Efficacy of Secukinumab Across Subgroups and Overall Safety in Pediatric Patients with Moderate to Severe Plaque Psoriasis: Week 52 Results from a Phase III Randomized Study

Abstract

Background: The efficacy and safety of biologic treatments for children and adolescents with moderate to severe psoriasis should be examined over a considerable time period and in different subgroups.

Objective: We report the efficacy and safety of secukinumab low dose (LD) and high dose (HD) regimens in pediatric patients with moderate to severe psoriasis for up to Week 52.

Methods: This was a randomized, open-label, parallel-group, multicenter study in patients aged 6 to < 18 years. Patients were randomized in a 1:1 ratio to receive LD (75/75/150 mg; N = 42) or HD (75/150/300 mg; N = 42) subcutaneous secukinumab. At randomization, patients were stratified by weight (< 25, 25 to < 50, ≥ 50 kg) and disease severity (moderate/severe). The study is ongoing; the present analysis included data up to Week 52 collected from August 29, 2018 (first patient first visit) to May 28, 2020 (last patient last visit for Week 52). Efficacy was measured using Investigator's Global Assessment modified 2011 0/1 (IGA 0/1) and Psoriasis Area Severity Index (PASI) 75/90/100 response. Safety outcomes included assessment of adverse events.

Results: Of the 84 enrolled patients, 78 (92.9%) completed 52 weeks of treatment. Overall, response rates for PASI 75 and IGA 0/1 were similar between the LD (92.8/88.9%) and HD (93.3/84.7%) groups at Week 52. In the LD and HD groups, PASI 90/100 responses at Week 52 were 78.7/53.5% and 84.7/70.0%, respectively. The proportions of IGA 0/1 and PASI 75/90 responders were comparable for the age, body weight, and disease severity subgroups in the secukinumab LD and HD groups. Mean absolute PASI change from baseline at week 52 was - 17.3 ± standard deviation 5.0 and - 18.2 ± 7.0, a percentage change of - 94.3 and - 94.5% for the LD and HD groups, respectively. More than 70% of evaluable patients achieved Children's Dermatology Life Quality Index 0/1 at Week 52 (LD 70.7%; HD 70.3%). The safety profile was consistent with that in adults, with no new safety signals for either secukinumab dosing regimen.

Conclusion: A high proportion of pediatric patients with psoriasis responded to both dosing regimens of secukinumab and maintained clinical responses through 52 weeks of treatment. No clinical difference was observed in the efficacy of secukinumab across the pediatric subgroups. Safety events were consistent with the established safety profile of secukinumab.

Trial registration: ClinicalTrials.gov: NCT03668613.

Conflict of interest statement

N. Magnolo has been a principal investigator in studies performed by AbbVie, Almirall, Asana, Boehringer Ingelheim, BMS, Celgene, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Genentech, Incyte, Janssen, Kyowa Kirin, LEO Pharma, Novartis, MSD, Pfizer, Regeneron, Sun Pharma, and UCB and is a consultant or speaker for AbbVie, Almirall, Boehringer Ingelheim, Eli Lilly, LEO Pharma, Novartis, Pfizer, and UCB. K. Kingo has received fees for serving as an investigator in studies sponsored by Celgene, Merck, Mitsubishi Tanabe Pharma, Novartis, Regeneron Pharmaceuticals, and Sandoz. V. Laquer is an investigator for AbbVie, Amgen, Biofrontera, Cara Therapeutics, Celgene, ChemoCentryx, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Kiniksa, LEO Pharma, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB. J. Browning is an investigator for Amryt, Brickell Biotech, Celgene, ChemoCentryx, Eli Lilly, Incyte, Lenus, LEO Pharma, Mayne, Novartis, Pfizer, Regeneron, and Valeant; a consultant for Dermavant and LEO Pharma; and a speaker for Dermira, Regeneron, and Pfizer. JC. Szepietowski is an advisory board member for AbbVie, LEO Pharma, Novartis, Pierre Fabre, Menlo Theraputics, Sienna Biopharmaceuticans, and Trevi; a principal investigator for AbbVie, Novartis, Menlo Therapeutics, Trevi, Janssen, Merck, Regeneron, Amgen, Boehringer Ingelheim, Galapagos, Galderma, InflaRX, Kymab Ltd., Pfizer, UCB, Helm, and Incyte; and a speaker for AbbVie, Novartis, Janssen, Eli Lilly, Sanofi-Genzyme, Sunfarm, and Berlin-Chemie Mennarini. A. Reich is a principal investigator or subinvestigator in clinical trials sponsored by AbbVie, Drug Delivery Solutions Ltd, Galderma, Genentech, Janssen, Kymab Ltd, LEO Pharma, Menlo Therapeutics, MetrioPharm AG, MSD, Novartis, Pfizer, and Trevi Therapeutics and a consultant or speaker for AbbVie, Bioderma, Celgene, Chema-Elektromet, Eli Lilly, Galderma, Janssen, LEO Pharma, Medac, Menlo Therapeutics, Novartis, Pierre Fabre, Sandoz, and Trevi Therapeutics. D. Keefe and W. Bao are employees of Novartis Pharmaceuticals Corporation. P. Papanastasiou, P. Forrer and M. Patekar are employees of Novartis Pharma AG.

© 2022. The Author(s).

Figures

Fig. 1

Patient disposition up to Week 52. *One patient discontinued because of alanine aminotransferase and aspartate aminotransferase elevation and another patient because of hemorrhagic diarrhea

Fig. 2

PASI 75/90/100a and IGA mod 2011 0/1 responses up to Week 52. a Low-dose secukinumab (N = 42), b high-dose secukinumab (N = 42). Multiple imputation method was used to impute missing values. IGA mod 2011 0/1 Investigator’s Global Assessment modified 2011, N total number of patients, PASI 75/90/100 percentage of patients who achieved a ≥ 75%, ≥ 90%, or 100% reduction in Psoriasis Area and Severity Index score from baseline. aPASI 75/90/100, percentage of patients who achieved a ≥ 75%/≥ 90%/100% reduction in PASI score from BL Multiple imputation method was used to impute missing values

Fig. 3

Change in PASI score from baseline (mean ± standard deviation) up to Week 52 (last observed carried forward; full analysis set). a Absolute change, b percentage change. N total number of patients, PASI Psoriasis Area and Severity Index, SEC secukinumab

Fig. 4

Percentage of patients with CDLQI 0/1a. Response through Week 52 (last observation carried forward; full analysis set). a0/1, no impairment in patient’s quality of life. CDLQI Children’s Dermatology Life Quality Index; m number of patients evaluable, n number of patients with response, SEC secukinumab