Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis

Abstract

BACKGROUNDMirikizumab, a p19-directed antibody against interleukin-23, showed efficacy in the treatment of ulcerative colitis in a phase 2 trial. METHODSWe conducted two phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab in adults with moderately to severely active ulcerative colitis. In the induction trial, patients were randomly assigned in a 3:1 ratio to receive mirikizumab (300 mg) or placebo, administered intravenously, every 4 weeks for 12 weeks. In the maintenance trial, patients with a response to mirikizumab induction therapy were randomly assigned in a 2:1 ratio to receive mirikizumab (200 mg) or placebo, administered subcutaneously, every 4 weeks for 40 weeks. The primary end points were clinical remission at week 12 in the induction trial and at week 40 (at 52 weeks overall) in the maintenance trial. Major secondary end points included clinical response, endoscopic remission, and improvement in bowel-movement urgency. Patients who did not have a response in the induction trial were allowed to receive open-label mirikizumab during the first 12 weeks of the maintenance trial as extended induction. Safety was also assessed. RESULTSA total of 1281 patients underwent randomization in the induction trial, and 544 patients with a response to mirikizumab underwent randomization again in the maintenance trial. Significantly higher percentages of patients in the mirikizumab group than in the placebo group had clinical remission at week 12 of the induction trial (24.2% vs. 13.3%, P<0.001) and at week 40 of the maintenance trial (49.9% vs. 25.1%, P<0.001). The criteria for all the major secondary end points were met in both trials. Adverse events of nasopharyngitis and arthralgia were reported more frequently with mirikizumab than with placebo. Among the 1217 patients treated with mirikizumab during the controlled and uncontrolled periods (including the open-label extension and maintenance periods) in the two trials, 15 had an opportunistic infection (including 6 with herpes zoster infection) and 8 had cancer (including 3 with colorectal cancer). Among the patients who received placebo in the induction trial, 1 had herpes zoster infection and none had cancer. CONCLUSIONSMirikizumab was more effective than placebo in inducing and maintaining clinical remission in patients with moderately to severely active ulcerative colitis. Opportunistic infection or cancer occurred in a small number of patients treated with mirikizumab. (Funded by Eli Lilly; LUCENT-1 and LUCENT-2 ClinicalTrials.gov numbers, NCT03518086 and NCT03524092, respectively.

Ulcerative Colitis in Adults

“…In the maintenance trial, LUCENT 2 (N = 544), 49.9% of patients receiving mirikizumab achieved clinical remission at week 40 vs 25.1% of those receiving placebo ( P < .001) . Adverse events, such as nasopharyngitis and arthralgia, were more frequent in the active group than the placebo group . Opportunist infection and cancer occurred in a small number of people receiving mirikizumab in the randomized trial …”

“…LUCENT 1 (N = 1162) was an induction trial demonstrating clinical remission at week 12 among 24.2% of patients receiving mirikizumab vs 13.3% receiving placebo ( P < .001) . In the maintenance trial, LUCENT 2 (N = 544), 49.9% of patients receiving mirikizumab achieved clinical remission at week 40 vs 25.1% of those receiving placebo ( P < .001) . Adverse events, such as nasopharyngitis and arthralgia, were more frequent in the active group than the placebo group .…”

“…LUCENT 1 induction trial (N = 1162). Clinical remission at wk 12: 24.2% with mirikizumab (300 mg every 4 wk x 3 doses) vs 13.3% with placebo, P < .001 …”

“…Treatment goals include inducing clinical remission (ie, induction) and preventing future flares of disease activity (ie, maintenance) . The Table describes the classes of medications used for induction and/or maintenance of UC including dose and administration, efficacy data, and safety considerations. Drugs in different classes have been developed because a number of patients do not respond to drugs and/or lose response over time.…”

“…Mirikizumab is a monoclonal antibody against the p19 subunit of IL-23 (Figure 1). LUCENT 1 (N = 1162) was an induction trial demonstrating clinical remission at week 12 among 24.2% of patients receiving mirikizumab vs 13.3% receiving placebo ( P < .001) . In the maintenance trial, LUCENT 2 (N = 544), 49.9% of patients receiving mirikizumab achieved clinical remission at week 40 vs 25.1% of those receiving placebo ( P < .001) .…”