{"doi":"10.1002/jpn3.70251","title":"Comparative risk of serious infection among biologic therapies for inflammatory bowel disease in pediatric patients: A target trial emulation","abstract":"Patients with inflammatory bowel diseases (IBD) are more susceptible to infections due to the immune dysregulation and inflammatory nature of the disease. Biologic therapies may further increase the risk, as most are immunosuppressive agents, although the degree of suppression and its association with severe infection remain uncertain. Children with IBD are a unique population, as their developing immunity and distinct disease course differ from adults.1 In the pediatric population, currently only tumor necrosis factor-alpha inhibitors (TNFi) are Food and Drug Administration-approved, while other biologics such as ustekinumab and vedolizumab are used off-label.2, 3 Yet, their treatment outcomes have been largely extrapolated from adult studies, evaluated in small pediatric cohorts, or assessed against placebos. As biologic use expands in pediatric care, establishing their safety profiles becomes essential, especially with respect to the infection risk. To fill this knowledge gap, the present study assessed the risk of serious infection associated with biologics currently used for treating children with IBD in head-to-head comparative analyses. This retrospective study was exempt from the requirement of informed consent. The analysis used existing, de-identified data and involved no intervention or interaction with human subjects. Data were de-identified in accordance with the standards outlined in Section §164.514(a) of the Health Insurance Portability and Accountability Act Privacy Rule. A qualified expert formally verified the de-identification process, with the expert determination most recently updated in December 2020. We analyzed de-identified electronic health records from multiple U.S. healthcare organizations spanning October 1, 2015 to June 30, 2024. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines. Patients with IBD (Crohn's disease [CD] or ulcerative colitis [UC]) diagnosed before 18 years of age who had been biologic-naïve were eligible for the study. The cohorts were established based on the prescriptions: TNFi (i.e., adalimumab, certolizumab, golimumab, and infliximab); immunomodulators (i.e., azathioprine, 6-mercaptopurine, and methotrexate); ustekinumab; and vedolizumab. TNFi combination therapy (combo) was defined as the concurrent use of TNFi and immunomodulators within 3 months, while TNFi monotherapy was defined as TNFi use alone during this period. Six pairwise comparisons were conducted: (1) TNFi combo versus monotherapy; (2) ustekinumab versus TNFi monotherapy; (3) ustekinumab versus TNFi combo; (4) vedolizumab versus TNFi monotherapy; (5) vedolizumab versus TNFi combo; (6) and ustekinumab versus vedolizumab. The index date was designated as the date of the first prescription. To build the temporal relationship between the diagnosis and treatment, the diagnosis was required to be documented in the records within 1 year preceding the index date. Additional details regarding the database, data acquisition, and regulations are included in Supplemental Methods S1 and Table S2. The baseline characteristics included demographics, comorbid diseases, prior medication use, and prior surgical history for IBD. The follow-up duration was 3 years for this study. All patients were tracked from the day after index date until the following censoring events: occurrence of study outcomes, death, loss to follow-up, or the end of the study period, whichever came first. The primary outcome was serious infection (defined as those requiring hospitalization, intravenous antibiotics, advanced medical intervention, or those that are life-threatening; sepsis, opportunistic infection, central nervous system infection, lower respiratory tract infection, peritonitis, pyelonephritis, and osteomyelitis).4, 5 A 1:1 propensity score matching was conducted using the nearest-neighbor algorithm, with a caliper set at 0.1 pooled standard deviations (SDs) of the logit o","journal":"Journal of Pediatric Gastroenterology and Nutrition","year":2025,"id":548960,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9504,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":51742,"name":"Ashwin N. Ananthakrishnan","orcid":"0000-0002-9436-1821","position":1,"is_corresponding":false},{"id":1304275,"name":"Harland S. Winter","orcid":"0000-0002-3202-7772","position":2,"is_corresponding":false},{"id":859459,"name":"Kevin Sheng‐Kai","orcid":"0000-0002-9394-4144","position":3,"is_corresponding":false},{"id":1207126,"name":"Serena Yun‐Chen Tsai","orcid":"0000-0002-5778-645X","position":0,"is_corresponding":true}],"reference_count":13,"raw_metadata":null,"created_at":"2026-07-19T02:54:03.053965Z","pmid":"41292289","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}