Introduction
Mirikizumab (miri) is an anti-IL23p19 antibody that has shown efficacy in Crohn’s disease (CD). We have previously shown that miri improves health-related quality of life (HRQoL) by 12 weeks as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) in a Phase 2, multicenter, randomized, double-blind, placebo (PBO)-controlled study (NCT02891226) conducted in patients (pts) with moderately-to-severely active CD. This analysis assesses IBDQ scores through Week 104 (W104).
Aims & Methods
At baseline, pts (N=191) were randomized 2:1:1:2 allocation amongst 4 treatment arms (PBO, and 200, 600, 1000mg miri, respectively, administered intravenously (IV) every 4 weeks (Q4W) at Weeks 0, 4, and 8). Pts who received miri and achieved ≥1 point improvement at W12 in Simple Endoscopic Score for Crohn’s Disease (SES-CD) were re-randomized 1:1 into double-blind maintenance to either continue IV treatment assignment Q4W (combined arms of 200, 600, and 1000mg miri IV treatment; IV-C; N=41) or to 300mg miri subcutaneous (SC; N=46) Q4W up to W52. Subjects who had clinical benefit from the maintenance period received 300mg SC Q4W from W52 to W104. For analysis purposes, all IV and all SC arms were pooled. IBDQ score change from baseline (BL), IBDQ response (improvement ≥16 points), and IBDQ remission (score ≥170 points) were assessed up to W104 in pts who achieved endoscopic improvement at W12. IBDQ scores, domain scores (bowel symptoms, systemic symptoms, emotional function, social function), response, and remission were analyzed by descriptive statistics. For IBDQ response and remission, missing data were imputed as nonresponse (NRI).
Results
Out of the 127 pts randomized to miri for induction, 68.5% (87/127) achieved endoscopic improvement at W12 and were rerandomized into maintenance. Among the W12 miri induction endoscopic improvers, IBDQ response rates at W52 were 75.6% (31/41) and 80.4% (37/46) and IBDQ remission rates were 65.9% (27/41) and 67.4% (31/46) in the IV-C and SC groups, respectively. Of the W12 endoscopic improvers, 74 finished W52 in the maintenance and entered period 3 (W52-W104) where 68 went on to complete treatment through W104. At W104, the IBDQ response rates were 81.8% (27/33) and 78.0% (32/41) and IBDQ remission rates were 69.7% (23/33) and 56.1% (23/41) in the IV-C and SC groups, respectively. W52 and W104 IBDQ outcomes and domain scores are reported in Table 1.
Table 1. Week 52 and Week 104 Safety and Efficacy Results in Week 12 endoscopic improvers.
Table 1
| Week 12 Endoscopic Improverse |
| Week 52 | Week 104 | Week 52 | Week 104 |
Miri IV-C
N=41 | Miri IV-C
N=33 | Miri SC
N=46 | Miri SC
N=41 |
| Total IBDQ scorea, mean (SD) | 188.5 (26.6) | 187.4 (21.8) | 180.8 (25.4) | 173.7 (32.1) |
| IBDQ responseb, n (%) | 31 (75.6) | 27 (81.8) | 37 (80.4) | 32 (78.0) |
| IBDQ remissionc, n (%) | 27 (65.9) | 23 (69.7) | 31 (67.4) | 23 (56.1) |
| IBDQ score change from baseline a, d mean | 64.3 | 67.1 | 66.4 | 57.9 |
IBDQ Domain Scores a, mean (SD)
Bowel Symptoms
Systemic Symptoms
Emotional Function
Social Function |
58.6 (8.8)
27.7(5.4)
70.5 (11.1)
31.8 (3.9) |
58.8 (6.5)
26.8 (5.1)
70.0 (9.9)
31.8 (3.4) |
57.3 (8.0)
25.8 (5.4)
67.1 (11.0)
30.6 (4.2) |
54.3 (9.8)
24.7 (6.6)
65.0 (13.1)
29.7 (5.3) |
aMean and (SD) for scores and changes in scores do not utilize imputation and therefore are based on patients with observed data at the indicated timepoint (IV week 52 N=35; IV week 104 N=29; SC week 52 N=41; SC week 104 N=33); bIBDQ response: ≥16-point improvement in IBDQ score; cIBDQ remission: total IBDQ score ≥170; dchange from baseline; e Endoscopic improvement: ≥1 point improvement in SES-CD at Week 12.
