Comparative Efficacy of Mirikizumab Versus Azathioprine and Glucocorticoids in Newly Diagnosed Moderate-to-Severe Ulcerative Colitis: A 52-Week Randomized Trial

The primary objective is to evaluate the efficacy of mirikizumab induction and maintenance therapy compared to azathioprine and glucocorticoids in achieving comprehensive disease control at Week 52 in patients with newly diagnosed moderate-to-severe ulcerative colitis. In the comparator arm, any requirement for step-up treatment is defined as a failure of response. 5

The sponsor did not provide information regarding the total number of participants. The study population consists of patients diagnosed with ulcerative colitis. Eligible participants include both males and females within the age range of 18 to 75 years. The cohort is characterized by early disease, defined as a duration of less than 12 months since the initial diagnosis, with moderate-to-severe activity. Selection is based on a modified Mayo score between 5 and 9, an endoscopic Mayo score of 2 or greater, and a Robarts Histopathology Index greater than 4. Participants must demonstrate elevated C-reactive protein or fecal calprotectin levels. Inclusion requires that patients are naïve to azathioprine, its metabolite 6-mercaptopurine, and advanced therapies. Relevant medical history includes ongoing 5-aminosalicylic acid therapy for at least 8 weeks and stable oral steroid therapy for at least 2 weeks. The disease must involve the rectum and sigmoid colon.

This 52-week, multicenter, open-label, randomized controlled trial evaluates the efficacy of top-down therapy for patients with newly diagnosed moderate-to-severe ulcerative colitis. Participants are randomized to receive either mirikizumab via intravenous or subcutaneous administration or a comparator regimen consisting of oral azathioprine and glucocorticoids. The study assesses the proportion of patients achieving comprehensive disease control at Week 52. The clinical protocol involves a screening period to verify eligibility based on modified Mayo score, endoscopic Mayo score, Robarts Histopathology Index, and biochemical markers such as C-reactive protein or fecal calprotectin. Following enrollment, participants undergo scheduled assessments including endoscopy and daily diary entries through the end-of-study visit. In the comparator arm, any requirement for step-up treatment is classified as a failure of the primary endpoint. The total duration of participant involvement is approximately one year.

The experimental treatment consists of mirikizumab administered via two different routes. The induction phase involves intravenous administration of 300 mg. Maintenance therapy is provided through subcutaneous injection of 200 mg.

The comparator therapy involves standard of care using azathioprine and glucocorticoids. Azathioprine is administered in the oral form at a dosage of 2.5 mg/kg. Glucocorticoids are administered orally at a dose of 60 mg.

The primary efficacy endpoint is the proportion of patients achieving comprehensive disease control at Week 52. This assessment is utilized to evaluate the efficacy of mirikizumab induction and maintenance therapy compared to azathioprine and glucocorticoids in patients with newly diagnosed moderate-to-severe ulcerative colitis. In the comparator arm, any step-up treatment administered at any time point is classified as non-response.