PMID- 35416908 OWN - NLM STAT- MEDLINE DCOM- 20220520 LR - 20221019 IS - 2168-6084 (Electronic) IS - 2168-6068 (Print) IS - 2168-6068 (Linking) VI - 158 IP - 5 DP - 2022 May 1 TI - Long-term Efficacy and Safety of Up to 108 Weeks of Ixekizumab in Pediatric Patients With Moderate to Severe Plaque Psoriasis: The IXORA-PEDS Randomized Clinical Trial. PG - 533-541 LID - 10.1001/jamadermatol.2022.0655 [doi] AB - IMPORTANCE: About 1% of children and adolescents worldwide are affected by plaque psoriasis. OBJECTIVE: To evaluate the long-term efficacy and safety of ixekizumab for pediatric patients with moderate to severe psoriasis. DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial (IXORA-PEDS) evaluated pediatric patients with plaque psoriasis. Participants were aged 6 years to younger than 18 years; had moderate to severe psoriasis, which was defined as Psoriasis Area and Severity Index (PASI) of 12 or higher, static Physician's Global Assessment (sPGA) score of 3 or higher, and psoriasis-affected body surface area of 10% or greater at screening and baseline; were candidates for phototherapy or systemic therapy; or had psoriasis that was not adequately controlled by topical therapies. Data analysis, which followed the intention-to-treat principle, was conducted from May to October 2021. INTERVENTIONS: Pediatric patients were randomized 2:1 to receive either a weight-based dose of ixekizumab every 4 weeks or placebo. After a 12-week placebo-controlled period, patients entered a 48-week, open-label ixekizumab maintenance period (weeks 12-60), followed by an extension period that lasted through 108 weeks. A substudy evaluated the randomized withdrawal of ixekizumab after week 60. MAIN OUTCOMES AND MEASURES: Efficacy outcomes at week 108 included the percentage of patients achieving 75% (PASI 75), 90% (PASI 90), or 100% (PASI 100) improvement from baseline; an sPGA score of 0 or 1 or score of 0; and improvement of 4 points or higher from baseline in the Itch Numeric Rating Scale. Safety outcomes included assessments of adverse events (AEs), including treatment-emergent AEs, serious AEs, and AEs of special interest, as well as improvement from baseline in a range of challenging body areas. Missing data for categorical outcomes were imputed using modified nonresponder imputation. RESULTS: A total of 171 patients (mean [SD] age, 13.5 [3.04] years; 99 female children [57.9%]) were randomized to either ixekizumab (n = 115) or placebo (n = 56). Of 166 patients who entered the maintenance period, 139 (83.7%) completed week 108 of the trial. Primary and gated secondary end points were sustained through week 108, with patients achieving PASI 75 (91.7% [n = 86]), PASI 90 (79.0% [n = 74]), PASI 100 (55.1% [n = 52]), sPGA 0 or 1 (78.3% [n = 74]), and sPGA 0 (52.4% [n = 49]). Fifty-five patients (78.5%) reported an Itch Numeric Rating Scale improvement of 4 points or higher. In patients who received ixekizumab, at week 108, clearance of nail psoriasis was reported in 68.1% (n = 28), clearance of palmoplantar psoriasis was reported in 90.0% (n = 10), clearance of scalp psoriasis was reported in 76.2% (n = 83), and clearance of genital psoriasis was reported in 87.5% (n = 24). There were no new safety findings during weeks 48 to 108 of the trial, including no new cases of inflammatory bowel disease or candida infection. CONCLUSIONS AND RELEVANCE: