Introduction
Mirikizumab (miri), an anti-IL-23p19 antibody, demonstrated efficacy and safety in patients with moderately-to-severely active ulcerative colitis (UC) in the Phase 3 LUCENT-1 induction1 (NCT03518086) and LUCENT-2 maintenance2 (NCT03524092) trials. Bowel urgency (BU) remission and clinically meaningful improvement (CMI) are associated with clinical response and remission.3 This analysis evaluated if the addition of BU improvement to the achievement of clinical response or remission was associated with better quality of life (QoL).
Aims & Methods
In LUCENT-1, patients were randomized 3:1 to miri 300mg intravenous or placebo every four weeks. Miri-treated patients achieving clinical response to miri at week 12 (W12) were re-randomized 2:1 to subcutaneous miri 200mg or placebo Q4W for 40 weeks in LUCENT-2 (continuous treatment up to W52). Clinical remission is based on the modified Mayo Score (MMS) and was defined as: stool frequency subscore = 0 or 1 with a ≥1-point decrease from baseline; rectal bleeding (RB) subscore = 0; endoscopic subscore = 0 or 1. Clinical response was defined as ≥2-point and ≥30% decrease in the MMS from baseline, and RB = 0 or 1, or ≥1-point decrease from baseline. Patients’ QoL was measured using the Inflammatory Bowel Disease Questionnaire (IBDQ): IBDQ response (≥16-point improvement from baseline in IBDQ total score) and IBDQ remission (IBDQ total score ≥ 170; higher scores indicating better disease specific QoL).4,5 BU was assessed using the Urgency Numeric Rating Scale (UNRS), an 11-point scale ranging from 0 (“no urgency”) to 10 (“worst possible urgency”), with both BU CMI (≥3-point change) and BU remission (UNRS score of 0 or 1), measured in patients with a baseline UNRS of ≥3.6 The association between BU improvement (CMI or remission) and IBDQ (response or remission) was evaluated using the chi-square test of association among patients with baseline UNRS ≥3 who achieved clinical response. This analysis was repeated among patients who achieved clinical remission.
Results
Among patients achieving clinical response, a significantly higher proportion achieved IBDQ response and IBDQ remission when they also achieved BU CMI or BU remission compared with those who did not both at W12 and W52 (p<0.005) (Table 1). Among patients who achieved clinical remission, achievement of BU CMI was significantly associated with IBDQ response (p<0.005) but not IBDQ remission, and achievement of BU remission was significantly associated with IBDQ remission (p<0.005) but not IBDQ response at W12; achieving BU remission was significantly associated with better IBDQ response and IBDQ remission at week 52 (p<0.05).
Table 1. Association of Clinical Remission and Response with achievement of Bowel Urgency Remission and CMI on IBDQ Response/Remission in patients with UC at W12 and W52 of Continuous Treatment
| IBDQ Response (W12), p-value* | IBDQ Remission (W12), p-value* | IBDQ Response (W52), p-value* | IBDQ Remission (W52), p-value* |
| Clinical Response + BU CMI | 368 (91.54%) |
| 291 (72.39%) |
| 261 (95.26%) |
| 233 (85.04%) |
|
| Clinical Response - BU CMI | 165 (71.74%) | <.0001 | 126 (54.78%) | <.0001 | 71 (83.53%) | 0.0003 | 59 (69.41%) | 0.0012 |
| Clinical Response + BU Remission | 178 (93.19%) |
| 169 (88.48%) |
| 174 (96.67%) |
| 166 (92.22%) |
|
| Clinical Response - BU Remission | 355 (80.50%) | <.0001 | 248 (56.24%) | <.0001 | 158 (88.27%) | 0.0026 | 126 (70.39%) | <.0001 |
| Clinical Remission + BU CMI | 157 (93.45%) |
| 134 (79.76%) |
| 171 (98.28%) |
| 157 (90.23%) |
|
| Clinical Remission - BU CMI | 49 (80.33%) | 0.0035 | 42 (68.85%) | 0.0836 | 37 (88.10%) | 0.0017 | 32 (76.19%) | 0.0135 |
| Clinical Remission + BU Remission | 83 (92.22%) |
| 84 (93.33%) |
| 125 (99.21%) |
| 119 (94.44%) |
|
| Clinical Remission -BU Remission | 123 (88.49%) | 0.3587 | 92 (66.19%) | <.0001 | 83 (92.22%) | 0.0074 | 70 (77.78%) | 0.0003 |
| Note: Data is represented as n (%). *Used the chi-square test of association. P-values less than 0.05 are bolded. |
Conclusion
Among patients with UC from miri phase 3 trials, the additional improvement of BU (CMI or remission) to the achievement of clinical response or remission was associated with greater QoL assessed by IBDQ response and remission.
References
- D’Haens, G., et al. "OP26 Efficacy and safety of mirikizumab as induction therapy in patients with moderately to severely active Ulcerative Colitis: Results from the Phase 3 LUCENT-1 study." Journal of Crohn's and Colitis 16. Supplement_1 (2022): i028-i029.
- Dubinsky, M. C., et al. "867e: Efficacy and safety of mirikizumab as maintenance therapy in patients with moderately to severely active ulcerative colitis: results from the phase 3 LUCENT-2 study." Gastroenterology 162.7 (2022): S-1393.
- Dubinsky, M.C., et al. “Clinical Effect of Mirikizumab Treatment on Bowel Urgency in Patients with Moderately to Severely Active Ulcerative Colitis and the Clinical Relevance of Bowel Urgency Improvement for Disease Remission.” Crohn’s & Colitis 360, Volume 5, Issue 1, January 2023, otac044.
- Irvine EJ. Quality of life of patients with ulcerative colitis: past, present, and future. Inflamm Bowel Dis. 2008;14: 554-565.
- Irvine EJ. Development and subsequent refinement of the inflammatory bowel disease questionnaire: a quality-of-life instrument for adult patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 1999;28: S23-S27.
- Dubinsky, M. C., et al. "P138 Psychometric validation and interpretation of a patient-reported outcomes instrument to assess bowel urgency among adults with moderate to severe Ulcerative Colitis." Journal of Crohn's and Colitis 16. Supplement_1 (2022): i220-i222.
Disclosure
David T. Rubin receives grants or contracts from Takeda, and discloses consultancy fees with Abbvie, Altrubio, Allergan, Inc., American College of Gastroenterology, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Ltd., Bristol-Myers Squibb, Celgene Corp/Syneos, Cornerstones Health, Inc. (non-profit), GalenPharma/Atlantica, Genentech/Roche, Gilead Sciences, GoDuRn, LLC, InDex Pharmaceuticals, Ironwood Pharmaceuticals, Iterative Scopes, Janssen Pharmaceuticals, Eli Lilly and Company, Materia Prima, Pfizer, Prometheus Biosciences, Reistone, Takeda and Techlab, Inc. Jianmin Wu, Simin K Baygani, Nathan Morris, Theresa Hunter Gibble are employees of Eli Lilly and Company. Stefan Schreiber receives consultancy and/or personal fees from AbbVie, Arena, BMS, Biogen, Celltrion, Celgene, Falk, Ferring, Fresenius, Galapagos/Gilead, HIKMA, IMAB, Janssen, Lilly, MSD, Mylan, Pfizer, Prometheus, Takeda, and Theravance.