PMID- 37341961 OWN - NLM STAT- MEDLINE DCOM- 20230828 LR - 20230909 IS - 1179-1888 (Electronic) IS - 1175-0561 (Print) IS - 1175-0561 (Linking) VI - 24 IP - 5 DP - 2023 Sep TI - Secukinumab in Pediatric Patients with Plaque Psoriasis: Pooled Safety Analysis from Two Phase 3 Randomized Clinical Trials. PG - 821-835 LID - 10.1007/s40257-023-00782-8 [doi] AB - BACKGROUND: Plaque psoriasis affects ~ 1% of the pediatric population, negatively impacting quality of life. The efficacy and safety of secukinumab in pediatric patients with moderate to severe or severe chronic plaque psoriasis have been established in two pivotal phase 3 trials (open-label, NCT03668613; double-blind, NCT02471144). OBJECTIVES: The aims were to report the pooled safety of secukinumab up to 52 weeks from two studies in subgroups of pediatric patients stratified by age and bodyweight, and to present, alongside the pediatric data, the pooled safety data from four pivotal adult secukinumab trials. METHODS: The safety of secukinumab was evaluated in subgroups of pediatric patients defined by age (6 to < 12 and 12 to < 18 years) and bodyweight (< 25 kg, 25 to < 50 kg, and >/= 50 kg) in the pooled population. Patients received secukinumab low dose (LD; 75/75/150 mg), secukinumab high dose (HD; 75/150/300 mg), placebo, or etanercept (0.8 mg/kg). For safety analyses, data were pooled from the pediatric studies NCT03668613 and NCT02471144, and presented alongside the pooled data from four adult pivotal studies (NCT01365455, NCT01636687, NCT01358578, NCT01555125). RESULTS: A total of 198 pediatric patients (overall exposure: 184.6 patient-years [PY]) and 1989 adult patients (1749.5 PY) receiving secukinumab up to week 52 were included in this analysis. At week 52, the incidence of adverse events (AEs) was lower in the lower age and bodyweight subgroups. The AEs reported within these subgroups were consistent with the overall AEs reported in this analysis. Overall, exposure-adjusted incidence rates for treatment-emergent AEs were lower in the secukinumab-treated pediatric pool (198.8/100 PY) compared with the etanercept (266.3/100 PY) and adult pools (256.1/100 PY). Up to 52 weeks, the incidence rates of the AEs in the secukinumab-treated patients in the 6 to < 12 years subgroup and 12 to < 18 years subgroup were 167.7/100 PY and 214.7/100 PY, respectively. Similarly, incidence rates of the AEs in the secukinumab-treated patients in the < 25 kg, 25 kg to < 50 kg, and >/= 50 kg subgroups were 177.3/100 PY, 192.5/100 PY, and 206.8/100 PY, respectively. Nasopharyngitis was the most frequently reported AE in secukinumab-treated pediatric patients across age (< 12 years: 11.8/100 PY; >/= 12 years: 42.4/100 PY) and bodyweight (< 25 kg: 22.8/100 PY; 25 kg to < 50 kg: 19.0/100 PY; >/= 50 kg: 43.0/100 PY). Of the 198 secukinumab-treated pediatric patients, one reported nail Candida, one reported skin Candida, and two reported vulvovaginal Candida. Transient and mostly mild events of neutropenia were observed with secukinumab, none leading to study treatment discontinuation. No incidence of treatment-emergent anti-drug antibodies was reported in pediatric patients treated with secukinumab. CONCLUSIONS: Secukinumab was well tolerated in pediatric patients with moderate to severe and severe plaque psoriasis across age and bodyweight subgroups. The overall safety profile of secukinumab in pediatric patients was consistent with that of adult patients. GOV IDENTIFIER: NCT03668613 (Novartis Study Code CAIN457A2311, referred to as A2311), actual study start date: August 29, 2018; actual primary completion date: September 19, 2019; estimated study completion date: September 14, 2023. NCT02471144 (Novartis Study Code CAIN457A2310, referred to as A2310), study start date: September 29, 2015; primary completion date: December 13, 2018; estimated study completion date: March 31, 2023. CI - (c) 2023. The Author(s). FAU - Sticherling, Michael AU - Sticherling M AUID- ORCID: 0000-0001-9396-3938 AD - Hautklinik, Friedrich-Alexander-University of Erlangen-Nurnberg (FAU) Department of Dermatology, University Hospital Erlangen, Ulmenweg 18, 91054, Erlangen, Germany. michael.sticherling@uk-erlangen.de. FAU - Nikkels, Arjen F AU - Nikkels AF AD - Department of