Efficacy and Safety of Ixekizumab in a Phase III, Randomized, Double-Blind, Placebo-Controlled Study in Paediatric Patients With Moderate-to-Severe Plaque Psoriasis (IXORA-PEDS)

Unless otherwise specified, data are presented as n (%). Values are reported as observed. Unless otherwise indicated, there were no missing values in the baseline characteristics. BMI, body mass index; BSA, body surface area; CDLQI, Children's Dermatology Life Quality Index; DLQI, Dermatology Life Quality Index; IXE, ixekizumab; NAPSI, Nail Psoriasis Severity Index; NRS, numerical rating scale; PASI, Psoriasis Area and Severity Index; PatGA, Patient's Global Assessment of Disease Severity; PPASI, Palmoplantar Psoriasis Area and Severity Index; PSSI, Psoriasis Scalp Severity Index; Q4W, every 4 weeks; sPGA, static Physician's Global Assessment. ^aNumber of patients with nonmissing values: placebo, n = 53; IXE Q4W, n = 114. ^bAssessed for patients with nail psoriasis at baseline (as reported by the investigator). Number of patients with non-missing values: placebo, n = 13; IXE Q4W, n = 34. ^cAssessed for patients with scalp psoriasis at baseline (as reported by the investigator). Number of patients with non-missing values: placebo, n = 50; IXE Q4W, n = 103. ^dAssessed for patients with palmoplantar psoriasis at baseline (as reported by the investigator). Number of patients with non-missing values: placebo, n = 9; IXE Q4W, n = 18. ^eAssessed in patients 6–16 years of age. Number of patients with nonmissing values: placebo, n = 48; IXE Q4W, n = 86. ^fAssessed in patients ≥ 17 years of age. Number of patients with nonmissing values: placebo, n = 6; IXE Q4W, n = 26.

Unless otherwise specified, values are presented as the number of responders (%). Categorical outcomes: Fisher's exact test with nonresponder imputation for handling missing data. Continuous outcomes: mixed model for repeated-measures analysis. Type III tests for least-squares means (LSMs) was used for treatment group comparisons. CDLQI, Children's Dermatology Life Quality Index; CFB, change from baseline; DLQI, Dermatology Life Quality Index; IXE, ixekizumab; NAPSI, Nail Psoriasis Severity Index; NRS, numerical rating scale; PASI, Psoriasis Area and Severity Index; PatGA, Patient's Global Assessment of Disease Severity; PPASI, Palmoplantar Psoriasis Area and Severity Index; PSSI, Psoriasis Scalp Severity Index; Q4W, every 4 weeks; sPGA, static Physician's Global Assessment. ^aAssessed for patients with baseline itch NRS ≥ 4. Placebo, n = 40; IXE Q4W, n = 83. ^bCDLQI was assessed for patients 6–16 years of age. DLQI was assessed for patients ≥ 17 years of age. ^cAssessed for patients with baseline NAPSI > 0. Placebo, n = 12; IXE Q4W, n = 34. ^dAssessed for patients with baseline PSSI > 0. Placebo, n = 50; IXE Q4W, n = 102. ^eAssessed for patients with baseline PPASI > 0. Placebo, n = 9; IXE Q4W, n = 17. ^fAssessed for patients with genital psoriasis at baseline.

Values are presented as the number of responders (%). Fisher's exact test with nonresponder imputation was used to handle missing data. CI, confidence interval; ETN, etanercept; IXE, ixekizumab; PASI, Psoriasis Area and Severity Index; Q4W, every 4 weeks; sPGA, static Physician's Global Assessment.

The data are presented as n (%). (Except patient-years of exposure.) IBD, inflammatory bowel disease; IXE, ixekizumab; Q4W, every 4 weeks. ^aIncludes all randomized patients who took at least one dose of double-blind study treatment according to the treatment to which they were assigned. ^bIncludes all patients who received at least one dose of IXE, including those randomized to placebo or etanercept at week 0 who received open-label IXE Q4W during the maintenance period.

Authors and Disclosures

A.S. Paller¹, M.M.B. Seyger², G. Alejandro Magariños³, J. Bagel⁴, A. Pinter⁵, J. Cather⁶, S. Keller⁷, C. Rodriguez Capriles⁷, R. Gontijo Lima⁷, G. Gallo⁷, C.A. Little⁷, E. Edson-Heredia⁷, L. Li⁷, W. Xu⁷ and K. Papp⁸ on behalf of the IXORA-PEDS study group

¹Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
²Department of Dermatology, Radboud University Medical Center, Nijmegen, the Netherlands
³Psoriahue, Buenos Aires, Argentina
⁴Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ, USA
⁵Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Frankfurt am Main, Germany
⁶Mindful Dermatology and Modern Research Associates, Dallas, TX, USA
⁷Eli Lilly and Company, Indianapolis, IN, USA
⁸K Papp Clinical Research and Probity Medical Research, Waterloo, ON, Canada

Correspondence
Amy Paller Email: apaller@northwestern.edu

Conflicts of interest statements are listed in Appendix 1.

