Dual Targeted Therapy for Refractory Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Emerging evidence suggests that dual targeted therapy (DTT), which employs two biologics or small molecules concurrently, may improve outcomes for patients with refractory inflammatory bowel disease (IBD). We conducted a systematic review and meta-analysis to assess the efficacy and safety of DTT, with a comparative evaluation of different combination therapies.

We systematically searched MEDLINE, Embase, Cochrane Library, CBM, CNKI, VIP, and WanFang from inception to March 8, 2026. Eligible studies were clinical trials or cohort studies reporting DTT outcomes in IBD. Efficacy outcomes included clinical response, clinical remission, clinical improvement, and endoscopic improvement; safety outcomes included adverse events (AEs) and serious adverse events (SAEs).

Sixty-three studies comprising 2097 patients were included. Overall, DTT exhibited promising efficacy in refractory IBD, with pooled clinical response and remission rates of 68.0% (95% confidence interval [CI], 62.7%-72.8%) and 50.7% (95% CI, 44.2%-57.1%), respectively. Antitumor necrosis factor α (TNFα) plus IL-12/23 inhibitors was associated with higher clinical improvement than anti-TNFα plus anti-integrin therapy (odds ratio [OR] = 4.74; 95% CI, 2.31-9.73) and anti-integrin plus Janus kinase inhibitors (OR = 17.52; 95% CI, 1.09-281.12) in IBD patients. The safety profile of DTT was acceptable, with pooled rates of AEs and SAEs being 28.2% (95% CI, 21.9%-35.5%) and 8.3% (95% CI, 6.3%-10.8%), respectively. Notably, anti-integrin plus IL-12/23 inhibitors showed lower AE rates than anti-TNFα plus IL-12/23 inhibitors (OR = 0.19; 95% CI, 0.06-0.65).

DTT shows promising efficacy with an acceptable safety profile in refractory IBD. Large-scale, high-quality studies are required to validate these findings.