(R) Risk of Infection in Children with Psoriasis Receiving Treatment with Ustekinumab, Etanercept, or Methotrexate

Publication Number: 1017

Background: Pediatric psoriasis is a chronic inflammatory skin disease associated with significant impact on quality of life. Children with psoriasis are increasingly treated with systemic immunomodulatory medications, yet their risk of infection, including serious, is not well characterized in clinical practice.

Objectives: In head-to-head comparisons, we sought to estimate the 6-month rate of outpatient infections and serious infections in children with PsO treated with systemic immunomodulary agents, including ustekinumab, etanercept, or methotrexate.

Methods: Using 2 national U.S. insurance claims databases, we identified a cohort of children < 18 years with PsO and compared the frequency of infection—serious infections requiring emergency department care or hospitalization, and outpatient infections requiring treatment—in those initiating ustekinumab, etanercept, or methotrexate. Cohort entry was the new use of any of the three drugs, defined as no use of the exposure or referent agent in each of 3 pair-wise comparison during the 180 days before treatment initiation. Follow-up started the day after cohort entry and lasted for 180 days. Event rates and rate ratios (RR) were estimated separately for each head-to-head comparison, after propensity-score (PS) decile stratification with trimming. Analyses were implemented separately in each database and findings were pooled with fixed-effects meta-analyses.

Results: The pooled PS adjusted rate of serious infection was 19.1 per 1,000 person-years (2 events, 6-month risk= 0.8%) in 252 ustekinumab initiators; 22.2 (3 events, 1%) in 315 etanercept initiators; 5.7 (1 event, 0.3%) in 402 methotrexate initiators. The rate of outpatient infection was 292.9 per 1,000 person-years (29 events, 11.2%) in ustekinumab; 414.6 (51 events, 16.2%) in etanercept; 406.3 (65 events, 16.17%) in methotrexate. The adjusted rate ratio of outpatient infections comparing ustekinumab vs. etanercept was RR=0.71 (0.45-1.11); ustekinumab vs. methotrexate was RR=0.73 (0.48-1.13); etanercept vs. methotrexate was RR=0.90 (0.59-1.36).

Conclusions: Among children with psoriasis who started treatment with targeted immunomodulating agents, serious infections were infrequent in clinical practice. While there was a numeric trend toward lower risk of infection in ustekinumab users, we found no meaningful difference in infection risk—serious or outpatient encounters—between ustekinumab, etanercept, methotrexate.