Introduction
Mirikizumab (MIRI) is an anti-IL-23p19 antibody with demonstrated efficacy compared to placebo (PBO) in the treatment of moderately-to-severely active ulcerative colitis (UC) (LUCENT-1: NCT03518086; LUCENT-2: NCT03524092).1 Prevention of IBD-related surgery and hospitalizations is a goal in disease-modification trials for preventing disease progression.2 We described the rates of these events in the LUCENT-1 and -2 trials.
Aims & Methods
Patients were randomized to intravenous MIRI 300 mg or PBO every 4 weeks (Q4W) for induction in LUCENT-1. Patients randomized to MIRI induction and achieving clinical response at Week (W)12 were re-randomized 2:1 in LUCENT-2 to subcutaneous MIRI 200 mg Q4W or PBO (MIRI withdrawal) for maintenance (W12-52). Descriptive statistics were used for proportion of patients in LUCENT-1 and -2 who had hospitalization and/or surgery by treatment group and the exposure-adjusted incident rate (IR). For LUCENT-1, hospitalizations in the induction period and surgeries during the induction and 16-week follow-up period were included. For LUCENT-2, all events were from the on-treatment period. Only hospitalizations associated with an adverse event with ≥24-hour stay (for any causes) were recorded.
Results
MIRI-treated patients had significantly lower IR of overall hospitalization, UC-related hospitalization, and overall surgery vs PBO-treated patients in LUCENT-1 (IR ratio MIRI vs PBO: 0.4, 0.1, 0.4, respectively). IR of UC-related surgery was 1.3 per 100 patient-years in MIRI-treated patients vs 2.6 per 100 patient-years in PBO group (Table). Mean time to first surgery or hospitalization from randomization was 30.5 days for PBO and 58.7 days for MIRI. Additional analyses revealed that patients on MIRI who had surgery/hospitalization in LUCENT-1 or -2 tended to have prior biologic failure and longer duration of disease. Similarly, in LUCENT-2, MIRI-treated patients had significantly lower IR of all-cause hospitalization and similar all-cause surgery vs PBO. No UC-related hospitalization and surgery were reported in the MIRI group while 2 UC-related hospitalizations (1.8 per 100 person-years) were reported from PBO.
Hospitalization and Surgery Rates in LUCENT-1 and LUCENT-2
|
|---|
Note: * represent p<0.05.
IR = incidence rate; IRR = incidence rate ratio; MIRI = mirikizumab; N = number of patients in the analysis population; n = number of patients within each specific category; N/A= not applicable; PBO = placebo; PYE = patient years of exposure; PYR = patient years at risk; UC = ulcerative colitis.
a The IR and IRR confidence intervals and the p-values are based on a Poisson distribution
b UC-related surgeries are total colectomy, partial colectomy, and proctocolectomy.
|
LUCENT-1
| LUCENT-2
|
| MIRI 300mg (N=868, PYE=201.0) | PBO (N=294, PYE=65.8)
| MIRI vs. PBO
| MIRI 200mg (N=365, PYE=267.9)
| PBO (N=179, PYE=111.0) | MIRI vs. PBO
|
| Events, n(%) | PYR | Incidence rate, per-100 py (95%CI)a | Events, n(%)
| PYR
| Incidence rate, per-100 py (95%CI)a
| IRR (95% CI) | Events, n(%)
| PYR
| Incidence rate, per-100 py (95%CI)a
| Events, n(%)
| PYR
| Incidence rate, per-100 py (95%CI)a
| IRR (95% CI)
|
| Overall hospitalization | 21 (2.4) | 199.7 | 10.5 (6.5, 16.1) | 16 (5.4) | 64.6 | 24.8 (14.1, 40.2) | 0.4 (0.2, 0.8)* | 10 (2.7) | 264.9 | 3.8 (1.8, 6.9) | 11 (6.1) | 109.0 | 10.0 (5.0, 17.9) | 0.4 (0.2, 0.9)* |
| UC-related hospitalization | 3 (0.3) | 200.9
| 1.5 (0.3, 4.4)
| 10 (3.4)
| 65.2 | 15.3 (7.4, 28.2) | 0.1 (0.0,0.4)* | 0 | 267.9 | 0 (0.0, 1.4) | 2 (1.1) | 110.7 | 1.8 (0.2, 6.5) | 0 |
| Overall surgery | 11 (1.3) | 227.9
| 4.8 (2.4, 8.6)
| 9 (3.1)
| 75.8 | 11.9 (5.4, 22.5) | 0.4 (0.2,1.0)* | 13 (3.6) | 263.2 | 4.9 (2.6, 8.4) | 5 (2.8) | 109.5 | 4.6 (1.5, 10.7)
| 1.1 (0.4, 3.0) |
| UC-related surgeryb | 3 (0.3) | 228.6
| 1.3 (0.3, 3.8)
| 2 (0.7)
| 76.8 | 2.6 (0.3, 9.4)
| 0.5 (0.1, 3.0) | 0 | 267.9 | 0 (0.0, 1.4)
| 0 | 111.0 | 0 (0.0, 3.3) | N/A |
Conclusion
Lower rates of UC-related hospitalizations and UC-related surgery were observed in patients treated with MIRI compared to those treated with PBO during the 12W induction LUCENT-1, and that impact continued through the 40W of maintenance LUCENT-2 with no UC-related hospitalizations or UC-related surgery reported in MIRI-treated patients.
References
1. D’Haens G, et al. Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis. New England Journal of Medicine 2023;388(26):2444-2455.
2. Le Berre C, Peyrin-Biroulet L. Selecting End Points for Disease-Modification Trials in Inflammatory Bowel Disease: the SPIRIT Consensus From the IOIBD. Gastroenterology 2021;160(5):1452-1460.e21.
Disclosure
MR serves as a consultant and on advisory boards for AbbVie, Janssen, Bristol-Myers Squibb, UCB, Takeda, Pfizer, Prometheus Laboratories, Lilly, Celgene, and Amgen.
LPB has served as a consultant for AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax; he received grants from Takeda, Fresenius Kabi, Celltrion; he served as a speaker for Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Lilly, Gilead, Viatris, Medac; he also declares support travel by Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Celltrion, Takeda, Pfizer, Gossamer Bio, Sandoz, MSD, Amgen, Lilly, Gilead, Thermo Fisher, Medac, CONNECT Biopharm; he declares stock options of Clinical trials Mobile Application.
JW, BZ, IR, KT, CO are employees and minor shareholders of Eli Lilly and Company.
SN has served on advisory board and speaker for Eli Lilly and Company, Pfizer and advisory board for madrigal and speaker for Janssen
TK has served as a paid consultant for Abbvie, Amgen, Biogen, Mundipharma, Hospira, Gilead, Janssen, Pfizer, MSD Sharp & Dome GmbH, and Novartis. He has received reimbursement of meeting participation fees and of travel and accommodation expenses from Abbvie, Janssen, MSD, and Takeda. He has received honoraria for preparing continuing medical education events from Abbvie, Falk, Janssen, MSD, Takeda, and Ferring Arzneimittel GmbH.
LM reports educational grants from Abbvie, Janssen, Pfizer and Takeda; advisory boards: AbbVie, Bristol Myers Squibb, Janssen, and Celltrion; consultant for Abbvie, Pfizer and Pharmacosmos.
FM has served as a speaker and received honoraria from Merck Sharp & Dohme, Abbvie, Vifor, Falk, Laboratorios Vitoria, Ferring, Hospira, and Biogen.
