World J Pediatr. 2026 Jul 1. doi: 10.1007/s12519-026-01055-0. Online ahead of print.
ABSTRACT
BACKGROUND: Multiple clinical studies have confirmed that combining biologics and/or small molecules (tofacitinib or upadacitinib) exhibits favorable efficacy and manageable safety in adult patients with inflammatory bowel disease (IBD). However, data on the application of this therapy in pediatric IBD are limited and lack systematic integration and analysis. This study aims to evaluate the safety and efficacy of combining biologics and/or small molecules for the treatment of pediatric IBD and provide high-quality evidence-based guidance for pediatric clinical treatment decision making.
METHODS: We systematically searched multiple databases from inception to January 1, 2026 and included all studies that used combination therapy with biologics and/or small molecules in pediatric IBD. We conducted a pooled analysis of clinical remission rate, endoscopic remission rate, adverse event incidence, pediatric ulcerative colitis activity index (PUCAI) scores, pediatric Crohn’s disease activity index (PCDAI) scores, and changes in laboratory parameters.
RESULTS: A total of 12 studies meeting the inclusion criteria were included in the analysis, involving 217 pediatric patients with IBD. All patients had failed treatment with at least one biologic agent or immunomodulator. The primary treatment regimens included anti-tumor necrosis factor (TNF)-α + vedolizumab (accounting for 37.2%) and anti-TNF-α + ustekinumab (accounting for 28.6%). The pooled clinical remission rate was 69% [95% confidence interval (CI) = 52%-84%], the endoscopic remission rate was 51% (95% CI = 18%-83%), and the corticosteroid-free remission rate was 66% (95% CI = 41%-88%). Significant reductions were observed in C-reactive protein, fecal calprotectin, and erythrocyte sedimentation rate, as well as in PCDAI and PUCAI scores. The pooled adverse event rate was 17% (95% CI = 6%-31%), with infection being the most common. Pooled rate of serious adverse events was 11% (95% CI = 4%-20%), with no reported cases of malignancy or fatality. The clinical remission rate for ulcerative colitis was lower than that for Crohn’s disease, and the incidence of adverse events was higher, although these differences were not statistically significant.
CONCLUSIONS: For pediatric patients with IBD that is unresponsive to monotherapy, combining biologics and/or small molecules may represent an effective and relatively safe treatment option, achieving high clinical remission rates and improvements in biological markers. However, high-quality prospective studies are needed to confirm long-term efficacy and safety.
PMID:42387245 | DOI:10.1007/s12519-026-01055-0