Dermatology, University Hospital Centre, CHU of Sart Tilman, University of Liege, 4000, Liege, Belgium. FAU - Hamza, Ashraf M AU - Hamza AM AD - Department of Dermatology and Andrology, Alexandria University, Alexandria, Egypt. FAU - Kwong, Pearl AU - Kwong P AD - Solutions through Advanced Research, Jacksonville, FL, USA. FAU - Szepietowski, Jacek C AU - Szepietowski JC AD - Department of Dermatology, Venereology and Allergology, Medical University, Wroclaw, Poland. FAU - El Sayed, Mahira AU - El Sayed M AD - Ain Shams University, Cairo, Egypt. FAU - Ghislain, Pierre-Dominique AU - Ghislain PD AD - Cliniques Universitaires St-Luc UCL, Brussels, Belgium. FAU - Khotko, Alkes A AU - Khotko AA AD - GBUZ Clinical Dermatology and Venereological Dispensary, Krasnodar, Russia. FAU - Patekar, Manmath AU - Patekar M AD - Novartis Pharma AG, Basel, Switzerland. FAU - Ortmann, Christine-Elke AU - Ortmann CE AD - Novartis Pharma AG, Basel, Switzerland. FAU - Forrer, Pascal AU - Forrer P AD - Novartis Pharma AG, Basel, Switzerland. FAU - Papanastasiou, Philemon AU - Papanastasiou P AD - Novartis Pharma AG, Basel, Switzerland. FAU - Keefe, Deborah AU - Keefe D AD - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. LA - eng SI - ClinicalTrials.gov/NCT03668613 SI - ClinicalTrials.gov/NCT02471144 SI - ClinicalTrials.gov/NCT01555125 SI - ClinicalTrials.gov/NCT03668613 SI - ClinicalTrials.gov/NCT02471144 SI - ClinicalTrials.gov/NCT01365455 SI - ClinicalTrials.gov/NCT01636687 SI - ClinicalTrials.gov/NCT01358578 PT - Journal Article DEP - 20230621 PL - New Zealand TA - Am J Clin Dermatol JT - American journal of clinical dermatology JID - 100895290 RN - 0 (Antibodies, Monoclonal) RN - OP401G7OJC (Etanercept) RN - DLG4EML025 (secukinumab) SB - IM MH - Adolescent MH - Child MH - Humans MH - *Antibodies, Monoclonal/adverse effects MH - Double-Blind Method MH - Etanercept/adverse effects MH - *Psoriasis/drug therapy MH - Quality of Life MH - Randomized Controlled Trials as Topic MH - Severity of Illness Index MH - Treatment Outcome MH - Clinical Trials, Phase III as Topic PMC - PMC10460311 COIS- Michael Sticherling is an investigator, speaker, consultant/advisory board member, and participated in clinical trials with the following companies: AbbVie, Amgen, BMS, Celgene, Galderma, GSK, Janssen Cilag, Leo, Lilly, MSD, Mundipharma, Novartis, Regeneron, Pfizer, Sanofi, and UCB. Arjen F. Nikkels has nothing to disclosure. Ashraf M. Hamza is a principal investigator for Novartis and speaker for Sanofi and Pfizer. Pearl Kwong is an investigator, speaker, and/or consultant for Pfizer, Eli Lilly, Regeneron Sanofi Genzyme, Ortho, Verrica, Vyne, Journey, Incyte Almirall, Novartis, Amgen/Celgene, AbbVie, Dermira, Galderma, Castle Creek Biosciences, and Arcutis. Jacek C. Szepietowski is an advisory board member of AbbVie, LEO Pharma, Novartis, Pierre-Fabre, Menlo Therapeutics, Sienna Biopharmaceuticals, and Trevi Therapeutics; principal investigator for AbbVie, Novartis, Menlo Therapeutics, Trevi Therapeutics, 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 Menarini. Mahira El Sayed is a speaker and advisory board member of AbbVie, Novartis, Janssen, Amgen, Sandoz, Sanofi, Pfizer, and Eli Lilly. Pierre-Dominique Ghislain is receiving consultancy and fees as speaker, investigator, or grants for Pfizer, MSD, AbbVie, Janssen, Serono, Leo, Novartis, UCB, Amgen, Eli Lilly, Galderma, BMS, Meda, Maruho, Flen, Menarini, Almirall, PellePharm, and Viatris. Alkes A Khotko is an investigator in sponsored clinical trials of AbbVie, Novartis, Janssen, Amgen, Sanofi, Eli Lilly, Biocad, Akrikhin, Alfasigma S.p.A., OOO Pharmapark, Argenx BV, and Bristol Myers Squibb. Manmath Patekar, Christine-Elke Ortmann, Philemon Papanastasiou, Pascal Forrer, and Deborah Keefe are employees of Novartis. EDAT- 2023/06/21 13:04 MHDA- 2023/08/28 07:16 PMCR- 2023/06/21 CRDT- 2023/06/21 11:16 PHST- 2023/04/03 00:00 [accepted] PHST- 2023/08/28 07:16 [medline] PHST- 2023/06/21 13:04 [pubmed] PHST- 2023/06/21 11:16 [entrez] PHST- 2023/06/21 00:00 [pmc-release] AID - 10.1007/s40257-023-00782-8 [pii] AID - 782 [pii] AID - 10.1007/s40257-023-00782-8 [doi] PST - ppublish SO - Am J Clin Dermatol. 2023 Sep;24(5):821-835. doi: 10.1007/s40257-023-00782-8. Epub 2023 Jun 21.