P055 Development of Crohn's disease with use of secukinumab

Abstract

BACKGROUND: Secukinumab is an anti-IL-17a monoclonal antibody approved for the treatment of ankylosing spondylitis, plaque psoriasis, and psoriatic arthritis. IL-17 has been associated with both pro- and anti-inflammatory properties. Mice studies suggest a beneficial role of IL 17a in the gut, as its inhibition reduces the recruitment of neutrophils, resulting in gut inflammation. Hueber et al. (2012) conducted a RCT of secukinumab in patients with moderate to severe CD, which was terminated prematurely due to worsening of Crohns symptoms, other adverse events, and lack of efficacy. We present an interesting case of IL-17 blockade induced inflammatory bowel disease. CASE: A 36-year-old male with history of refractory psoriasis most recently treated with secukinumab presented to the ED with complaint of abdominal bloating, fever, lower extremity lesions and diarrhea ×14 days. He was previously treated with methotrexate, etanercept, ustekinumab and adalimumab. Secukinumab was started 2 years before presentation, but was held in the setting of abnormal LFTs. A chronic liver disease workup was negative including a non-diagnostic liver biopsy. He restarted secukinumab approximately 7 months prior to his presentation. Patient presented with diarrhea for the preceding 2 weeks, consisting of at least 5 loose, non-bloody BMs per day. He also noted several lesions on his lower extremity for which his dermatologist obtained biopsy, consistent with erythema nodosum. He noted no prior history of any gastrointestinal symptoms and no family history of IBD. At the time of evaluation examination was notable for mild abdominal distention and right sided tenderness without guarding. Workup included mild leukocytosis at 11,700 with left shift, CRP 255, stool studies negative for c. diff, fecal lactoferrin was positive. A diagnostic colonoscopy was performed and there was evidence of severe colitis with stellate ulcers and friability involving the right colon extending through the transverse colon. The terminal ileum, left colon and rectum were spared. Biopsy demonstrated chronic colitis with markedly active ulceration and the patient was discharged on a prednisone taper. A colonoscopy was repeated 1 month after his prednisone was tapered, and there was evidence of scarring and pseudopolyps, but no inflammation. Biopsies demonstrated inactive chronic colitis. Given clinical and endoscopic remission, he was monitored off biologic therapy specifically for IBD. He was started on guselkumab, an anti-IL-23 agent, for his psoriasis. Ten months later, he remains in clinical remission with an undetectable fecal calprotectin. DISCUSSION: Our case provides a challenging dilemma regarding secukinumab and whether use led to unmasking of a subclinical IBD, induction of denovo IBD, or development of a drug-induced colitis. We suspect that the inhibition of IL-17a initiated an inflammatory cascade that led to the development of Crohn's disease, and the presence of extra intestinal manifestation (biopsy proven erythema nodosum) supports this. Our case serves to raise awareness that use of secukinumab can lead to IBD. All providers should have a high index of suspicion for the development or unmasking of IBD with use of secukinumab, and use caution in those with genetic susceptibility.