Introduction

Ulcerative colitis (UC) is associated with debilitating symptoms that impair the quality of life (QoL) of patients; restoration of QoL is an important long-term treatment goal.¹ Upadacitinib (UPA), an oral, reversible Janus kinase inhibitor approved for the treatment of UC, improves health-related QoL (HRQoL) and patient-reported outcomes (PROs) with 1 year (yr) of maintenance therapy.^2-4 This post hoc analysis of the U-ACTIVATE long-term extension (LTE) study evaluated the long-term efficacy of UPA in sustaining PROs and HRQoL outcomes in patients who had received up to a total of 4 years (yrs) of UPA maintenance therapy.

Aims & Methods

This analysis included patients who completed 1 yr (52 weeks [wks]) in the U-ACHIEVE maintenance study and received UPA15 mg once-daily (QD) (UPA15) or UPA 30 mg QD (UPA30) maintenance treatment in the U-ACTIVATE LTE study. Patients receiving UPA15 or UPA30 who achieved clinical remission per Adapted Mayo score at maintenance wk 52 continued their double-blind treatment upon entering the LTE study. Nonremitters receiving UPA15 were escalated to UPA30, those receiving UPA30 continued UPA30, and those assigned to PBO were escalated to UPA15, all in a blinded manner. The UPA UC program was not designed to compare UPA15 and UPA30 doses. Efficacy was assessed at LTE wks 0, 96, and 144 (data cutoff date: 30 June 2024) and included the percentage of patients who achieved absence of abdominal pain, absence of bowel urgency, Inflammatory Bowel Disease Questionnaire (IBDQ) response, IBDQ remission, and a meaningful within-person change (MWPC) in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue; Short-Form Health Survey-36 version 2 Mental Component Score (SF-36v2 MCS), and SF-36v2 Physical Component Score (PCS). Data were reported using as-observed (AO) and modified nonresponder imputation (mNRI) methods (shown in Table). Safety was reported previously.²

Results

This analysis included 369 patients treated with UPA15 or UPA30 at wk 0 of LTE trial. In the AO analysis, patients treated with UPA15 or UPA30 achieved sustained improvements from LTE wk 0 to wk 144 in PROs and HRQoL assessments (Table), including the absence of abdominal pain, absence of bowel urgency, IBDQ response, IBDQ remission; and achieved MWPC in FACIT-Fatigue, SF-36v2 PCS, and SF-36v2 MCS. Similar results were observed for all endpoints with the more conservative mNRI analysis (Table).

