Ustekinumab in Treatment of Crohnʼs Disease Patients with Refractory Disease: Case Series

Abstract

Purpose: Purpose: Interleukin-12 and interleukin-23 are inflammatory cytokines involved in Crohn's disease pathophysiology. Ustekinumab is a monoclonal antibody against the p40 subunit of interleukin-12/23 and may be effective in treatment of Crohn's disease. We report a series of 3 cases of moderate to severe Crohn's disease refractory to standard therapy treated with Ustekinumab. Case Presentation: Patient 1: 40 yo woman with severe ileo-colonic Crohn's disease, right colonic resection and severe diarrhea, abdominal pain and subjective fevers while on maintenance treatment with certolizumab. She previously failed 5-aminosalisilates, 6-MP, prednisone, mycophenalate, infliximab, adalimumab and certolizumab. Colonoscopy showed severe disease in the rectosigmoid. A loading dose of 90 mg of Ustekinumab led to significant improvement of symptoms: bowel movements decreased (3/day), stool consistency increased and abdominal pain improved. Repeat colonoscopy showed significant resolution of inflammation in the rectum and sigmoid. Patient is currently on maintenance dose of Ustekinumab 90mg at 12 weeks. Patient 2: 31 yo women with Crohn's disease diagnosed at age 16; failed multiple therapies including 5-aminosalicylates, methotrexate, 6-mercatopurine, infliximab, adalimumab, certolizumab, and natalizumab. Patient received Ustekinumab; after the induction phase (0, 4, 12 weeks) her CDAI score improved from 376 points to 130 points and she is tapering off corticosteroid therapy. Patient 3: 30 yo man with 12 year history of small bowel Crohn's disease; difficult to control disease despite 5-aminosalycilates, corticosteroids, immunomodulators, adalinumab, certolizumab; he underwent five bowel resection for stricturing disease and continue to have significant flares while on natalizumab. He received loading dose of Ustekinumab which was followed by decreased bowel movements from 10 to 4 a day, improvement in abdominal pain and a drop in the CDAI score from 179 to 96 points. Discussion: Alternative therapy in patients with active Crohn's disease who fail to respond to conventional therapy (including anti-TNF therapy) is an important unmet clinical need. Inhibition of the interleukin-12/23 inflammation pathway via monoclonal antibody blockade of their common p40 subunit constitutes a unique mechanism of action. Although our three cases have short follow up, the data generally are consistent with a beneficial treatment effect in this refractory group of patients. Conclusion: Ustekinumab induced a clinical response in patients with moderate-to-severe Crohn's disease refractory to standard therapy and is a promising new treatment. Disclosure: Dr Uma Mahadevan-Velayos-Consultant: Centocor, Abbott, UCB, Elan.