LUCENT trials: Mirikizumab works in UC, regardless of targeted therapy history

Mirikizumab outperformed placebo for efficacy endpoints in participants with moderately to severely active ulcerative colitis (UC), irrespective of the number and types of failed prior targeted therapies. This was the key finding of research into the data of the LUCENT-1 induction study and LUCENT-2 maintenance trial.

Prof. Silvio Danese (Vita-Salute San Raffaele University, Italy) assessed the efficacy of mirikizumab, a humanised monoclonal antibody against IL-23p19, in participants with moderately to severely active UC based on the number and types of failed targeted immunomodulators [1]. The investigators examined the influence of prior use of TNF inhibitors, vedolizumab, and tofacitinib. Participants from the LUCENT-1 study (NCT03518086; n=1,162) who responded to mirikizumab induction therapy at week 12 were re-randomised to mirikizumab or placebo through week 52 in the LUCENT-2 trial (NCT03524092; n=544). Among other endpoints, clinical response was evaluated, which was defined as a decrease in the modified Mayo score of ≥30% and ≥2 points from baseline, a decrease of ≥1 point in the rectal bleeding subscore (RBS) or an RBS of 0 or 1. At baseline, 683 participants were targeted immunomodulator-naïve, 245 had failed 1 prior advanced therapy, and 234 had failed 2 or more targeted immunomodulators. In addition, 36.3% of the participants failed TNF inhibitors, 18.8% failed vedolizumab, and 15.2% failed a TNF inhibitor plus 1 other agent, either vedolizumab or tofacitinib.

At week 12, a higher percentage of immunomodulator-naïve participants achieved clinical response with mirikizumab compared with placebo (69.8% vs 50.6%; P<0.001). The same findings were observed for the other subgroups when compared with placebo, including for participants who failed 1 prior therapy (63.9% vs 36.9%; P<0.001) and those who failed 2 or more therapies (45.3% vs 20.8%; P<0.001). Regarding the type of targeted therapy, a higher percentage of participants who previously failed TNF inhibitors achieved clinical response compared with placebo (54.2% vs 26.8%; P<0.001). The same trend was found for participants who failed vedolizumab or TNF inhibitor plus another agent.

Similar trends were observed for other efficacy endpoints, namely, symptomatic remission, clinical remission, and endoscopic remission. Importantly, these results were consistent for the maintenance population at week 52.

In short, mirikizumab outperformed placebo in participants with UC across all efficacy endpoints, as an induction or maintenance therapy, irrespective of the number and types of failed advanced therapies.

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   1. Navabi S, et al. Effect of mirikizumab on clinical and endoscopic outcomes based on prior advanced therapy failure in patients with moderately to severely active ulcerative colitis. OP040, UEG Week 2023, 14–17 October, Copenhagen, Denmark.

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Posted on 7 December 20238 April 2024