Novel Drug Maintained Clinical Improvements in IBD

Patients with inflammatory bowel disease (IBD) who initially responded to the investigational monoclonal antibody tulisokibart continued to maintain clinical and endoscopic improvements through week 50, according to data from open-label extensions of a pair of phase II trials.

In patients with ulcerative colitis, 48% of those receiving 250 mg of intravenous tulisokibart achieved clinical remission — defined as an endoscopic subscore of 0 or 1, a rectal bleeding subscore of 0, and a stool frequency subscore of 0 or 1 that was not higher than baseline — compared with 32% of those receiving 100 mg, reported Christopher Ma, MD, MPH, of the University of Calgary in Canada.

In patients with Crohn’s disease, 56% of those receiving 250 mg of tulisokibart achieved clinical remission — defined as a Crohn’s Disease Activity Index (CDAI) score below 150 — compared with 48% of those in the 100-mg group, reported Brian Feagan, MD, MSc, of Western University in London, Ontario, Canada.

The findings were presented at the United European Gastroenterology Week in Vienna, and both Ma and Feagan noted that tulisokibart was well tolerated with no identified safety signals.

The randomized phase II ARTEMIS-UC trial previously showed that significantly more patients with moderately to severely active ulcerative colitis achieved clinical remission with tulisokibart compared with placebo. The new data come from an extension of that trial, and another phase II trial, APOLLO-CD, which includes patients with Crohn’s disease.

The mechanism of tulisokibart — a tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody — works differently than currently approved drugs for ulcerative colitis and Crohn’s disease.

The findings of these studies are encouraging, Audrey Bennett, MD, of Vanderbilt University Medical Center in Nashville, Tennessee, told MedPage Today.

“There are several different inflammatory pathways involved in ulcerative colitis and Crohn’s disease, but currently we do not have the ability to predict which medication will be most effective for an individual patient,” said Bennett, who was not involved in either study.

“Despite there being several advanced therapies available for ulcerative colitis and Crohn’s disease, some patients never respond to a medication, or lose response and continue to have significant ongoing symptoms,” she added. “The addition of new therapies with novel mechanisms of action helps add to the armamentarium in caring for patients living with inflammatory bowel disease in a hope to find a therapy that will be effective.”

The ARTEMIS-UC trial initially enrolled two cohorts of patients with moderately to severely active ulcerative colitis, the smaller of which included only participants who tested positive for a likely response to tulisokibart. After the 12-week induction period, participants could opt to continue in the extension, which runs until week 170. The newly presented extension data include tulisokibart responders from the larger cohort of patients — those enrolled independent of the results from their genetic test for drug response — through week 50.

Of the 68 patients who responded to tulisokibart during induction, 47 continued in the trial and received open-label intravenous tulisokibart every 4 weeks starting at week 14. Among the 25 patients who received 250 mg of tulisokibart, 48% showed endoscopic improvement — an endoscopy subscore of 1 or less with no friability — compared with 36% of the 22 patients who received 100 mg.

Clinical response occurred in 68% of those in the 250-mg group and in 59% of those in the 100-mg group. Symptomatic remission occurred in 32% and 23%, respectively.

Adverse events, which were mostly mild to moderate, occurred in 63% of patients receiving 250 mg and in 77% of patients receiving 100 mg. One patient receiving 250 mg and two patients receiving 100 mg experienced serious adverse events.

In the APOLLO-CD trial extension, 53 of 55 patients completed the 12-week induction period. Of the 37 participants who responded, 19 were randomly assigned to receive 100 mg and 18 received 250 mg. About twice as many of the 250-mg group (44%) as the 100-mg group (21%) had never previously received a biologic drug for Crohn’s.

Similar to the ulcerative colitis trial extension findings, clinical, endoscopic, and biomarker outcomes were maintained at both doses in the Crohn’s patients through week 50, but improvement was greater in the 250-mg group. Clinical response occurred in 67% of patients receiving the higher dose and 58% of those receiving the lower dose. Endoscopic response occurred in 28% and 16%, respectively, and composite endoscopic and clinical response occurred in 22% and 16%.

Normalization of high-sensitivity C-reactive protein was assessed in 25 participants; none of the nine patients receiving 100 mg achieved normalization compared with 31% of the 16 patients receiving 250 mg.

Mostly mild-to-moderate adverse events occurred in 78% of participants during the 12-week induction and in 83% and 84% of the 250-mg and 100-mg groups, respectively, at week 50. Urinary tract infection, COVID-19, upper respiratory tract infection, bronchitis, Clostridium difficile infection, and influenza occurred most frequently — in at least 10% of patients in either group. Serious adverse events occurred in 6% of the high-dose group and 11% of the low-dose group.

Tulisokibart will next be tested in phase III trials for ulcerative colitis and Crohn’s disease.

“It seems reasonable to anticipate that a phase III trial will show similar results,” Bennett said. “It will be interesting to see the outcomes in a larger cohort of patients.”