PMID- 28903160 OWN - NLM STAT- MEDLINE DCOM- 20171117 LR - 20190120 IS - 2168-6084 (Electronic) IS - 2168-6068 (Print) IS - 2168-6068 (Linking) VI - 153 IP - 11 DP - 2017 Nov 1 TI - Safety of Systemic Agents for the Treatment of Pediatric Psoriasis. PG - 1147-1157 LID - 10.1001/jamadermatol.2017.3029 [doi] AB - IMPORTANCE: Use of systemic therapies for moderate to severe psoriasis in children is increasing, but comparative data on their use and toxicities are limited. OBJECTIVE: To assess patterns of use and relative risks of systemic agents for moderate to severe psoriasis in children. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was conducted at 20 centers in North America and Europe, and included all consecutive children with moderate to severe psoriasis who used systemic medications or phototherapy for at least 3 months from December 1, 1990, to September 16, 2014. MAIN OUTCOMES AND MEASURES: The minimal core data set included age, sex, severity of psoriasis, systemic interventions, monitoring, adverse events (AEs), and reason for discontinuation. RESULTS: For 390 children (203 girls and 187 boys; mean [SD] age at diagnosis, 8.4 [3.7] years) with psoriasis who used 1 or more systemic medications, the mean interval between diagnosis and starting systemic therapy was 3.0 years. Methotrexate was used by 270 patients (69.2%), biologic agents (primarily etanercept) by 106 (27.2%), acitretin by 57 (14.6%), cyclosporine by 30 (7.7%), fumaric acid esters by 19 (4.9%), and more than 1 medication was used by 73 (18.7%). Of 270 children taking methotrexate, 130 (48.1%) reported 1 or more AEs associated with methotrexate, primarily gastrointestinal (67 [24.8%]). Folic acid 6 days per week (odds ratio, 0.16; 95% CI, 0.06-0.41; P < .001) or 7 days per week (OR, 0.21; 95% CI, 0.08-0.58; P = .003) protected against gastrointestinal AEs more than once-weekly folic acid, regardless of the total weekly dosage. Methotrexate-associated hepatic transaminase elevations were associated with obesity (35 of 270 patients [13.0%]), but a folic acid regimen was not. Injection site reactions occurred in 20 of 106 patients (18.9%) treated with tumor necrosis factor inhibitors, but did not lead to discontinuation of treatment. Having 1 or more AEs related to medication, gastrointestinal AE, laboratory abnormality, or AE leading to discontinuation of the drug was more likely with methotrexate than tumor necrosis factor inhibitors, but having 1 or more infections related to medication (predominantly upper airway) was less likely. Six patients developed a serious treatment-related AE (methotrexate, 3; fumaric acid esters, 2; and adalimumab, 1), but methotrexate and biologic agents were taken for a mean duration that was 2-fold greater than the mean duration for cyclosporine or fumaric acid esters. No patient developed tuberculosis or a malignant neoplasm. CONCLUSIONS AND RELEVANCE: Medication-related AEs occur less often with tumor necrosis factor inhibitors than with methotrexate. Folic acid administration 6 or 7 times per week protected more against methotrexate-induced gastrointestinal AEs than did weekly administration. A prospective registry is needed to track the long-term risks of systemic agents for pediatric psoriasis. FAU - Bronckers, Inge M G J AU - Bronckers IMGJ AD - Department of Dermatology, Radboud University, Nijmegen, the Netherlands. FAU - Seyger, Marieke M B AU - Seyger MMB AD - Department of Dermatology, Radboud University, Nijmegen, the Netherlands. FAU - West, Dennis P AU - West DP AD - Department of Dermatology, Northwestern University, Chicago, Illinois. AD - Department of Pediatrics, Northwestern University, Chicago, Illinois. FAU - Lara-Corrales, Irene AU - Lara-Corrales I AD - Department of Pediatric Medicine, Dermatology Section, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. FAU - Tollefson, Megha AU - Tollefson M AD - Department of Dermatology, Mayo Clinic, Rochester, Minnesota. FAU - Tom, Wynnis L AU - Tom WL AD - Department of Dermatology, Rady Children's Hospital San