Serious Infections Rare With Immunomodulating Agents for Pediatric Psoriasis

Serious infections occurred infrequently among pediatric patients with psoriasis who started treatment with methotrexate, etanercept, or ustekinumab, according to the results of a cohort study published in JAMA Dermatology.

Investigators sought to estimate the 6-month rate of infections among children who had received treatment with a topical medication for psoriasis and then began treatment with methotrexate, etanercept, or ustekinumab. The study authors stated, “These biologic immunomodulatory agents are increasingly considered as first-line systemic agents given their efficacy in treating children with psoriasis and improving their quality of life.”

They conducted a cohort study using insurance claims data (IBM MarketScan and Optum’s Clinformatics DataMart) to identify children younger than 18 years of age who had been receiving treatment with a topical medication for psoriasis and who subsequently began treatment with methotrexate, etanercept, or ustekinumab from 2009 to 2021.  

Investigators stratified analyses by the time before pediatric labeling (2009-2015) and after etanercept was approved by the US Food and Drug Administration (FDA) for treatment of psoriasis in pediatric patients (2016-2021; methotrexate and ustekinumab are not approved by the FDA for treatment of psoriasis in pediatric patients). Patients were followed beginning the first day after treatment initiation, and follow-up lasted for 6 months.

Patients with less than 180 days of continuous enrollment, with any preexisting conditions that could increase their risk for serious infections, with prior use of other systemic immunomodulating agents, and patients who started both the reference and the exposure medications on the same day were excluded from participating in the study. Patients with comorbid rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, dermatomyositis, and/or inflammatory bowel disease were also excluded.

Patient characteristics including sex, age, race and ethnicity, calendar year of entry, history of infections, prior use of medications, and health care use along with all confounders were entered as independent variables. Propensity scores were calculated using the estimated values from the resulting logistic regression model. The investigators created pairwise comparisons for analysis (ustekinumab vs etanercept [reference drug]; ustekinumab vs methotrexate [reference drug]; and etanercept vs methotrexate [reference drug]).

Investigators included 2338 patients (57.8% girls) who initiated treatment with 1 of the aforementioned immunomodulating agents from 2009 to 2021 (methotrexate, n=1180; etanercept, n=779; ustekinumab, n=379, after trimming). They included 1769 children aged 12 to 17 years, 548 aged 6 to 11 years, and 52 children aged 5 years and younger.).

The incidence rate of serious infection, propensity score-adjusted, was 25.6 per 1000 person-years (9 events) for etanercept users, 18.4 per 1000 person-years (3 events) for ustekinumab users, and 14.9 per 1000 person-years (8 events) for methotrexate users. Outpatient infection requiring treatment 6-month risk-rate was 17.8% for etanercept, 17.7% for methotrexate, and 10.3% for ustekinumab. The investigators reported no occurrence of outpatient mycobacterial infection or bone and joint infection. The most frequently occurring outpatient infections included skin and soft tissue infections, acute otitis media, streptococcal pharyngitis, and sinusitis.

The adjusted rate of outpatient infections was 435.7 per 1000 person-years (139 events) for etanercept users, 433.6 per 1000 person-years (209 events) for methotrexate users, and 254.9 per 1000 person-years (39 events) for ustekinumab users. Adjusted rate ratios of outpatient infections were 0.95 (95% CI, 0.75-1.21) for etanercept vs methotrexate, 0.66 (95% CI, 0.48-0.91) for ustekinumab vs methotrexate, and 0.58 (95% CI, 0.41-0.83) for ustekinumab vs etanercept. During the off-label use era and after pediatric labeling for etanercept, rate ratios were similar. In the off-label era, there were significantly fewer ustekinumab users (50) vs etanercept users (443). The small number of serious infections made comparison of event rates in off-label years vs the time following approval difficult.

Significant review limitations include the design nature of a review, underpowered sample sizes and few serious infection events leading to overestimation bias, Medicaid patients not being included, involving patients younger than 6 years of age, unaccounted-for overlap of data sources, unaccounted-for residual confounding, and lack of adjustment for environmental and behavioral risk factors for serious infection.

“Among children with psoriasis who started treatment with immunomodulating agents, serious infections were infrequent,” investigators concluded. They added that outpatient infections requiring treatment were more frequent. They wrote, “There was no meaningful difference in risk of infection between systemic treatment with ustekinumab, etanercept, or methotrexate.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Dermatology Advisor