Results of this study showed improvements across patient-reported outcomes and objective measures of complete skin clearance of psoriasis among pediatric patients who received ixekizumab, and these response rates were sustained through week 108 of the trial. Safety of ixekizumab was consistent with previously reported findings in this population and the known safety profile of this treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03073200. FAU - Paller, Amy S AU - Paller AS AD - Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. AD - Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois. FAU - Seyger, Marieke M B AU - Seyger MMB AD - Department of Dermatology, Radboud University Medical Center, Nijmegen, the Netherlands. FAU - Magarinos, Gabriel A AU - Magarinos GA AD - Psoriahue, Buenos Aires, Argentina. FAU - Pinter, Andreas AU - Pinter A AD - Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Frankfurt am Main, Germany. FAU - Cather, Jennifer C AU - Cather JC AD - Mindful Dermatology and Modern Research Associates, Dallas, Texas. FAU - Rodriguez-Capriles, Claudia AU - Rodriguez-Capriles C AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Zhu, Danting AU - Zhu D AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Somani, Najwa AU - Somani N AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Garrelts, Alyssa AU - Garrelts A AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Papp, Kim A AU - Papp KA AD - K Papp Clinical Research and Probity Medical Research, Waterloo, Ontario, Canada. CN - IXORA-PEDS Investigators LA - eng SI - ClinicalTrials.gov/NCT03073200 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - United States TA - JAMA Dermatol JT - JAMA dermatology JID - 101589530 RN - 0 (Antibodies, Monoclonal, Humanized) RN - BTY153760O (ixekizumab) SB - IM EIN - JAMA Dermatol. 2022 Aug 17;:null. PMID: 35976631 MH - Adolescent MH - Antibodies, Monoclonal, Humanized/*pharmacology MH - Child MH - Double-Blind Method MH - Female MH - Humans MH - *Psoriasis/drug therapy MH - Severity of Illness Index MH - Treatment Outcome PMC - PMC9008559 COIS- Conflict of Interest Disclosures: Dr Paller reported receiving personal fees for consulting from Eli Lilly, AbbVie, UCB, LEO Pharma, and Exicure outside the submitted work as well as receiving grants to institution as an investigator from Eli Lilly, AbbVie, Janssen, Novartis, and UCB outside the submitted work. Dr Seyger reported receiving grants from Eli Lilly and other funding from Amgen, Janssen, and Novartis outside the submitted work. Dr Magarinos reported receiving personal fees from AbbVie, Biogen, Boehringer, Eli Lilly and Co, Janssen, Novartis, and Pfizer outside the submitted work. Dr Cather reported receiving personal fees for advisory board, speaking, and/or clinical trial from AbbVie, Amgen, Bristol Myers Squibb, Celgene, ChemoCentryx, Galderma, UCB, Janssen, Anaptys, and Eli Lilly outside the submitted work. Dr Somani reported receiving other as an employee and minor shareholder from Eli Lilly during the conduct of the study. Dr Garrelts reported receiving other as an employee and shareholder from Eli Lilly during the conduct of the study and outside the submitted work. Dr Papp reported receiving grants, personal fees, and other as a consultant from Eli Lilly during the conduct of the study as well as receiving grants and other as a consultant