Clin Gastroenterol Hepatol. 2020 Aug 12;S1542-3565(20)31130-7.doi: 10.1016/j.cgh.2020.08.021. Online ahead of print.

Frank I Scott ¹, Amneet K Hans ², Mark E Gerich ³, Blair Fennimore ³, Ronac Mamtani ⁴, Ravy K Vajravelu ⁵, James D Lewis ⁵

Author information

• ¹Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora CO; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA. Electronic address: frank.i.scott@ucdenver.edu.
• ²Division of Digestive Diseases, Emory University School of Medicine, Atlanta GA.
• ³Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora CO.
• ⁴Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA.
• ⁵Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA; Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA.

Abstract

Background & aims: Ustekinumab is a monoclonal antibody against interleukin 12 and interleukin 23 that has been approved by the Food and Drug Administration for treatment of Crohn's disease (CD). We sought to identify the ideal position for ustekinumab in treatment algorithms for CD.

Methods: We constructed a Markov model to identify an optimal treatment sequence for CD that included ustekinumab for 1 year or more. The base case was a 35-year old male with moderate to severe CD who had not previously received biologic or immunomodulator therapy. The standard of care treatment algorithm was defined as initial therapy with infliximab and azathioprine, followed by adalimumab and azathioprine, vedolizumab, and lastly surgical resection. The model assessed positions for ustekinumab before standard of care, ustekinumab after infliximab and azathioprine but before the remaining treatments, after infliximab, azathioprine, and adalimumab but before vedolizumab and surgery, or after the other biologics but before surgery. We derived transition probabilities and quality adjusted life years (QALYs) from relevant trials, observational studies, and time trade-off analyses. Primary analyses consisted of first order Monte Carlo simulation of 100 trials of cohorts of 100,000 individuals.

Results: Ustekinumab as first-line therapy yielded the greatest QALYs (incremental effectiveness, 0.016-0.020 QALYs), resulting in 10% more patients in remission or response, and 2% fewer surgeries at 1 year, compared with other algorithms. The model was not sensitive to 25% variation in transition probabilities.

Conclusions: In a simulation based on a 35-year old male patient with moderate to severe CD, we found that ustekinumab as the first-line biologic therapy yields greater QALYs at the end of 1 year than compared with use later in the CD treatment algorithm.