Inflammatory bowel disease risk in patients with axial spondyloarthritis treated with biologic agents: Determined Using the BSRBR-AS and a MetaAnalysis

Objectives: To determine, amongst patients with axial spondyloarthritis (axSpA), whether the risk of inflammatory bowel disease (IBD) varies between patients treated with biologic and other therapies, and whether specifically the risk is higher in patients treated with etanercept.
Methods: The British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) was used to determine the incidence of IBD during follow-up and to calculate the Incidence Rate Difference (IRD) between biologic treatment and other treatment groups. We thereafter conducted a systematic review (involving observational studies and randomised controlled trials) to perform a meta-analysis to quantify the difference in incidence of IBD between treatment groups.
Results: In BSRBR-AS, among people with axSpA, exposure to biologic therapy was associated with an increased incidence of IBD compared to non-exposed patients (IRD 11.9 95% CI (4.3, 19.6)). This finding was replicated across observational studies but not seen in placebo controlled RCTs IRD 2.2 95% CI (-4.1, 8.5). Data from BSRBR-AS do not suggest that excess incidence of IBD is associated with exposure to etanercept compared to other anti-TNFα therapies (IRD -6.5/1,000 pys 95% CI (-21.3, 8.5)). Trials and their extensions suggest a small (and not statistically significant) absolute increased incidence associated with etanercept of between 2.1 and 5.8 per 1,000 pys compared to other anti-TNFα therapies.
Conclusions: There was an excess risk of IBD amongst persons treated with biologics in observational studies. Only evidence from trials suggested that etanercept was associated with an increased risk compared to other anti-TNFα therapies, albeit with considerable uncertainty.