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Original Investigation
November 2017

Safety of Systemic Agents for the Treatment of Pediatric Psoriasis

Author Affiliations
  • 1Department of Dermatology, Radboud University, Nijmegen, the Netherlands
  • 2Department of Dermatology, Northwestern University, Chicago, Illinois
  • 3Department of Pediatrics, Northwestern University, Chicago, Illinois
  • 4Department of Pediatric Medicine, Dermatology Section, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  • 5Department of Dermatology, Mayo Clinic, Rochester, Minnesota
  • 6Department of Dermatology, Rady Children’s Hospital San Diego, University of California, San Diego
  • 7Department of Pediatrics, Rady Children’s Hospital San Diego, University of California, San Diego
  • 8Department of Dermatology, Phoenix Children’s Hospital, Phoenix, Arizona
  • 9now with the Department of Dermatology, University of California, Los Angeles
  • 10Department of Dermatology, University of Massachusetts Medical School, Worcester
  • 11Department of Dermatology and Allergy, Herlev-Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
  • 12Department of Dermatology, Hôpital Victor Dupouy Argenteuil, Argenteuil, France
  • 13Department of Dermatology, St Louis University School of Medicine, St Louis, Missouri
  • 14Department of Pediatrics, St Louis University School of Medicine, St Louis, Missouri
  • 15Psoriasis Research and Treatment Center, Charité-Universitäts-Medizin, Berlin, Germany
  • 16Department of Dermatology, Heim Pál Children’s Hospital, Budapest, Hungary
  • 17Department of Dermatology, Boston Children’s Hospital, Boston, Massachusetts
  • 18Department of Dermatology, Medical College of Wisconsin, Milwaukee
  • 19Department of Pediatrics, Medical College of Wisconsin, Milwaukee
  • 20Paediatric Dermatology Department, Nottingham University Hospitals, Nottingham, England
  • 21Department of Dermatology, Hospital de la Sanat Creu i Sant Pau, Barcelona, Spain
  • 22Department of Dermatology, University of California, San Francisco Medical Center, San Francisco
  • 23Department of Pediatrics, University of California, San Francisco Medical Center, San Francisco
  • 24Department of Dermatology, Ghent University Hospital, Ghent, Belgium
  • 25First Department of Pediatrics, Agia Sofia Children’s Hospital, University of Athens Medical School, Athens, Greece
  • 26Psoriasis Center at the Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
  • 27Department for Health Evidence, Radboud University, Nijmegen, the Netherlands
JAMA Dermatol. 2017;153(11):1147-1157. doi:10.1001/jamadermatol.2017.3029
Key Points

Question  What are the risks of systemic medications for pediatric psoriasis?

Findings  In this cohort study of 390 children with moderate to severe psoriasis, methotrexate and tumor necrosis factor inhibitors were most frequently used; compared with methotrexate, more medication-related adverse events overall and per patient-years of use occurred with cyclosporine, acitretin, and fumaric acid esters, and fewer occurred with use of tumor necrosis factor inhibitors. Folic acid administration 6 or 7 times weekly was associated with fewer methotrexate-induced gastrointestinal adverse effects compared with once-weekly administration.

Meaning  Overall, tumor necrosis factor inhibitors were associated with fewer adverse events than methotrexate; folic acid administration 6 or 7 times weekly may lower the risk of methotrexate-related gastrointestinal adverse events compared with weekly administration.

Abstract

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.

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