New Perianal Fistulas in Patients Switched From Anti-TNFs to Vedolizumab for the Treatment of Crohnʼs Disease (CD)

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Vedolizumab is an α4β7 integrin antagonist with gut specific effects on lymphocyte and monocyte trafficking. Although effective for ulcerative colitis, its effects on extra intestinal manifestations in patients with IBD have not been well described. We present three patients with CD who developed de novo perianal fistulas after being treated with vedolizumab. A 25 year old woman with a history of ileo-colonic CD, who failed infliximab, adalimumab and ustekinumab was started on vedolizumab from May 2016. She developed a perianal fistula with abscess on September 2016 and underwent fistulotomy and seton placement. She had prior erythema nodosum and uveitis but no history of preexisting perianal fistula. A 55-year-old woman with history of CD status post total proctocolectomy and creation of J pouch with recurrent strictures and inflammation within the J pouch, failed infliximab and was started on vedolizumab in September 2014. She developed a perianal fistula with abscess in August 2015 and had fistulotomy and seton placement. Patient did not have previous perianal disease. A 42 year-old-woman with jejunal CD status post multiple small bowel resections, previously tried adalimumab, infliximab, started on vedolizumab October 2015 and reported development of de novo perianal fistula in April 2016, which required placement of seton. Patient did not have prior perianal disease. This is the first case series to report development of new perianal fistulas post vedolizumab therapy in patients with long-standing CD. Importantly, this small group of patients are distinct from those with previous fistulizing disease whose disease may have worsened when they changed from anti-TNF therapy to vedolizumab. We can hypothesize that the integrins and adhesion molecules that play a role in recruitment to perianal tissue are distinct from those involved in luminal inflammation. Another hypothesis is that perianal disease could have been masked during systemic anti-TNF treatment and once patient is treated with a gut-specific agent such as vedolizumab, extra luminal manifestations including fistulas may be unmasked. On the other hand, this small group of patients had CD for many years prior to starting anti-TNFs and had never experienced fistulas as part of the natural history of their disease. Larger cohort studies are needed to determine whether a small subset of patients switched to vedolizumab develop fistulas and the mechanism by which this may occur.