Abbreviations: IBDQ = Inflammatory Bowel Disease Questionnaire; IV-C = Intravenous arms combined; SC = subcutaneous; SD = standard deviation |
Conclusion
Treatment with miri produced clinically meaningful improvement in HRQoL as measured by IBDQ at W52 and W104 in pts who achieved endoscopic improvement after miri induction with moderately-to-severely active CD.
Disclosure
Bruce E Sands: Received fees for consulting and speaking from Abivax, Bristol Myers Squibb, Janssen, Lilly Pfizer, and Takeda; for consulting from AbbVie; Adiso Therapeutics; Alimentiv; Amgen; Arena Pharmaceuticals; Artizan Biosciences; Artugen Therapeutics; AstraZeneca; Bacainn Therapeutics; Boehringer-Ingelheim; Boston Pharmaceuticals; Calibr; Celltrion Healthcare; ClostraBio; Cytoki Pharma; Connect Biopharma; Entera; Evommune; Fresenius Kabi; Galapagos; Genentech; Gilead Sciences; GlaxoSmithKline; Gossamer Bio; Imhotex; Immunic; Index Pharmaceuticals; Inotrem; Innovation Therapeutics; Ironwood Pharmaceuticals; Kaleido; Kallyope; MiroBio; Morphic Therapeutics; MRM Health; OSE Immunotherapeutics; Progenity; Prometheus Biosciences; Protagonist Therapeutics; Q32 Bio; Redhill Biopharma; Sun Pharma; Surrozen; Synlogic; Target RWE; Teva; Theravance Biopharma; TLL Pharmaceutical; USWM Enterprises; VielaBio: VTA Labs; and personal fees and stock options for consulting from Ventyx Biosciences.
Vipul Jairath: Consulting/advisory board fees: AbbVie, Alimentiv Inc, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, Second Genome, Sorriso pharmaceuticals, Takeda, Teva, Topivert, Ventyx, Vividion; speaker’s fees: Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi
Brian G Feagan: Consultant for AbbVie, AbolerIS, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport Inc, Arena Pharma, Avoro Capital Advisors, Atomwise,, BioJamp, Biora Therapeutics, Boehringer-Ingelheim, Boxer, Celsius Therapeutics,Celgene/BMS, Connect BioPharma, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium,, First Wave, First Word Group, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer Pharma, GSK, Hinge Bio, Hot Spot Therapeutics, Index Pharma, Imhotex, Immunic Therapeutics, JAKAcademy, Janssen, Japan Tobacco Inc., Kaleido Biosciences, Landos Biopharma, Leadiant, L.E.K. Consulting, Lenczner Slaght, LifeSci Capital, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics, Play to Know AG, Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen Inc., Takeda, Teva, Thelium, Tigenix, Tillotts, Ventyx Biosciences, VHSquared Ltd., Viatris, Ysios, Ysopia, Zealand Pharma. Speakers bureau for AbbVie, Janssen, Takeda. Member, Scientific Advisory Board, DSMB: AbbVie, Amgen, AMT, AnaptysBio, Boehringer-Ingelheim, Celgene/BMS Eli Lilly, Genentech/Roche, Janssen, MiroBio, Origo BioPharma, Pfizer, Prometheus, REDX Pharma, Sanofi, Takeda,Tillotts Pharma, Teva, Progenity, Index, Ecor1Capital, Morphic, GSK, Axio Research. Stock Shareholder: Gossamer Pharma. Other: Employee, Western University, Senior Scientific Director, Alimentiv Inc.
Alessandro Armuzzi: Consulting/advisory board fees: AbbVie, Allergan, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda; speaker’s fees: AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Tigenix; research grants: MSD, Takeda, Pfizer, Biogen
Peter Bossuyt: Received financial support for research from Abbvie, Amgen, Celltrion, Mylan, Pfizer and Takeda; lecture fees from AbbVie, Celltrion, Janssen, Lilly and Takeda; advisory board fees from Abbvie, Arena pharmaceuticals, BMS, Celltrion, Dr Falk, Galapagos, Janssen, Lilly, Pentax, PSI-CRO, Roche, Takeda and Tetrameros.
Theresa Hunter Gibble, Zhantao Lin, Kristina Traxler, Marijana Protic, and Rebecca Hozak: employees and shareholders of Eli Lilly and Company.
