Safety of Systemic Agents for the Treatment of Pediatric Psoriasis

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 PARTICIPANTSA 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 MEASURESThe 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.

Clinical use of dimethyl fumarate in moderate‐to‐severe plaque‐type psoriasis: a European expert consensus

“…Although the use of DMF in the paediatric population is off-label, there are numerous case reports, case series and unpublished clinical experience to suggest that FAEs may be an effective treatment option for children and adolescents if a systemic therapy is indicated. [31][32][33][34][35] A German multicentre, retrospective study on the efficacy and safety of long-term use of FAEs in children and adolescents showed that FAEs were often used successfully in clinical practice as off-label therapy. 36 Trials of DMF in paediatric populations and for more moderate disease are ideally needed.…”

Biological treatments for paediatric psoriasis : a retrospective observational study on biological drug survival in daily practice in childhood psoriasis

“…Moderate-to-severe cases of psoriasis may either require general treatments, such as phototherapy, or require conventional systemic treatments such as acitretin, ciclosporin, methotrexate or fumaric acid esters. 5,6 However, data are sparse on the efficacy and toxicity of systemic agents in the paediatric population. [6][7][8] Standardised guidelines are lacking, and few clinical trials have been conducted in children.…”

“…5,6 However, data are sparse on the efficacy and toxicity of systemic agents in the paediatric population. [6][7][8] Standardised guidelines are lacking, and few clinical trials have been conducted in children. 5,[9][10][11] Targeted therapies, including tumour necrosis factor alpha blockers (anti-TNFa agents) and ustekinumab, have recently been shown to be effective and safe as therapies for childhood psoriasis in controlled trials.…”

Sustained long‐term efficacy and safety of adalimumab in paediatric patients with severe chronic plaque psoriasis from a randomized, double‐blind, phase III study

“…23 Biologic treatment of psoriasis in children is reported as less likely to result in adverse events or in treatment discontinuation compared with MTX. 24 The current analysis reports results from the first randomized 52-week controlled trial, comparing the efficacy and safety of a biologic treatment, ADA (Humira â , AbbVie Inc., North Chicago, IL, U.S.A.), a recombinant fully human monoclonal antibody directed against TNF-a, with the active comparator MTX, in children with severe plaque psoriasis. Results from the first three periods of this trial have been reported.…”

“…Results of long‐term treatment of children with moderate‐to‐severe psoriasis have been published for open‐label etanercept, and for ustekinumab vs. placebo . Biologic treatment of psoriasis in children is reported as less likely to result in adverse events or in treatment discontinuation compared with MTX …”