Association Between Vedolizumab Treatment and Arthritis/Arthralgia in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Background and aims: Vedolizumab is a humanized gut selective drug that targets α4β7 integrin and has been used successfully in the treatment of inflammatory bowel disease (IBD). Pivotal studies have already demonstrated the drug's safety, but some real-life cohorts have shown an increase in arthralgia and arthritis in patients using vedolizumab. These findings raised the question of whether these joint symptoms are extraintestinal manifestations of IBD (since the drug acts only in the gut) or if they are associated with the use of vedolizumab. This systematic review and meta-analysis aimed to assess the incidence of arthralgia/arthritis in patients receiving vedolizumab and to investigate whether these events are indeed drug related.

Methods: Pubmed, Cochrane, and Scopus were searched for randomized clinical trials reporting the incidence of joint manifestations in patients with Crohn's disease (CD) or ulcerative colitis (UC) who were treated with vedolizumab. The considered outcomes were arthritis and arthralgia. We used RevMan to calculate the pooled incidence of the reported outcomes and their corresponding 95% confidence intervals (95% CI).

Results: The search strategy yielded 4,206 articles. After removal of duplicates and screening of results, 6 randomized studies met the inclusion criteria. A total of 3,134 patients with moderately to severe IBD were included. Of those, 2,119 were randomized to receive vedolizumab and 1,015 to placebo. In the intervention group, 210 patients developed arthritis or arthralgia of any kind while 84 patients developed those symptoms in the placebo group (RR=1.09; 95%CI: 0.86-1.38; p=0.49, I2=0%), showing no significant association. Results also showed no significant association between exposure and the studied outcome after comparing CD (RR=1.02; 95%CI: 0.76-1.37, p=0.89, I2=0%) and UC (RR=1.24; 95%CI: 0.81-1.89, p=0.32, I2=43%) separately.

Conclusions: The meta-analysis showed no association of these symptoms to the treatment with vedolizumab. Therefore, the new onset of worsening arthritis and arthralgia may be associated with the course of the disease itself, with the body's response to the drugs or with the exclusion of corticosteroids or anti-TNF from concomitant treatment with vedolizumab. Further studies with larger sample sizes are required, especially randomized clinical trials comparing anti-TNF, corticosteroid and immunomodulators to evaluate the incidence of joint manifestations in patients with IBD and even other rheumatological manifestations that may be associated as well.