Introduction
In October 2023, the FDA approved mirikizumab-mrkz (Omvoh) for the induction and maintenance treatment of moderate to severe ulcerative colitis (UC) in adults.1 Ulcerative colitis is a type of inflammatory bowel disease characterized by inflammation of the mucosal tissues throughout the colon and rectum. The most common symptoms resulting from UC are bloody diarrhea, increased stool frequency and urgency, and pain in the abdominal region.2,3 In addition to some of the physiologic changes in patients with UC, various quality-of-life measures are negatively affected.4
Milder forms of UC may be conventionally treated with medications like aminosalicylates, immunomodulators, or corticosteroids. However, more severe cases of UC often require biologic therapies to obtain and maintain clinical remission. Additional therapies for moderate to severe UC include small-molecule drugs like Janus kinase inhibitors and sphingosine 1-phosphate receptor modulators. Biologics can be used for extended periods as maintenance therapy, but patients can have multiple treatment failures. Therefore, new treatments with different mechanisms for moderate to severe UC are needed.3,5
Mechanism of Action
Mirikizumab-mrkz is a humanized IgG4 monoclonal antibody that binds to the p19 subunit of interleukin-23 (IL-23). Interleukin-23 is a cytokine that is important in the signaling of certain T cells and innate immune cells involved in the chronic inflammatory process of UC. The blocking of IL-23 and its signaling pathway improves UC symptoms and decreases the physiologic damage seen in the colon.6
Other inflammatory diseases including Crohn disease and plaque psoriasis use similar interleukin inhibitors. Other targets like IL-12 and the p40 subunit of IL-23 have shown efficacy in these disease states. Data suggest better disease outcomes in selectively blocking the p19 IL-23 subunit, but mirikizumab-mrkz is the first p19 IL-23 inhibitor agent approved for UC.2,7
Clinical Trials
LUCENT Program
The LUCENT program consists of three phase III clinical trials (LUCENT-1, LUCENT-2, and LUCENT-3) that evaluate mirikizumab-mrkz for the treatment of moderate to severe UC. LUCENT-1 was a short induction trial to achieve clinical remission. Patients who responded to treatment in LUCENT-1 were randomized again in LUCENT-2 to receive maintenance therapy for an additional 40 weeks. LUCENT-3 is an open-label extension of the patients in the LUCENT-2 trial who received mirikizumab-mrkz. It is scheduled to conclude in June 2025. LUCENT-3 was not included in the FDA’s recent approval of mirikizumab-mrkz, but it will be important in establishing long-term safety and efficacy data past 52 weeks.8
LUCENT-1 Trial
This phase III, double-blind, placebo-controlled, randomized trial investigated the safety and efficacy of mirikizumab-mrkz therapy to induce remission in moderate to severe UC over a 12-week period.2 It was conducted from June 2018 through January 2021 spanning across 383 locations in 34 different countries. The 1281 patients in the trial were randomized in a 3:1 ratio to receive either a mirikizumab-mrkz 300-mg intravenous (IV) infusion or placebo IV every 4 weeks for a total of three doses. Eligible patients were those for whom previous treatment with either conventional or biologic therapies had failed. Included patients also had their UC classified as moderate to severe, determined using the modified Mayo scoring system (MMS). The MMS is based on stool frequency, rectal bleeding, and endoscopic changes. Those who had prior treatment with the IL-12/23 inhibitor ustekinumab or selective IL-23 inhibitors used for other conditions were excluded.2
Mirikizumab-mrkz induction therapy achieved the primary end point of clinical remission in 24.2% of patients compared with 13.3% in the placebo group (99.875% CI, 3.2–19.1; p<0.001). Several secondary end points also showed statistical significance. Specifically, 45.5% of patients receiving mirikizumab-mrkz achieved remission of symptoms compared with 27.9% receiving placebo. Some patients reported improvement in symptoms within 3 weeks of treatment.9 In addition, many patients (63.5%) had a meaningful reduction in their modified MMS score but did not achieve clinical remission. These patients were also included in the LUCENT-2 maintenance trial.2
LUCENT-2 Trial
LUCENT-2, another phase III, randomized, placebo-controlled trial, was an extension of LUCENT-1. Instead of induction, this study evaluated the safety and efficacy of mirikizumab-mrkz as maintenance therapy for UC. Patients who had a response to mirikizumab-mrkz in LUCENT-1 were randomized in a 2:1 ratio to receive 200 mg of mirikizumab-mrkz or placebo administered subcutaneously every 4 weeks for 40 weeks. At the end of the trial, patients would have received mirikizumab-mrkz for 52 weeks between the induction and maintenance trial. The inclusion and exclusion criteria for LUCENT-2 were similar to those in the induction study.2,6
Results of the primary and several of the secondary end points can be seen in Figure 1. Almost 50% of patients achieved the primary end point of clinical remission, and 63.6% maintained their remission from induction at 52 weeks. A finding in one of the secondary end points can be visualized in section B of Figure 1. The Urgency Numeric Rating Score (NRS) did not significantly improve during the trial. However, the placebo group had a worsening of the Urgency NRS from the end of induction therapy to the end of the study.2

Figure 1. Results from the LUCENT-2 trial.2
A: Primary end point shown as “Clinical Remission.”
