Head-to-head data comparing biologic and small molecule therapies for the treatment of ulcerative colitis are limited and the optimal sequencing of these options is unknown, Frank Scott, MD, said at the Crohn’s & Colitis Congress on January 22.

In his presentation of a study in which he and his colleagues “endeavored to identify the most effective clinical treatment algorithm” for positioning treatments for moderate to severe UC, Dr Scott said, the use of vedolizumab as first-line therapy came out ahead.

Dr Scott is an assistant professor of medicine in the Division of Gastroenterology and Hepatology at the University of Colorado in Aurora.

In this study, Dr Scott and colleagues used a Markov simulation model to determine which treatment could yield the greatest quality adjusted life years (QALYs) over 1 year. This simulation considered 4 therapies: infliximab with azathioprine, tofacitinib, ustekinumab, and vedolizumab. These therapies were then combined into 8 potential treatment algorithms. The least desirable option was colectomy, Dr Scott said.

Session moderator Millie Long, MD, pointed out that insurers often require adalimumab be used as first-line therapy. Dr Scott explained that using this same model, when incorporating adalimumab as first-line therapy for all the 8 branches, “the adalimumab as first-line therapy branch that performed best out of those 8 branches underperformed all 8 of the algorithms that are presented [that did not included adalimumab].”

For each medication in the model, simulated patients had the possibility of entering remission or response, developing a severe adverse event or infection, or losing response to the therapy. “If individuals experienced nonresponse, or loss of response, or a serious adverse event,” Dr Scott explained, “they moved on to the next medication in their specific treatment algorithm.” The base patient of the model was a 35-year-old male with moderate-to-severe UC who was naïve to biologics and immunomodulators. The transition probabilities for response, remission, and adverse event rates were derived from relevant clinical trials, such as ACT 1/2, GEMINI, UNIFI, and OCTAVE. For lymphoproliferative risks, researchers used age-specific Surveillance, Epidemiology, and End Results (SEER) data and treatment-specific risks from CESAME. The authors wrote, “Primary analyses consisted of first order Monte Carlo simulation of 100 trials of cohorts consisting of 100,000 individuals.”

Researchers found that algorithms that used vedolizumab as first-line therapy had the greatest quality of life and proportion of patients in remission at 1 year, in comparison to the algorithms using either infliximab with azathioprine or ustekinumab as the first line. The algorithm with the greatest quality of life advantage over all was vedolizumab followed by infliximab with azathioprine, then ustekinumab, and finally tofacitinib, which had a benefit of 0.008 to 0.011 QALYS at 1 year over the other options. Dr Scott stated, “The least preferred strategies were those where ustekinumab were used as first-line therapy.”

Through Markov strategies, the researchers also estimated the percentage of the cohort that was in steroid-free remission at the end of 1 year. Dr Scott said, “The vedolizumab as first-line therapy algorithms yielded 43% to 47% of their population in steroid-free remission at 1 year.”

The authors noted that “further analyses assessing model inputs, probabilistic analyses, and strategy cost-effectiveness are required.”

—Allison Casey

Reference:

Scott FI, Afzali A, Dulai PS, et al. Identifying the most effective treatment algorithm for therapies to treat moderate to severe ulcerative colitis. Abstract presented at: Crohns & Colitis Congress. January 22, 2022. Virtual.