Infliximab and adalimumab show comparable infection risk in pediatric IBD

Infliximab and adalimumab, the only biologics approved by the FDA for pediatric inflammatory bowel disease (IBD), carry similar risks of serious and outpatient infection when compared head-to-head in real-world use, according to a propensity-matched cohort study published in JAMA Network Open.¹ Using 2 nationwide commercial claims databases, researchers found no clinically meaningful difference in infection risk between the 2 anti–tumor necrosis factor (TNF) agents across nearly a decade of pediatric prescribing data.¹

The study, led by investigators at Brigham and Women's Hospital and Boston Children's Hospital, addresses a long-standing evidence gap: despite both drugs' first-line status in pediatric Crohn disease (CD) and ulcerative colitis (UC), no head-to-head trial has directly compared their infection risk in children.¹⁻⁴

Infliximab vs adalimumab study design in pediatric IBD

Investigators used the Merative MarketScan Commercial Database (2016-2023) and Optum's Clinformatics Data Mart Database (2016-2025) to identify new biologic initiators aged 6 to 17 years with a diagnosis of CD or UC.¹ After applying exclusion criteria that removed children with recent infections, immunocompromising conditions, or overlapping indications, the cohort included 2467 children initiating infliximab and 1772 initiating adalimumab.¹ Propensity score matching on demographic, clinical, medication, and health care utilization variables yielded 1533 matched pairs with well-balanced baseline characteristics.¹ Follow-up extended up to 180 days from treatment initiation, with serious infections defined as hospitalization for a validated set of infectious diagnoses and outpatient infections defined as an infection diagnosis paired with a dispensed antimicrobial within 1 day.¹

Serious and outpatient infection rates with infliximab and adalimumab

Serious infections were rare in both groups: incidence rates were 29 per 1000 person-years with infliximab compared with 34 per 1000 person-years with adalimumab, yielding a pooled hazard ratio (HR) of 1.15 (95% CI, 0.63-2.11).¹ Outpatient infections were considerably more common, occurring at rates of 358 per 1000 person-years with infliximab and 386 per 1000 person-years with adalimumab (pooled HR, 1.08; 95% CI, 0.90-1.29).¹ No mycobacterial infections were identified in either treatment group, and skin and soft tissue infections were the most frequent serious infection subtype.¹ Six sensitivity analyses, including restriction to monotherapy, originator products only, first-line users, extended 365-day follow-up, and high-dimensional propensity score matching, produced estimates consistent with the primary findings.¹

Disease burden and treatment landscape in pediatric IBD

Pediatric IBD prevalence has been rising in the US and is now estimated at 122 cases per 100,000 children, and roughly 43% of patients with IBD receive biologic therapy before age 18.² Infliximab, approved for IBD in 1998, and adalimumab were the first FDA-approved biologics for pediatric IBD, and current international guidelines recommend both as first-line options for CD and UC despite the historical absence of comparative safety data to guide selection between them.⁴

How the findings compare with prior infliximab and adalimumab safety data

The results contrast with a Danish nationwide cohort study in adults with UC, which reported a substantially elevated, though imprecisely estimated, risk of serious infection with adalimumab relative to infliximab (HR, 5.11; 95% CI, 1.20-21.80).³ The new pediatric findings instead align with 2 larger US-based adult studies that found no meaningful difference in serious infection risk between the agents.¹ The study authors also noted that a negative control analysis of tendinitis, a condition not expected to be linked to anti-TNF choice, showed no evidence of differential health care-seeking behavior between groups that might have biased the comparison.¹

Limitations of the pediatric infliximab-adalimumab comparison

The authors cautioned that residual confounding from unmeasured factors cannot be fully excluded, and that limited event counts constrained precision for specific infection subtypes despite this being the largest cohort of its kind assembled to date.¹ The analysis was also restricted to commercially insured children, which may limit generalizability to publicly insured populations, and outcome misclassification remains possible despite the use of algorithms with reported positive predictive values as high as 80.2%.¹

References

1. Lyu N, Tracy M, Schneeweiss S, Savage TJ. Risk of infections with infliximab vs adalimumab among children with inflammatory bowel disease. JAMA Netw Open. 2026;9(7):e2622684. doi:10.1001/jamanetworkopen.2026.22684

2. Kappelman MD, Brensinger C, Parlett LE, Hurtado-Lorenzo A, Lewis JD. Prevalence of pediatric inflammatory bowel disease in the United States: pooled estimates from three administrative claims data sources. Gastroenterology. 2025;168(5):980-982. doi:10.1053/j.gastro.2024.11.004

3. Singh S, Andersen NN, Andersson M, Loftus EV Jr, Jess T. Comparison of infliximab and adalimumab in biologic-naive patients with ulcerative colitis: a nationwide Danish cohort study. Clin Gastroenterol Hepatol. 2017;15(8):1218-1225.e7. doi:10.1016/j.cgh.2016.11.024

4. van Rheenen PF, Aloi M, Assa A, et al. The medical management of paediatric Crohn's disease: an ECCO-ESPGHAN guideline update. J Crohns Colitis. 2021;15(2):171-194. doi:10.1093/ecco-jcc/jjaa161