Diego, University of California, San Diego. AD - Department of Pediatrics, Rady Children's Hospital San Diego, University of California, San Diego. FAU - Hogeling, Marcia AU - Hogeling M AD - Department of Dermatology, Phoenix Children's Hospital, Phoenix, Arizona. AD - now with the Department of Dermatology, University of California, Los Angeles. FAU - Belazarian, Leah AU - Belazarian L AD - Department of Dermatology, University of Massachusetts Medical School, Worcester. FAU - Zachariae, Claus AU - Zachariae C AD - Department of Dermatology and Allergy, Herlev-Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. FAU - Mahe, Emmanuel AU - Mahe E AD - Department of Dermatology, Hopital Victor Dupouy Argenteuil, Argenteuil, France. FAU - Siegfried, Elaine AU - Siegfried E AD - Department of Dermatology, St Louis University School of Medicine, St Louis, Missouri. AD - Department of Pediatrics, St Louis University School of Medicine, St Louis, Missouri. FAU - Philipp, Sandra AU - Philipp S AD - Psoriasis Research and Treatment Center, Charite-Universitats-Medizin, Berlin, Germany. FAU - Szalai, Zsuzsanna AU - Szalai Z AD - Department of Dermatology, Heim Pal Children's Hospital, Budapest, Hungary. FAU - Vleugels, Ruth Ann AU - Vleugels RA AD - Department of Dermatology, Boston Children's Hospital, Boston, Massachusetts. FAU - Holland, Kristen AU - Holland K AD - Department of Dermatology, Medical College of Wisconsin, Milwaukee. AD - Department of Pediatrics, Medical College of Wisconsin, Milwaukee. FAU - Murphy, Ruth AU - Murphy R AD - Paediatric Dermatology Department, Nottingham University Hospitals, Nottingham, England. FAU - Baselga, Eulalia AU - Baselga E AD - Department of Dermatology, Hospital de la Sanat Creu i Sant Pau, Barcelona, Spain. FAU - Cordoro, Kelly AU - Cordoro K AD - Department of Dermatology, University of California, San Francisco Medical Center, San Francisco. AD - Department of Pediatrics, University of California, San Francisco Medical Center, San Francisco. FAU - Lambert, Jo AU - Lambert J AD - Department of Dermatology, Ghent University Hospital, Ghent, Belgium. FAU - Alexopoulos, Alex AU - Alexopoulos A AD - First Department of Pediatrics, Agia Sofia Children's Hospital, University of Athens Medical School, Athens, Greece. FAU - Mrowietz, Ulrich AU - Mrowietz U AD - Psoriasis Center at the Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany. FAU - Kievit, Wietske AU - Kievit W AD - Department for Health Evidence, Radboud University, Nijmegen, the Netherlands. FAU - Paller, Amy S AU - Paller AS AD - Department of Dermatology, Northwestern University, Chicago, Illinois. AD - Department of Pediatrics, Northwestern University, Chicago, Illinois. CN - Psoriasis Investigator Group (PsIG) of the Pediatric Dermatology Research Alliance and the European Working Group on Pediatric Psoriasis (EWGPP) LA - eng GR - K23 AR060274/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - JAMA Dermatol JT - JAMA dermatology JID - 101589530 RN - 0 (Dermatologic Agents) RN - 0 (Immunosuppressive Agents) RN - 0 (Tumor Necrosis Factor-alpha) RN - 935E97BOY8 (Folic Acid) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Adolescent MH - Child MH - Child, Preschool MH - Dermatologic Agents/administration & dosage/adverse effects/*therapeutic use MH - Europe MH - Female MH - Folic Acid/administration & dosage MH - Humans MH - Immunosuppressive Agents/administration & dosage/adverse effects/*therapeutic use MH - Male MH - Methotrexate/administration & dosage/adverse effects/therapeutic use MH - North America MH - Psoriasis/*drug therapy/pathology MH - Retrospective Studies MH - Severity of Illness Index MH - Treatment Outcome MH - Tumor Necrosis Factor-alpha/*antagonists & inhibitors PMC - PMC5710436 COIS- Conflict of Interest Disclosures: Dr Cordoro reported serving as a consultant for and receiving honoraria from Celgene and Pfizer. Dr Holland reported serving as a consultant for and receiving honoraria from Amgen, and serving as a consultant for and receiving honoraria from