Is Vedolizumab the Answer to Decreasing the Incidence of Immune-Mediated Colitis in Patients with Pre-existing Inflammatory Bowel Disease?

Majdoline Jayoushe MD, Nancy Gupta MD, Emanuelle Bellaguarda MD Division of Gastroenterology and Hepatology Northwestern University Feinberg School of Medicine, Chicago, IL

CASE DESCRIPTION Key Points: DISCUSSION  For IBD patients anticipating immunotherapy, IBD A 63-year-old woman with past medical history of left-sided ulcerative therapy should not be discontinued, despite clinical and colitis (UC) diagnosed at the age of 23 was in clinical and endoscopic There have been a few reports documenting clinical outcomes of endoscopic remission. remission on 250 mg azathioprine (AZA) and sulfasalazine 4 g daily. AZA Vedolizumab therapy in patients with IMC. To our knowledge, there is  An integrated management plan between oncologists was discontinued after her diagnosis of metastatic melanoma, and she was no published data on the specific management of pre-existing IBD in and gastroenterologists is required in order to manage started on immunotherapy with Ipilimumab and Nivolumab. After 4 cycles patients starting immunotherapy. Our case is unique in that the patient this special population of patients. of treatment she presented with symptoms of diffuse abdominal cramping, had achieved clinical remission of her UC while on AZA, but required bleeding per rectum, and increased bowel frequency. Initial work up  Switching from 5-ASAs and immunomodulators to anti- discontinuation of therapy after diagnosis of cancer. It is important to revealed CRP 2.5 mg/dL (N: <0.5 mg/dL), and stool studies that were raise awareness among clinicians on the aftermath of discontinuing IBD integrins like Vedolizumab might be a safer option both negative for any bacterial infection, including Clostridium difficile, or therapy for patients who are anticipating immunotherapy. prior to and during immunotherapy. parasitic infection. Colonoscopy demonstrated moderate inflammation, Mayo Clinic Endoscopic Score 2 (MCS), extending continuously from the This special population requires a multidisciplinary approach and an rectum proximally to 35cm from the anal verge, with gradual transition to integrated management plan in order to avoid potentially life- normal healthy mucosa in the proximal colon. threatening immune-related adverse events and a flare from underlying Pathology showed cryptitis and crypt abscesses with focal ulceration in the IBD. Switching to therapies with a better safety profile and no systemic recto-sigmoid colon. Initial trial of oral prednisone failed to achieve immunosuppression, like anti-integrins, might be a possible option both induction. Her immunotherapy was held and she was started on prior to and during immunotherapy. Whether this will decrease the INTRODUCTION Vedolizumab therapy. She was successfully tapered off of steroids and incidence of future IMC in this population is yet to be supported with achieved clinical and endoscopic remission after 7 months of maintenance future research. therapy with Vedolizumab. Follow-up colonoscopy demonstrated mildly Immune checkpoints are immunosuppressive proteins expressed by active pan-ulcerative colitis (MCS 1). Subsequently, she was able to resume activated T-lymphocytes which evade the attack of the endogenous treatment with Nivolumab monotherapy without any issues. Ipilimumab REFERENCES immune system on tumor cells. The role of immune checkpoint inhibitors was not resumed after the IMC episode, and the patient continues on

(ICIs) in modern cancer treatment has gained more widespread Vedolizumab every 4 weeks as her maintenance therapy for UC. 1. Abu-Sbeih, H., Ali, F. S., Alsaadi, D., Jennings, J., Luo, W., Gong, Z., … Wang, Y. (2018). Outcomes of attention in the last ten years with their favorable outcomes on survival Vedolizumab Treatment in Patients With Immune Checkpoint Inhibitor-Induced Diarrhea and Colitis: A Multi- Center Study. American Journal of Gastroenterology, 113(Supplement), S58. doi:10.14309/00000434- rates. Immune mediated gastrointestinal side effects, including diarrhea 201810001-00110 and colitis, were reported in approximately 30% of patients receiving 2. Abu-Sbeih, H., Ali, F. S., Wang, X., Mallepally, N., Chen, E., Altan, M., … Wang, Y. (2019). Early introduction of therapy with ICIs. Current practice guidelines recommend corticosteroid selective immunosuppressive therapy associated with favorable clinical outcomes in patients with immune checkpoint inhibitor–induced colitis. Journal for ImmunoTherapy of Cancer, 7(1). doi:10.1186/s40425-019-0577- therapy as first-line management of immune-mediated colitis (IMC), and 1 immunosuppressive therapy, such as with Infliximab or Vedolizumab, for 3. Bertha, M., Bellaguara, E., Kuzel, T., & Hanauer, S. (2017). Checkpoint Inhibitor-Induced Colitis: A New Type of steroid-refractory IMC. Yet, there is very little awareness in the literature Inflammatory Bowel Disease? ACG Case Reports Journal, 4(1), e112. doi:10.14309/crj.2017.112 on tailoring the management of pre-existing inflammatory bowel disease 4. Som, A., Mandaliya, R., Alsaadi, D., Farshidpour, M., Charabaty, A., Malhotra, N., & Mattar, M. C. (2019). Immune checkpoint inhibitor-induced colitis: A comprehensive review. World Journal of Clinical Cases, 7(4), 405-418. (IBD) in patients who experience IMC due to ICI therapy. doi:10.12998/wjcc.v7.i4.405

5. Yamauchi, R., Araki, T., Mitsuyama, K., Tokito, T., Ishii, H., Yoshioka, S., … Torimura, T. (2018). The characteristics of nivolumab-induced colitis: an evaluation of three cases and a literature review. BMC Gastroenterology, 18(1). doi:10.1186/s12876-018-0864-1

Fig.1 Colonoscopic findings of moderate inflammation (MCS 2) extending continuously from rectum to 35 cm from anal verge before treatment with Vedolizumab.