LAUSR

To the Editors: Despite the introduction of new biological therapies, many patients with inflammatory bowel disease remain refractory to available treatments.1 Thus, assessing whether specific biological agents can be safely used in combination is a timely question. Here, we report the case of a 22-yearold woman who presented to us with refractory Crohn’s disease. This patient was diagnosed at age 11 and suffered from a complicated course that included severe colonic involvement with multiple strictures, eventually requiring subtotal colectomy and end ileostomy. Moreover, she also developed aggressive penetrating disease with enterocutaneous perianal fistulas. Over the course of her disease, she received infliximab, adalimumab, certolizumab, natalizumab, and vedolizumab combined with immunomodulators with poor responses, and in some instances, poorly tolerated side effects including infections. At the time she presented to us, ustekinumab2 had been initiated because of progressive and unresponsive disease affecting her small bowel and rectal stump with development of perianal fistulas (Fig. 1) and severe vulvar disease. However, despite this intervention, there was little subjective change in her gastrointestinal complaints and her vulvo-perianal disease continued to progress. A dermatologic evaluation demonstrated moderate to severe vulvo-perianal disease characterized by ulcerations with fibrinoid base involving the labia majora and perineum, which was treated with topical and oral metronidazole.3 Because of the unresponsive nature of the disease, vedolizumab,4,5 which had been ineffective as monotherapy in this patient, was added to the ustekinumab and methotrexate regimen. At her 8-week follow-up, the vulvo-perianal disease had improved dramatically. She subsequently underwent completion proctectomy with perineal reconstruction. This patient has now been on combination therapy with vedolizumab, ustekinumab, and methotrexate for over 1 year and has achieved deep remission for the first time in 10 years, without any evidence of active disease in the small bowel, based on ileoscopy, magnetic resonance enterography and stool calprotectin. Her vulvo-perianal disease has improved dramatically, and there is no evidence of any penetrating complications. Furthermore, other than an episode of self-limited rotavirus infection, she has not had any infectious complications related to her therapy. This case suggests that the addition of vedolizumab to the existing biological therapy may improve or stabilize refractory disease. Moreover, given its mechanism of action, it seems reasonable to postulate that integrin blockade could be safely combined with other biological agents, without substantially increasing the risk of infection, a notion that should be tested in clinical trials.