Endpoint, (n/N) % [95% CI]a	AO analysisb		mNRI analysisc
	UPA 15 mg QD	UPA 30 mg QD	UPA 15 mg QD	UPA 30 mg QD
No abdominal paind Week 0 Week 96 Week 144	(94/142) 66.2 [58.4, 74.0] (84/109) 77.1 [69.2, 85.0] (61/83) 73.5 [64.0, 83.0]	(168/227) 74.0 [68.3, 79.7] (137/172) 79.7 [73.6, 85.7] (109/135) 80.7 [74.1, 87.4]	(94/142) 66.2 [58.4, 74.0] (101/142) 71.1 [63.4, 78.7] (99/142) 69.4 [61.6, 77.2]	(168/227) 74.0 [68.3, 79.7] (171/227) 75.5 [69.7, 81.3] (171/227) 75.5 [69.7, 81.3]
No bowel urgencyd Week 0 Week 96 Week 144	(107/142) 75.4 [68.3, 82.4] (97/109) 89.0 [83.1, 94.9] (76/83) 91.6 [85.6, 97.5]	(180/227) 79.3 [74.0, 84.6] (154/173) 89.0 [84.4, 93.7] (117/135) 86.7 [80.9, 92.4]	(107/142) 75.4 [68.3, 82.4] (116/142) 81.5 [75.0, 88.1] (114/142) 80.0 [73.2, 86.8]	(180/227) 79.3 [74.0, 84.6] (192/227) 84.7 [79.9, 89.5] (188/227) 82.7 [77.6, 87.8]
IBDQ responsee Week 0 Week 96 Week 144	(128/142) 90.1 [85.2, 95.0] (95/106) 89.6 [83.8, 95.4] (73/78) 93.6 [88.2, 99.0]	(203/221) 91.9 [88.2, 95.5] (156/171) 91.2 [87.0, 95.5] (117/129) 90.7 [85.7, 95.7]	(128/142) 90.1 [85.2, 95.0] (119/142) 84.1 [77.9, 90.3] (120/142) 84.2 [77.9, 90.5]	(203/227) 89.4 [85.4, 93.4] (196/227) 86.3 [81.7, 90.9] (193/227) 84.9 [80.0, 89.9]
IBDQ remissionf Week 0 Week 96 Week 144	(114/142) 80.3 [73.7, 86.8] (93/106) 87.7 [81.5, 94.0] (70/78) 89.7 [83.0, 96.5]	(188/227) 82.8 [77.9, 87.7] (156/174) 89.7 [85.1, 94.2] (116/132) 87.9 [82.3, 93.4]	(114/142) 80.3 [73.7, 86.8] (111/142) 78.0 [70.7, 85.3] (104/142) 73.2 [65.2, 81.3]	(188/227) 82.8 [77.9, 87.7] (189/227) 83.1 [77.5, 88.7] (180/227) 79.2 [73.2, 85.3]
MWPC in FACIT-Fatigueg Week 0 Week 96 Week 144	(95/142) 66.9 [59.2, 74.6] (65/111) 58.6 [49.4, 67.7] (51/84) 60.7 [50.3, 71.2]	(159/220) 72.3 [66.4, 78.2] (122/178) 68.5 [61.7, 75.4] (100/140) 71.4 [63.9, 78.9]	(95/142) 66.9 [59.2, 74.6] (82/142) 57.9 [49.1, 66.6] (83/142) 58.4 [49.4, 67.4]	(159/227) 70.0 [64.1, 76.0] (144/227) 63.4 [56.7, 70.0] (149/227) 65.8 [59.1, 72.5]
MWPC in SF-36v2 PCSh Week 0 Week 96 Week 144 MWPC in SF-36v2 MCSh Week 0 Week 96 Week 144 ​	(105/142) 73.9 [66.7, 81.2] (79/106) 74.5 [66.2, 82.8] (61/77) 79.2 [70.2, 88.3] (83/142) 58.5 [50.3, 66.6] (65/106) 61.3 [52.0, 70.6] (48/77) 62.3 [51.5, 73.2]	(173/220) 78.6 [73.2, 84.1] (134/171) 78.4 [72.2, 84.5] (103/126) 81.7 [75.0, 88.5] (147/220) 66.8 [60.6, 73.0] (116/171) 67.8 [60.8, 74.8] (84/126) 66.7 [58.4, 74.9]	(105/142) 73.9 [66.7, 81.2] (99/142) 70.0 [62.1, 78.0] (99/142) 69.9 [61.8, 77.9] (83/142) 58.5 [50.3, 66.6] (84/142) 59.2 [50.9, 67.6] (83/142) 58.5 [49.2, 67.7]	(173/227) 76.2 [70.7, 81.8] (164/227) 72.4 [66.1, 78.7] (166/227) 73.0 [66.6, 79.3] (147/227) 64.8 [58.5, 71.0] (146/227) 64.2 [57.5, 70.9] (142/227) 62.7 [55.6, 69.9]
Table. PROs and HRQoL Efficacy Analysis From the U-ACTIVATE Long-Term Extension Study. AO, as-observed; CI, confidence interval; FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy - Fatigue; IBDQ, inflammatory bowel disease questionnaire; MCS, mental component score; mNRI, modified nonresponder imputation; MWPC, meaningful within-person change; LTE, long-term extension; PCS, physical component score; QD, once-daily; SF-36v2, Short-Form Health Survey-36 version 2; UC, ulcerative colitis; UPA, upadacitinib; wk, week. Week 0 refers to LTE week 0 (week 52 of the maintenance study). Efficacy analysis includes patients who received UPA15 or UPA30 in cohort 2 of U-ACTIVATE LTE who were UPA 45 mg 8-wk induction responders and were enrolled from cohort 1 of the 52-week maintenance period of the U-ACHIEVE maintenance study. a95% CI for response rate is the synthetic result based on Student's t-distribution from PROC MIANALYZE procedure if there were missing data due to intercurrent events or is based on the normal approximation to the binomial distribution if there are no missing data due to intercurrent events. bAO analysis did not impute values for missing evaluations. AO will include all values collected in the study until the first dose change or enrolment into the dose optimization substudy. cmNRI considered patients as nonresponders on or after study drug dose escalation, or usage of UC-related rescue medication; missing data due to other reasons were imputed using multiple imputation. dQuantified as the percentage of patients who achieved the absence of symptom. eIncrease in IBDQ score ≥ 16 points from baseline of induction. fIBDQ total score ≥ 170. gIncrease in FACIT-F score ≥ 5 points from baseline of induction. hIncrease in SF-36v2 PCS/MCS ≥ 4.1 points from baseline of induction.

