Background Treatment with biotechnological agents (infliximab, etanercept, adalimumab, golimumab and certolizumab pegol) in ankylosing spondylitis (AS) is effective. However, evidence regarding the potential efficacy of these anti-TNF drugs in the extra-articular manifestations of ankylosing spondylitis, namely in uveitis (UV), inflammatory bowel disease (IBD) and dactylitis is scarce.

Objectives To analyze evidence on efficacy of anti-TNF drugs approved for AS treatment in UV, IBD and dactylitis associated with AS.

Methods A systematic literature review was performed using the PubMed and Cochrane Library databases. Randomized controlled trials (RCT), meta-analyzes and observational studies (OS) reporting efficacy of anti-TNF agents in extra-articular manifestations of AS were included.

Results Fifty studies were included (seventeen RCTs, six meta-analyses and twenty seven observational studies). From the RCT we extracted the results presented in Table 1 for uveitis and in Table 2 for IBD. None reported results for dactylitis. Of the meta-analyzes included, only one presents results. These one shows that the incidence of uveitis is lower in patients taking etanercept than placebo (incidence of 8.6 and 19.3 per 100 patients per year, respectively; p value =0.03). In OS comparing different drugs, in one the risk of developing uveitis was 1.9 times higher in patients under etanercept compared to those under adalimumab (p value =0.0223) and a risk similar to those under infliximab and those under adalimumab. In another we have a percentage of patients with uveitis, during the course of the study, under etanercept of 8.0% and under infliximab of 4.0%. In the OS, the percentage of patients with UV events with infliximab was in a range of 0.0%>3.1% with a follow-up interval between 2 years and 5 years; with etanercept was 0.9%>29.6% and a follow-up time interval between 12 weeks to 7 years; with adalimumab there is only one study with duration of 2 years reporting 3.9% UV events. Regarding IBD reported in OS, there was 3.7%>7.7% patients with events under treatment with etanercept over a follow-up time of 3.2–7 years; with adalimumab only a 2-year study reported IBD in 0.6% of cases. We did not find results regarding for other extra-articular manifestations or anti-TNF drugs.

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Conclusions Efficacy of anti-TNF drugs on extra-articular manifestations of AS is under-reported in RCTs. Available data suggests possible efficacy of infliximab, adalimumab and certolizumab in UV, and of certolizumab in IBD. No evidence is available about anti-TNF efficacy in AS-associated dactylitis. Future studies with anti-TNF drugs should better report on extra-articular manifestations in AS.

Disclosure of Interest None declared