer, Sanofi, and Viatris; support for attending meetings or travel from AbbVie, Almirall, Janssen, LEO Pharma, Eli Lilly, Novartis, and Sanofi; and served on a Data Safety Monitoring Board or Advisory Board for AbbVie, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, and Sanofi. GK reports consulting fees from Bayer; payment or honoraria from AbbVie, Abbott, Actelion Pharmaceuticals, Amgen, Basilea Pharmaceutica, Biogen IDEC, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Hexal, Janssen-Cilag, LEO Pharma, Eli Lilly, MSD, Mylan, Novartis, Parexel, Pfizer, and UCB; support for attending meetings or travel from AbbVie, Abbott, Amgen, Basilea Pharmaceutica, Celgene, Janssen-Cilag, LEO Pharma, MSD, Novartis, Pfizer, Sanofi, and UCB; and served on a Data Safety Monitoring Board or Advisory Board for AbbVie, Abbott, Amgen, Basilea, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Janssen-Cilag, LEO Pharma, Eli Lilly, Novartis, and UCB. P-AB reports consulting fees from Novartis, AbbVie, Pfizer, and UCB pharma; payment or honoraria from Novartis and AbbVie; support for attending meetings or travel from Novartis; and served on a Data Safety Monitoring Board or Advisory Board for Novartis. MBW, ALM, XW, LU, AP, DK, RM, CF, LC, MV, SR, and EM are employees of Novartis and hold company stock. RS is Director and Founder of Samson Medical, has participated in pharmaceutical advisory boards for Eli Lilly and Company, Pfizer, and Leo Pharmaceutical, has participated in speaker bureaus for AbbVie, Novartis, and Pfizer, and has acted as a principal investigator in clinical trials for AbbVie, Aerotech, Akesobio, Amgen, Arcutis, Arena, Ascend AstraZeneca, Bayer, Biotherapeutics Boehringer-Ingelheim, Bristol-Myer Squibb, Celgene, Coherus BioSciences, Connect, Demira, Eli Lilly, Galderma, GlaxoSmithKline, F Hoffman–La Roche, Janssen, MedImmune, Merck, Merck Sharpe & Dohme, Novartis, Oncobiologics, Pfizer, Principia, Regeneron, Roche, Reistone Biopharma, Samson Clinical, Sanofi-Genzyme, Sun Pharma UCB, Valeant, and Zai Labs. RS is President of the Australasian Hair and Wool Research Society, and Vice President of the International Society of Dermatology and The International Academy of Dermatology. LPR declares no competing interests.