Introduction
Mirikizumab (MIRI), a p19-directed antibody against interleukin-23, demonstrated improvements in fatigue, abdominal pain (AP) and stool frequency (SF) at Week (W) 12 and W52 in the VIVID-1 clinical trial.1
Aims & Methods
The aim of this analysis is to show the effect of MIRI on fatigue, AP, SF and achievement of clinical remission by Patient-Reported Outcome (PRO; SF ≤3 and AP ≤1 and neither worse than baseline) in the VIVID-2 open-label extension study through W104. This analysis includes data from primary analysis set in patients with Crohn’s disease (CD) randomised to the MIRI treatment arm in VIVID-1 who achieved endoscopic response (≥50% reduction from baseline in Simple endoscopic score for CD) at W52 and continued the MIRI subcutaneous dosing (300 mg) in VIVID-2. Change from VIVID-1 baseline was measured for continuous endpoints. Endpoints included fatigue measured using FACIT-Fatigue (measured as change from baseline, and clinically-meaningful improvement of ≥6-points among patients with baseline ≤46), AP improvement (measured as change from baseline, and achievement of ≤1 among patients with baseline >1), SF improvement (measured as change from baseline, and achievement of ≤3 among patients with baseline >3) and clinical remission by PRO, assessed at W64 and 104. Missing data were handled using observed case (OC) and modified non-responder imputation (mNRI) for response rates, while using modified baseline observation carried forward (mBOCF) for change from baseline. Response rates were presented as unadjusted proportions with 2-sided 95% confidence intervals using the Rubin's Rules (mNRI). ANCOVA models were used for continuous variables, adjusting for baseline values and intervention group.
Results
Fatigue mean (standard error [SE]) change from baseline was 10.7 (0.56) at W64; 9.4 (0.59) at W104, (observed response, n [%]: 152 [67.6%] at W64; 136 [64.8%] at W104; Table). AP improved (mean [SE] change: −1.5 [0.04] at W64; −1.6 [0.05] at W104), with response rates increasing from 174 (77.3%) to 161 (84.7%). SF showed sustained improvement (mean [SE] change: −4.3 [0.14] at W64; −4.3 [0.16] at W104), with response rates reaching 155 (89.6%) at W104 (Table). Similar rates of achievement of clinical remission by PRO were observed (178 [73.6%] at W64; 165 [80.1%] at W104) (Table).
Table: Improvement in fatigue, abdominal pain, stool frequency and achievement of clinical remission by PRO up to Week 104
| | FACIT-Fatigue (N=251) | Abdominal pain (N=251) | Stool frequency (N=251) | Clinical remission by PRO (N=251) |
| Week 64 | Week 104 | Week 64 | Week 104 | Week 64 | Week 104 | Week 64 | Week 104 |
| Change from baselinea (mBOCF), LSM (SE) | 10.7
(0.56) | 9.4
(0.59) | −1.5
(0.04) | −1.6
(0.05) | −4.3
(0.14) | −4.3
(0.16) | NA | NA |
| Response (observed)b, n (%) (95% CI) | 152 (67.6)
(61.2–73.3) | 136 (64.8)
(58.1–70.9) | 174 (77.3)
(71.4–82.3) | 161 (84.7)
(78.9–89.2) | 175 (86.6)
(81.3–90.6) | 155 (89.6)
(84.2–93.3) | 178 (73.6)
(67.7–78.7) | 165 (80.1)
(74.1–85.0) |
Responseb (mNRI), %
(95% CI) | 67.1
(61.0–73.3) | 60.8
(54.4–67.2) | 76.7
(71.2–82.2) | 79.2
(73.7–84.7) | 85.8
(80.9–90.6) | 84.0
(78.8–89.2) | 72.6
(66.9–78.2) | 75.0
(69.4–80.7) |
CI, confidence interval; LSM, least squares mean; mBOCF, modified baseline observation carried forward; mNRI, modified non-responder imputation; n, no of patients; NA, not applicable; PRO, Patient-Reported Outcome; SE, standard error
aBaseline of VIVID-1 study
bFACIT-Fatigue: ≥6-point improvement for baseline score ≤46; Abdominal pain: achievement of ≤1 for baseline score >1; Stool frequency: achievement of ≤3 for baseline score >3; Clinical remission by PRO: SF ≤3 and AP ≤1 and neither worse than baseline
Conclusion
MIRI sustained improvement in fatigue, AP, SF and clinical remission by PRO through 104 weeks of continuous treatment. These consistent findings support the long-term treatment with MIRI to address key symptoms of CD.
References
- Ferrante, MarcTron, Emiliano, et al. The Lancet. 404 (10470):2423-2436.
Disclosure
PB: Received financial support for research from AbbVie, EG; lecture fees from AbbVie, AMC ICP, Amgen, Bristol Myers Squibb, Celltrion, Dr Falk Benelux, EG, Galapagos, Globalport, Lilly, Medtalks, Materia Prima, Pentax, Springer Media; served on an advisory board for AbbVie, Bristol Meyers Squibb, CIRC, Galapagos, Janssen, Lilly, Pentax, PSI-CRO, Roche, Takeda, Tetrameros. AA: Consultant for Geneoscopy; received research support from Takeda. AV, GY and JW: Employee and shareholder of Eli Lilly and Company. NL: Consultant for Eli Lilly and Company. JRA: Consultant for Janssen, Pfizer, Abbvie, Vedanta, Geneteche, Seres Therapeutics, Ferring, GSK, Merck, Bristol Myer Squibb, Roivant, Celltrion, and TRXBio, Xencor, Shattuck Labs; Speaker for Abbvie, Janssen. MC: Provided educational activities for AbbVie, China Medical System, IPSEN, Janssen, and Takeda; served on an advisory board for Boehringer Ingelheim and Janssen; and has support for clinical research from Janssen and Takeda.
