A187 ASSOCIATION OF IL-17 INHIBITOR TREATMENT WITH NEW OR WORSENING INFLAMMATORY BOWEL DISEASE: A CASE SERIES

Abstract

Abstract Background Interleukin 17 (IL-17) inhibitors, monoclonal antibodies that target IL-17A (secukinumab, ixekizumab) or the IL-17 receptor (brodalumab), are effective treatments for patients with psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). IL-17A inhibitors are rarely associated with new or worsening inflammatory bowel disease (IBD), with an estimated incidence rate of 1.1/1000 patient-exposure years in Crohn’s disease (CD) and 1.0/1000 patient-exposure years in ulcerative colitis. Aims Describe 3 patients treated with IL-17 inhibitors who developed IBD. Methods Case series. Results Case 1: 50 year-old male with PsO developed bloody diarrhea after 2 months of ixekizumab therapy. Colonoscopy showed proctitis with a cobblestone appearance and anal ulceration. He failed topical 5-ASA and repeat colonoscopy 1 month later showed chronic inflammatory changes in the transverse colon and rectum. Patient was hospitalized for a right colonic perforation requiring hemicolectomy and loop ileostomy. Pathology showed mucosal ulcerations with acute transmural inflammation of the cecum, ascending colon, and ileum, with crypt architectural distortion and no granulomas. Colonoscopy 6 months later showed chronic mild patchy active colitis with granulomas. Infliximab and methotrexate were started with clinical remission of his CD and partial response of his PsO. Case 2: 39 year-old male with AS who failed golimumab and etanercept started on secukinumab, and reported acute worsening of diarrhea and abdominal pain. Colonoscopy after a year of persistent symptoms showed ulceration of the ileum and ileocecal valve. Biopsies showed mild active chronic ileitis, and architectural distortion with reactive lymphoid follicles in the right colon. He was treated with adalimumab with partial clinical response of his CD and AS. Case 3: 63 year-old female with PsA reported a 3 week history of diarrhea, abdominal pain, and fever. She was maintained on ixekizumab for 4 months and previously failed adalimumab, secukinumab, and etanercept. CT showed diffuse circumferential pancolonic wall thickening and terminal ileal involvement. Stool cultures and C. difficile were negative. CRP was 154.9 mg/L and fecal calprotectin was 1710 mcg/g. Colonoscopy showed patchy erythema and aphthous ulcers in the colon. Terminal ileal biopsies showed crypt architectural distortion and patchy acute inflammation. She started on infliximab therapy. Her diarrhea resolved prior to treatment, with no clinical improvement of her arthritis. Conclusions IL-17 inhibitors are effective in the treatment of PsO, PsA, and AS, however, in all cases described, it is unclear whether IL-17 inhibition led to new-onset IBD, or an exacerbation of previously asymptomatic IBD. Patients being considered for IL-17 inhibition with baseline gastrointestinal symptoms should be investigated for IBD. Funding Agencies None