B: Changes in Urgency NRS throughout the induction and maintenance studies.
Adverse Effects
Table 1 lists the rates of adverse reactions seen in the LUCENT-2 maintenance trial (mirikizumab-mrkz 200-mg subcutaneous injection). The induction trial showed similar adverse effects including upper respiratory tract infections (8%) and arthralgia (2%).
Table 1. Adverse Reactions in the Group Receiving 200 mg of Mirikizumab-mrkz in LUCENT-2 (n=389)6
Adverse Reaction | Occurrence Rate (%) |
Upper respiratory tract infections | 14 |
Injection site reactions | 9 |
Arthralgia | 7 |
Rash | 4 |
Headache | 4 |
Herpes virus infections | 2 |
Special Patient Populations
According to the mirikizumab-mrkz package insert, safety data are lacking for the recommendation of use in pregnancy and lactation. Although not directly studied in humans, mirikizumab-mrkz has the potential to transfer across the placenta and into breast milk because of its IgG nature. A registry is available to monitor outcomes for pregnant patients who receive mirikizumab-mrkz.6
It is not recommended to initiate mirikizumab-mrkz in patients with liver cirrhosis present.10 Highly elevated liver enzymes and bilirubin were seen in one patient who exceeded the duration of a typical induction regimen. The concentrations returned to normal after discontinuing treatment. The risk of hepatotoxicity is rare (less than 1%), but liver enzymes and bilirubin should be monitored at baseline through at least 24 weeks of treatment.6
Infection Risk
Mirikizumab-mrkz can reduce the body’s ability to fight off infections. Patients with an active infection should not begin treatment until the infection is no longer present. Before beginning mirikizumab-mrkz treatment, testing for tuberculosis (TB) should be done to rule out a TB infection. Live vaccines are contraindicated during treatment with mirikizumab-mrkz. Patients should be up-to-date on all eligible vaccines and receive any live vaccines before beginning treatment.6
Patient Education
Patients should be educated on proper technique of the self-administered subcutaneous injections. A full subcutaneous dose requires two injections. The prefilled syringes should be stored in the refrigerator (2°C–8°C). If any of the adverse reactions listed in Table 1 or signs/symptoms of infection occur while the patient is receiving treatment, a health care provider should be notified. If hypersensitivity reactions occur, mirikizumab-mrkz should be discontinued.6
Conclusion
Mirikizumab-mrkz is the first p19 subunit anti–IL-23 antibody approved for UC. The LUCENT-1 and LUCENT-2 clinical trial data led to its approval by the FDA. These studies showed the ability of mirikizumab-mrkz to induce and maintain clinical remission up to 1 year in moderate to severe UC while having a good safety profile. The most common adverse effect are upper respiratory infections, and severe infections are rare. Storage and administration are important counseling points for patients starting treatment. Use of mirikizumab-mrkz in clinical practice has not yet been determined, but it may be an effective alternative after the failure of other agents.
References
1. Eli Lilly. FDA Approves Lilly’s OmvohTM (mirikizumab-mrkz), a First-in-Class Treatment for Adults with Moderately to Severely Active Ulcerative Colitis. Available at https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-omvohtm-mirikizumab-mrkz-first-class.
2. D’Haens G, Dubinsky M, Kobayashi T, et al. Mirikizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2023;388:2444-55. doi:10.1056/NEJMoa2207940
3. Ordás I, Eckmann L, Talamini M, et al. Ulcerative colitis. Lancet 2012;380:1606-19. doi:10.1016/S0140-6736(12)60150-0
4. Sands BE, Feagan BG, Hunter Gibble T, et al. Mirikizumab improves quality of life in patients with moderately-to-severely active ulcerative colitis: results from the phase 3 LUCENT-1 induction and LUCENT-2 maintenance studies. Crohns Colitis 360 2023;5:otad070. doi:10.1093/crocol/otad070
5. Le Berre C, Honap S, Peyrin-Biroulet L. Ulcerative colitis. Lancet 2023;402:571-84. doi:10.1016/S0140-6736(23)00966-2
6. Omvoh [package insert]. Eli Lilly, 2023.
7. Sandborn WJ, Ferrante M, Bhandari BR, et al. Efficacy and safety of mirikizumab in a randomized phase 2 study of patients with ulcerative colitis. Gastroenterology 2020;158:537-549.e10. doi:10.1053/j.gastro.2019.08.043
8. Eli Lilly. Nearly Two-Thirds of Patients Respond to Mirikizumab Treatment at 12 Weeks in Lilly’s First-in-Class Ulcerative Colitis Phase 3 LUCENT-1 Study. Available at https://investor.lilly.com/news-releases/news-release-details/nearly-two-thirds-patients-respond-mirikizumab-treatment-12.
9. Omvoh Results. 2023. Available at https://www.omvoh.com/results.
10. Mirikizumab-mrkz. In: LexiDrugs: UpToDate, 2023 [registration required]. Available at https://online-lexi-com.eu1.proxy.openathens.net/lco/action/doc/retrieve/docid/patch_f/7363529?cesid=200ifKKdU1y&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Dmirkizumab%26t%3Dname%26acs%3Dfalse%26acq%3Dmirkizumab#war.