Advanced combination therapies for refractory IBD show low serious adverse event rates in meta-analysis
Background
Inflammatory Bowel Disease (IBD) remains challenging, with many patients experiencing inadequate treatment response, progressive disease, and irreversible complications despite major therapeutic advances. Current management often hits a biological efficacy ceiling, necessitating exploration of new strategies. Combination therapies, leveraging different mechanisms, are being investigated to overcome this limitation and improve outcomes for patients with refractory disease, aiming for better disease control and reduced need for surgery.
Study Design
This systematic review and meta-analysis synthesized evidence on the safety and exploratory efficacy of advanced combination therapy (ACT) in adults with IBD. Researchers searched Embase, MEDLINE, and PubMed, including randomized controlled trials, observational, and descriptive studies published between 2015 and 2026. Fifty-two studies, totaling n=2022 participants, were included. Data extraction and risk of bias assessment used Joanna Briggs Institute tools and Cochrane RoB-1. Pooled proportions of total adverse events (TAEs), serious adverse events (SAEs), and treatment discontinuations were calculated using random-effects meta-analysis, with subgroup analyses by drug class.
Results
The meta-analysis of 52 studies (n=2022) identified anti-TNFa plus integrin inhibitors and IL-23 plus integrin inhibitors as the most frequent combination therapies. Pooled analyses demonstrated generally low rates of serious adverse events (SAEs) and treatment discontinuations for ACT in selected patients with refractory IBD. For instance, combinations of anti-TNFa plus integrin inhibitors showed SAE rates of 2.7% (95% CI 0.22% to 6.86%). Overall pooled discontinuations were 6.38% (95% CI 2.36% to 11.58%). However, the certainty of evidence was very low, and substantial heterogeneity was observed across studies, with some analyses based on small sample sizes. Efficacy outcomes were explored but not detailed in the abstract. > Advanced combination therapies for refractory IBD were associated with low rates of serious adverse events, with anti-TNFa plus integrin inhibitors showing SAEs at just 2.7% (95% CI 0.22% to 6.86%).
Key Findings
- Advanced combination therapies (ACT) for refractory IBD showed low rates of serious adverse events (SAEs).
- Anti-TNFa plus integrin inhibitor combinations had SAE rates of 2.7% (95% CI 0.22% to 6.86%).
- Overall treatment discontinuations for ACT were 6.38% (95% CI 2.36% to 11.58%).
- The most frequent combinations involved
anti-TNFaplus integrin inhibitors orIL-23plus integrin inhibitors. - Evidence certainty was very low due to small sample sizes, heterogeneity, and observational designs.
Why It Matters
This meta-analysis provides initial, albeit limited, reassurance regarding the safety profile of advanced combination therapies for patients with refractory IBD. Clinicians may consider ACT as a viable option for difficult-to-treat IBD, knowing that serious adverse event rates appear low. While the evidence certainty is low, these findings support further investigation into ACT, potentially paving the way for more effective treatment protocols for patients who have exhausted standard options. This suggests a potential shift towards more aggressive, multi-modal approaches in managing severe IBD, moving beyond the current efficacy ceiling of monotherapy.
inflammatory-bowel-disease
ibd
combination-therapy
anti-tnf
integrin-inhibitor
il-23-inhibitor