Appendix 1

Conflicts of interest. A.S.P. has been an investigator for AbbVie, Eli Lilly and Company, Exicure, Galderma, Incyte, Janssen, Novartis, Palvella and Regeneron; and has been a consultant with honoraria from AbbVie, Almirall, Asana, Boehringer Ingelheim, Castle Creek, Dermira, Eli Lilly and Company, Exicure, Forte, Galderma, Janssen, LEO Pharma, LifeMax, MEDACorp, Novartis, Pierre Fabre, Regeneron, Sanofi Genzyme and Sol-Gel. M.M.B.S. has received grants from or has been involved in clinical trials with AbbVie, Celgene, Eli Lilly and Company, Janssen, LEO Pharma and Pfizer; and has served as a consultant for AbbVie, Eli Lilly and Company, Janssen, LEO Pharma and Pfizer; fees were paid directly to the institution. G.A.M. has received honoraria and/or grants as a speaker, advisor or investigator for AbbVie, Amgen, Biogen, Boehringer Ingelheim, Eli Lilly and Company, Janssen Cilag, Novartis, Pfizer and Sanofi Genzyme. J.B. has been a speaker, consultant or investigator for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, LEO Pharma, Novartis, Ortho Dermatologics and Sun Pharma. A.P. has been an investigator, speaker and/or advisor for AbbVie, Almirall-Hermal, Amgen, Biogen Idec, Biontec, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Galderma, GSK, Hexal, Janssen, LEO Pharma, MC2, Medac, Merck Serono, Mitsubishi, MSD, Novartis, Pascoe, Pfizer, Tigercat Pharma, Regeneron, Roche, Sandoz Biopharmaceuticals, Sanofi Genzyme, Schering-Plough and UCB Pharma. J.C. has been an investigator, speaker, consultant and/or advisory board member for AbbVie, Amgen, Arena, Brickell Biotech, Bristol Myers Squibb, Celgene, ChemoCentryx, Eli Lilly and Company, Galderma, Janssen, Menlo, Regeneron, Sun Pharma and UCB. S.K., C.R.C., R.G.L., G.G., C.A.L., E.E.H., L.L. and W.X. are employees of and own stock in Eli Lilly and Company. K.P. has received honoraria, grants and/or research funding as a speaker, investigator, advisory board member, data safety monitoring board member and/or consultant for AbbVie, Akros, Amgen, Anacor, Arcutis, Astellas Pharma US, Bausch Health, Baxalta, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Celgene Corporation, Coherus, Dermira, Dow Pharmaceuticals, Eli Lilly and Company, Evelo, Galapagos, Galderma, Genentech, Gilead, GSK, Janssen, Kyowa Hakko Kirin Pharma, LEO Pharma, MedImmune, Meiji Seika Pharma, Merck (MSD), Merck Serono, Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Roche Laboratories, Sanofi Genzyme, Takeda Pharmaceuticals and UCB.

Appendix 2

Author contributions. A.S.P. contributed to the study design, data acquisition, data interpretation and critical revision of the manuscript. M.M.B.S. and K.P. contributed to data acquisition, data interpretation and critical revision of the manuscript. G.A.M. contributed to the study design, data interpretation and critical revision of the manuscript. J.B. and A.P. contributed to data analysis, data interpretation and critical revision of the manuscript. J.C., G.G., C.A.L. and E.E.H. contributed to data interpretation and critical revision of the manuscript. S.K., C.R.C. and R.G.L. contributed to the study design, data interpretation and critical revision of the manuscript. L.L. and W.X. contributed to the study design, data analysis, data interpretation and critical revision of the manuscript. All authors provided approval of the final manuscript for submission and publication.

Sidebar 1

What is Already Known About This Topic?

• Paediatric psoriasis affects approximately 1% of children and can negatively impact health-related quality of life.

• Treatment options for paediatric psoriasis are typically limited to off-label treatments and approved systemic biologics.

• Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for moderate-to-severe plaque psoriasis in adults and was recently approved by the US Food and Drug Administration for moderate-to-severe paediatric psoriasis.

Sidebar 2

What Does This Study Add?

1. Ixekizumab resulted in rapid and statistically significant improvements over placebo in skin involvement, itch and health-related quality of life, which persisted through 48 weeks of treatment in paediatric patients with moderate-to-severe plaque psoriasis.

2. The safety profile of ixekizumab was generally consistent with that seen in adults.

3. Ixekizumab may be an additional potential therapeutic option and an additional class of biologic therapy (interleukin-17A antagonist) for the treatment of moderate-to-severe paediatric psoriasis.