from AbbVie, UCB, and Novartis; other as a consultant from Sandoz; grants from Amgen, Arcutis, Avillion, Bausch Health, Dermavant, Incyte, LEO Pharma, Pfizer, and Sun Pharma; and personal fees from Bausch Health, Bristol Myers Squibb, Dermavant, and Novartis outside the submitted work. No other disclosures were reported. FIR - Magarinos, Gabriel A IR - Magarinos GA FIR - Galimberti, Ricardo IR - Galimberti R FIR - Viola, Diego IR - Viola D FIR - Luna, Paula IR - Luna P FIR - Lynde, Charles IR - Lynde C FIR - Marcoux, Danielle IR - Marcoux D FIR - Prajapati, Vimal IR - Prajapati V FIR - Cy, Ajith IR - Cy A FIR - Arenberger, Petr IR - Arenberger P FIR - Polaskova, Stanislava IR - Polaskova S FIR - Buckova, Hans IR - Buckova H FIR - Bartonova, Jirina IR - Bartonova J FIR - Cetkovska, Petra IR - Cetkovska P FIR - Hercogova, Jana IR - Hercogova J FIR - Lacour, Jean-Philippe IR - Lacour JP FIR - Phan, Alice IR - Phan A FIR - Sticherling, Michael IR - Sticherling M FIR - Staubach-Renz, Petra IR - Staubach-Renz P FIR - Simon, Margrit IR - Simon M FIR - Pinter, Andreas IR - Pinter A FIR - Magnolo, Nina IR - Magnolo N FIR - Dosa, Piroska IR - Dosa P FIR - Noll, Judit IR - Noll J FIR - Remenyik, Eva IR - Remenyik E FIR - Kemeny, Lajos IR - Kemeny L FIR - Bakos, Noemi IR - Bakos N FIR - Bernabe Del Rio, Claudia IR - Bernabe Del Rio C FIR - Toledo-Bahena, Mirna IR - Toledo-Bahena M FIR - Gomez Flores, Minerva IR - Gomez Flores M FIR - Barragan Estudillo, Zamira IR - Barragan Estudillo Z FIR - Seyger, Marieke IR - Seyger M FIR - Weglowska, Jolanta IR - Weglowska J FIR - Szymanska, Elzbieta IR - Szymanska E FIR - Kaszuba, Andrzej IR - Kaszuba A FIR - Murashkin, Nikolay IR - Murashkin N FIR - Vicente Villa, Asuncion IR - Vicente Villa A FIR - Laguna, Raul L IR - Laguna RL FIR - Rivera Diaz, Raquel IR - Rivera Diaz R FIR - Bagel, Jerry IR - Bagel J FIR - Browning, John IR - Browning J FIR - Bukhalo, Michael IR - Bukhalo M FIR - Cather, Jennifer IR - Cather J FIR - Cruz Santana, Alma IR - Cruz Santana A FIR - Elewski, Boni IR - Elewski B FIR - Forman, Seth IR - Forman S FIR - Gonzalez-Chavez, Jose IR - Gonzalez-Chavez J FIR - Gottlieb, Scott IR - Gottlieb S FIR - Hake Harris, Holly IR - Hake Harris H FIR - Kaffenberger, Jessica IR - Kaffenberger J FIR - Kwong, Pearl IR - Kwong P FIR - Leitenberger, Sabre IR - Leitenberger S FIR - Lugo-Somolinos, Aida IR - Lugo-Somolinos A FIR - Kirkorian, Anna IR - Kirkorian A FIR - Martin, Kari IR - Martin K FIR - Paller, Amy IR - Paller A FIR - Pariser, David IR - Pariser D FIR - Rich, Phoebe IR - Rich P FIR - Rosenblatt, Adena IR - Rosenblatt A FIR - Seminario-Vidal, Lucia IR - Seminario-Vidal L FIR - Siegfried, Elaine IR - Siegfried E FIR - Travers, Jeffrey IR - Travers J FIR - Vendrell-Benito, Pedro IR - Vendrell-Benito P FIR - Weisman, Jamie IR - Weisman J FIR - Wine Lee, Lara IR - Wine Lee L FIR - Zook, Matthew IR - Zook M FIR - Sanches-Rivera, Samuel IR - Sanches-Rivera S FIR - Laquer, Vivian IR - Laquer V EDAT- 2022/04/14 06:00 MHDA- 2022/05/21 06:00 PMCR- 2022/04/13 CRDT- 2022/04/13 12:14 PHST- 2022/04/14 06:00 [pubmed] PHST- 2022/05/21 06:00 [medline] PHST- 2022/04/13 12:14 [entrez] PHST- 2022/04/13 00:00 [pmc-release] AID - 2790783 [pii] AID - doi220013 [pii] AID - 10.1001/jamadermatol.2022.0655 [doi] PST - ppublish SO - JAMA Dermatol. 2022 May 1;158(5):533-541. doi: 10.1001/jamadermatol.2022.0655.