RO7790121, an antibody against tumour necrosis factor-like ligand 1A (Anti-TL1A), helps improve the health-related quality of life (HR-QoL) for patients with moderately to severely active ulcerative colitis (UC), as shown in the phase IIb TUSCANY-2 trial.

RO7790121 has been shown to be associated with meaningful improvements in clinical and endoscopic endpoints. In the intention-to-treat population, higher percentages of patients in all RO7790121 dose groups (50 mg, 150 mg, and 450 mg) achieved the primary endpoint of clinical remission by total Mayo score (tMS) during the 14-week induction period compared with those in the placebo group (25.5 percent, 23.3 percent, and 23.9 percent vs 11.6 percent, respectively), reported lead investigator Dr Andres Yarur from the Cedars-Sinai Medical Center in Los Angeles, California, US. [Clin Gastroenterol Hepatol 2021;19:2324-2332]

Notably, remission was sustained from week 14 through week 56 for patients treated with the same dose of RO7790121 during the maintenance period (from 26.1 percent to 31 percent in the 50-mg group, from 27.6 percent to 34.6 percent in the 150-mg group, and from 25 percent to 39.3 percent in the 450-mg group).

Similar results were obtained when clinical remission was defined by modified Mayo score, Yarur added.

At week 14, more patients in the 50-, 150-, and 450-mg RO7790121 groups achieved endoscopic improvement than those in the placebo group (40.4 percent, 38.3 percent, and 40.9 percent vs 18.6 percent, respectively). Patients receiving a stable RO7790121 dose throughout the maintenance period showed sustained remission at week 56 (50-mg group: from 41.3 percent to 38.1 percent; 150-mg group: from 44.8 percent to 39.3 percent; 450-mg group: from 35.7 percent to 50 percent).

Improved quality of life

In the present analysis, Yarur noted that across all RO7790121 doses, improvements in total IBDQ score were observed as early as week 4 compared with placebo. The mean change from baseline to week 4 in total IBDQ score was 33.82 (90 percent confidence interval [CI], 26.18?41.46) in the 50-mg group, 35.76 (90 percent CI, 29.13?42.4) in the 150-mg group, 35.87 (90 percent CI, 30.38?41.35) in the 450-mg group vs 16.78 (90 percent CI, 9.01?24.55) in the placebo group. These changes were sustained through week 52 for RO7790121-treated patients. [AIBD 2024, abstract S13]

Furthermore, patients who received RO7790121 experienced improvements in fatigue, abdominal bloating, and pain compared with those on placebo, he said.

During the induction period, 47.8 percent of patients overall had at least one treatment-emergent adverse event (TEAE), with the most common being anaemia (5.3 percent) and headache (5.3 percent). A total of 10 patients had serious TEAEs, including three in the 50-mg group, three in the 450-mg group, and four in the placebo group. One serious TEAE each in the 450-mg and placebo groups were related to treatment. TEAEs led to treatment discontinuation in six patients.

Yarur emphasized that the safety profile of RO7790121 during the induction period was similar to that observed during the maintenance period. None of the patients died during the trial.

The analysis included 245 adult patients (mean age 40.7 years, 40.4 percent female, mean BMI 24.4 kg/m²) with moderately to severely active UC, including 47 in the 50-mg group, 62 in the 150-mg group, 91 in the 450-mg group, and 45 in the placebo group. Of the patients, 228 completed the induction phase and 224 entered the maintenance phase.

“RO7790121 is a fully human monoclonal antibody against TL1A that prevents the binding of TL1A to DR3 expressed on immune cells and fibroblasts, therefore targeting pathways of inflammation and fibrosis in inflammatory bowel disease,” Yarur said.

“Confirmatory phase III studies (NCT06589986 and NCT06588855) are currently ongoing,” he added.