Pfizer. Dr Lara-Corrales reported serving as a consultant and investigator for and receiving honoraria from AbbVie, Janssen, and Eli Lilly. Dr Mahe reported serving as a consultant for and receiving honoraria from AbbVie, Janssen-Cilag, Novartis, and Pfizer, and serving as an investigator for AbbVie, Amgen, AstraZeneca, Boehringer, Novartis, and Pfizer. Dr Mrowietz reported serving as a consultant and investigator for and receiving honoraria from AbbVie, Almirall Hermal GmbH, Amgen, Boehringer-Ingelheim, Celgene, Janssen, Eli Lilly, Merck, Novartis, and Pfizer. Dr Paller reported serving as a consultant for and receiving honoraria from AbbVie, and serving as a consultant and investigator for Amgen, Eli Lilly, Janssen, Novartis, and Pfizer. Dr Philipp reported receiving travel grants or honoraria or serving as a consultant member of the advisory board and speaker's bureau for AbbVie Deutschland GmbH & Co. KG, Almirall Hermal GmbH, Amgen GmbH, Biogen IDEC GmbH, BMS GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, Celgene GmbH, Charite Research Organisation GmbH, Janssen-Cilag GmbH, Leo Pharma GmbH, Lilly Deutschland GmbH, MSD Sharp & Dohme GmbH, Novartis Pharma GmbH, and Pfizer Deutschland GmbH. Dr Seyger reported serving as a consultant for and receiving honoraria from AbbVie, Almirall, Boehringer Ingelheim, Lilly, and Pfizer; serving as a speaker for AbbVie, Lilly, and Pfizer; traveling to meetings with AbbVie, Lilly, Pfizer, and Leo Pharma; and serving as an investigator (with funds paid directly to the institution) for AbbVie, Almirall, Astellas, Leo Pharma, and Pfizer. Dr Siegfried reported serving as a consultant for and receiving honoraria from Boehringer-Ingelheim, Eli Lilly, and Novartis, and serving as an investigator for Amgen, Eli Lilly, and Janssen. Dr Tom reported serving as an investigator for Amgen, Celgene, and Janssen. Dr Zachariae reported serving as a consultant for and receiving honoraria from AbbVie, Janssen-Cilag, Eli Lilly, Merck, and Novartis, and serving as an investigator for Amgen and AbbVie. Dr Cordoro reported serving as a consultant for and receiving honoraria from Valeant. Dr Lara-Corrales reported serving as a consultant for Johnson & Johnson, Valeant, and Pierre-Fabre, and serving as an investigator for Galderma. Dr Mahe reported serving as an investigator for Leo Pharma. Dr Mrowietz reported serving as an advisor for, receiving speakers honoraria from, receiving grants from, and/or participating in clinical trials with Biogen, Celgene, Centocor, Dr Reddy's, Foamix, Forward Pharma, Leo Pharma, Medac, Miltenyi Biotech, UCB, VBL, and Xenoport. Dr Paller reported serving as a consultant and investigator for and receiving honoraria from Amicus, Celgene, and Leo, and serving as a consultant and receiving honoraria from Dermira, Galderma, Genentech, GSK, Krystal Biotech, Pierre-Fabre, Puricore, Procter & Gamble, Roivant, Sanofi-Regeneron, and Valeant. Dr Philipp reported serving as a consultant member of advisory boards and speaker's bureaus for Biogen IDEC GmbH, BMS GmbH, Celgene GmbH, Charite Research Organisation GmbH, Dermira Inc, Forward Pharma, GlaxoSmithKline GmbH & Co KG, Leo Pharma GmbH, Maruho Europe Ltd, MSD Sharp & Dohme GmbH, Mundipharma, VBL Therapeutics, and UCB Pharma. Dr Siegfried reported serving as a consultant for and receiving honoraria from Boehringer-Ingelheim, Novartis, Pierre Fabre, Verrica, Regeneron, Sanofi, Stiefel, Glaxo, and Pfizer. Dr Zachariae reported serving as a consultant for and receiving honoraria from Takeda, and serving as an investigator for Leo Pharma, Regeneron, MSD, and Takeda. No other conflicts were reported. EDAT- 2017/09/14 06:00 MHDA- 2017/11/29 06:00 PMCR- 2018/11/08 CRDT- 2017/09/14 06:00 PHST- 2017/09/14 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2017/09/14 06:00 [entrez] PHST- 2018/11/08 00:00 [pmc-release] AID - 2652682 [pii] AID - doi170040 [pii] AID - 10.1001/jamadermatol.2017.3029 [doi] PST - ppublish SO - JAMA Dermatol. 2017 Nov 1;153(11):1147-1157. doi: 10.1001/jamadermatol.2017.3029.