Tulisokibart bests placebo, may yield ‘important clinical benefit’ via TL1A blockade in UC
Click Here to Manage Email Alerts
Key takeaways:
- A greater percentage of patients on tulisokibart vs. placebo achieved clinical remission at week 12.
- Researchers used a gene-based diagnostic test to identify patients with an increased likelihood of response.
Tulisokibart, an anti-TL1A monoclonal antibody, outperformed placebo in inducing clinical remission at week 12 in moderate to severe ulcerative colitis, according to a new study that also incorporated a predictive biomarker for response.
“TL1A is in the tumor necrosis factor superfamily of cytokines, is elevated in patients with inflammatory bowel disease and is directly implicated in the causation of IBD by genome-wide association studies,” Bruce E. Sands, MD, MS, Dr. Burrill B. Crohn Professor of Medicine at Icahn School of Medicine and chief of the Dr. Henry D. Janowitz Division of Gastroenterology at Mount Sinai, told Healio. “Therefore, there was a compelling reason to explore blockade of TL1A using an anti-TL1A antibody called tulisokibart in patients with UC.”
In the phase 2, multicenter, double-blind, placebo-controlled ARTEMIS-UC trial, Sands and colleagues enrolled adult patients with moderately to severely active UC who were glucocorticoid dependent or had failed treatment with conventional or advanced therapies.
The researchers administered a genetic-based diagnostic test, which identified those with a greater likelihood of response to an anti-TL1A antibody, and divided patients into two cohorts: the first with 135 patients, included regardless of test status, and the second with 43 patients who tested positive for likelihood of response.
Patients were randomly assigned to IV tulisokibart (1,000 mg on day 1 and 500 mg at weeks 2, 6 and 10) or placebo, with clinical remission assessed at week 12 in the first cohort. Patients from both cohorts with a positive test (n = 75) were combined in a separate analysis to assess the efficacy of tulisokibart in this population.
According to results published in The New England Journal of Medicine, significantly more patients on tulisokibart in the first cohort achieved clinical remission vs. placebo (26% vs. 1%; difference = 25 percentage points; 95% CI, 14-37), as well as endoscopic improvement (37% vs. 6%; difference = 31 percentage points; 95% CI, 17-43) and clinical response (66% vs. 22%; difference = 44 percentage points; 95% CI, 27-57).
“Tulisokibart had a high level of efficacy and was superior to placebo in achieving clinical remission at 12 weeks by 25%,” Sands said. “The results in the initial cohort studied suggested a higher likelihood of clinical remission in patients who tested positive for this test.”
In the analysis of positive-test patients, tulisokibart also outperformed placebo in achieving clinical remission (32% vs. 11%), with a between-group difference of 21 percentage points (95% CI, 2-38).
In both cohorts, reports of mild to moderate adverse events were similar among those treated with tulisokibart vs. placebo (46% vs. 43%).
“This phase 2 study is the first double-blinded, randomized, placebo-controlled study to demonstrate the efficacy and safety of anti-TL1A antibody in patients with moderately to severely active UC,” Sands said. “It is also the first prospective randomized controlled trial in IBD to incorporate a precision-medicine approach using a predictive biomarker for response. The results suggest that important clinical benefit may be achieved through TL1A blockade in patients with UC.”
He added: “A phase 3 program is planned to confirm these results and to further develop and confirm the precision-medicine approach.”
Collapse
Sands B, et al. N Engl J Med. 2024;doi:10.1056/NEJMoa2314076.
Click Here to Manage Email Alerts