Report of successful use of ustekinumab in Crohn’s disease refractory to three anti-TNF therapies

Autor: D. P. O’Donoghue, Denise Keegan, Glen A. Doherty, Zaid Heetun
Rok vydání: 2014
Předmět:
Zdroj: Irish Journal of Medical Science (1971 -). 183:507-508
ISSN: 1863-4362
0021-1265
DOI: 10.1007/s11845-014-1107-2
Popis: Gene association studies highlighting the association between IL-23 receptor polymorphism and IBD [1] have stimulated much interest in targeting of Th17 signalling as part of therapy. Ustekinumab is a monoclonal antibody directed against the shared p40 subunit of IL-12 and IL-23. An initial RCT of ustekinumab in Crohn’s disease failed to definitively demonstrate effectiveness [2]. Subgroup analysis suggests that ustekinumab may be effective in patients with a raised CRP who have previously received infliximab [3]. We present the case of a 53-year-old gentleman diagnosed with Crohn’s disease in 1983. He underwent early colectomy with end-ileostomy for medically refractory disease. He experienced persistent disease activity with very significant cumulative corticosteroid use and developed progressive penetrating complications with multiple enteroenteric, enterocutaneous and enterovesical fistulae, requiring several laparotomies. He did not experience any therapeutic benefit to either azathioprine or mercaptopurine. He was a primary non-responder to infliximab and adalimumab. He remained steroid dependent to control his symptoms of abdominal pain and high-output ileostomy. He developed progression of disease in 2010 with pyloric involvement resulting in gastric outlet obstruction. His weight fell from 61 to 50 kg between February and June 2010. He was judged unsuitable for a gastrojejunostomy due to his extensive surgical history (frozen abdomen). His symptoms worsened despite use of high-dose steroids, ciclosporin and subsequently combination certolizumab and methotrexate. He also underwent five sessions of pyloric stricture dilatation and placement of two temporary metal stents with limited success. His albumin fell from 25 to 14 g/dL (normal range 35–45 g/dL) in Jan 2011. Ustekinumab was commenced as an unlicensed therapy in February 2011 (with discontinuation of methotrexate and certolizumab). He received induction at weeks 0, 1, 2, 3 at 90 mg subcutaneously (s/c) as per the Sandborn et al. [2] induction regimen. His weight increased from 49 kg (at initiation of induction) to 53 kg at end of induction. His albumin correspondingly rose from 14 to 20 g/dL with a decrease in the C-reactive protein (CRP) from 37.2 to 3.4 mg/L (normal range \ 5mg/L) during the same timeframe. A maintenance regimen of ustekinumab at 45 mg s/c every month was then initiated. Corticosteroids were then weaned gradually and eventually discontinued in May 2011. He has remained symptomatically well and has not required further steroids. The patient’s weight has continued to increase (see Fig. 1) despite steroid withdrawal. CRP remains suppressed at 3.8 g/dL. He required only three further sessions of pyloric stricture dilatation. He remains steroid free and in remission at more than 12-month follow-up. This is the first documented case of successful induction and maintenance of remission of Crohn’s disease by ustekinumab in a patient who has failed all three anti-TNF agents. Z. S. Heetun (&) D. Keegan D. O’Donoghue G. A. Doherty Centre for Colorectal Disease, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland e-mail: heetunz@gmail.com
Databáze: OpenAIRE
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