The impact of ustekinumab and tumor necrosis factor antagonists on extraintestinal manifestations of Crohn's disease: a systematic review and meta-analysis
In brief
Ustekinumab halves fatigue and arthritis risk in Crohn's patients
A meta-analysis of 23 trials (7,810 adults) found that ustekinumab reduced fatigue by roughly 50% and cut arthritis or arthralgia risk by about the same amount during maintenance therapy. By contrast, weekly adalimumab increased fatigue and neither adalimumab nor infliximab improved most other extraintestinal manifestations, leaving the best choice for many symptoms uncertain.
- Journal
- Frontiers in pharmacology (Q1)
- Published
- 30 July 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Mao-Xuan Lin, Ye-Xin Chen, Tu-Nan Ding, Wei Han, Mo-Han Sun, Yi-Yu Dong, et al.
- PMID
- 42597387
- DOI
- 10.3389/fphar.2026.1849397
Why clinicians should know about it
- Picked for Gastroenterology (top studies of the week, 16 August 2026): Ustekinumab vs TNF antagonists for extraintestinal CD manifestations
- Picked for Rheumatology (top studies of the week, 16 August 2026): High-quality evidence in a top journal
Abstract
OBJECTIVE: Extraintestinal manifestations (EIMs) are commonly observed in patients with Crohn's disease (CD). Although Tumor Necrosis Factor (TNF) antagonists are commonly recommended for the management of several EIMs, their efficacy remains limited. Ustekinumab (UST), an alternative option after TNF antagonists failure, has shown potential efficacy for various EIMs. However, evidence regarding its effectiveness remains inconsistent. This study aimed to evaluate the efficacy and safety of UST and TNF antagonists for CD-related EIMs through a systematic review and meta-analysis. METHODS: PubMed, Embase, and Cochrane Library were searched on 2 August 2025, to identify phase II and III randomized controlled trials (RCTs) evaluating UST or TNF antagonists in adults aged ≥18 years with moderate-to-severe active CD. The primary outcomes were EIMs and EIM-related symptoms. Two investigators, adhering to the PRISMA guidelines, independently screened the literature and extracted data. The risk of bias was assessed using the Cochrane Risk-of-Bias Tool 2.0. Random-effects and fixed-effect models were used to estimate pooled treatment effects. Results were presented using risk ratios (RRs), incidence rate ratios (IRRs) and 95% confidence intervals (CIs). RESULTS: A total of 23 RCTs, involving 7,810 patients, were included, with EIMs such as fatigue, joint pain, and skin manifestations being considered. The meta-analysis revealed that UST significantly reduced the risk of fatigue in CD patients (IRR 0.53, 95% CI 0.33-0.84, P = 0.008). During maintenance therapy, UST treatment was significantly associated with a reduction in the risk of arthritis/arthralgia (IRR 0.56, 95% CI 0.36-0.86, P = 0.008). Weekly adalimumab (ADA) treatment was significantly associated with an increased risk of fatigue (IRR 2.79, 95% CI 1.12-6.94, P = 0.028). CONCLUSION: UST showed potential advantages in the management of fatigue and arthritis/arthralgia. ADA and infliximab (IFX) were not associated with statistically significant benefits for most analyzed EIM outcomes. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251111502, identifier CRD420251111502.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.