Conclusion

Patients with UC who responded to induction therapy and received long-term UPA maintenance therapy showed a sustained absence of symptoms and improvements in HRQoL, suggesting that UPA maintains long-term improvements in patient-reported outcomes.

References

1. Turner D, Ricciuto A, Lewis A, D’Amico F, Dhaliwal J, et al. Gastroenterology. 2021;160:1570–83.
2. Panaccione R, et al. J Crohn’s Colitis. 2025;19(S1):i84-i86 [abstract].
3. AbbVie Inc. RINVOQ (Upadacitinib) [package insert] U.S. Food and Drug Administration website. https://www.rxabbvie.com/pdf/rinvoq_pi.pdf. Revised May 2023. Accessed 25 Feb 2025.
4. AbbVie DG& CoK. RINVOQ. Summary of Product Characteristics. European Medicine Agency website. https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf. Revised Feb 2025. Accessed 25 Feb 2025.

Disclosure

Funding: AbbVie funded this study (U-ACTIVATE; NCT03006068) and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.

Acknowledgments: AbbVie and the authors thank the participants, study sites, and investigators who participated in this clinical trial. Paulette A. Krishack, PhD, of AbbVie, provided medical writing support; Angela T. Hadsell, BA, of AbbVie, provided editorial support.

Joana Torres has received grant funding/speaker fees from and/or has participated in advisory boards for AbbVie, Lilly, Takeda, Janssen, and Pfizer.

Corey A Siegel has served as a consultant, advisor, and/or speaker for CME activities and/or received grant funding from AbbVie, BMS, Celltrion, Fresenius, Janssen, Lilly, Napo, Pfizer, Prometheus, Prometheus Labs, Roivant, and Takeda.

Julian Panés received consultancy fees/honorarium from AbbVie, Alimentiv, Athos, Atomwise, Boehringer Ingelheim, Celsius, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Surrozen, Takeda, and Wasserman, and has served on a data safety monitoring board for Alimentiv, Mirum, Sorriso, Sanofi, and Surrozen.

Edward V. Loftus Jr. has served as a consultant for AbbVie, Abivax, Amgen, Astellas, Avalo, Biocon, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Fresenius Kabi, Genentech, Gilead, Iota Biosciences, Iterative Health, Janssen, Morphic Therapeutics, Ono Pharma, Takeda, and TR1X Bio; has received research grants from AbbVie, Genentech, Gilead, Janssen, Merck, and Takeda; and is a share owner of Exact Sciences and Moderna.

Remo Panaccione has received consulting fees, speaker fees, and research support from Abbott, AbbVie, Abbivax, Alimentiv Amgen, AnaptysBio, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen Pharmaceuticals, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Sanofi, Satisfai Health, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, Ventyx, and UCB.

Si Xuan, Nidhi Shukla, Ari Stromberg, Sina Ogholikhan, Leah Rizzo, and Dolly Sharma, are employees of AbbVie and may own stock options.

Gareth Parkesreports personal payments, honoraria, speaker fees, travel grants and/or fellowships from AbbVie, Allergan, Bristol Myers Squibb, Celltrion, Ferring, Galapagos, Janssen, Napp, Takeda, and Tillotts, and directorship and shareholding with Ampersand Health. TR reports personal grants from AbbVie; personal consulting fees from AbbVie, Arena, Aslan, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, MonteRosa, Mylan, MSD, Novartis, Numab, Pfizer, Roche, Sandoz, Takeda, UCB and XAP; membership of the ECCO Scientific Committee, and membership in the UEG Scientific Committee; director of Endoread.

Introduction

Guselkumab (GUS) intravenous (IV) induction followed by subcutaneous (SC) maintenance with 200mg q4w or 100mg q8w was effective in the GALAXI 2 & 3 phase 3 treat-through studies of participants (pts) with moderately to severely active Crohn’s disease (CD), with similar efficacy between both maintenance doses in the overall study populations. Here, we evaluated the efficacy of maintenance doses in subgroups by baseline disease activity and severity and inflammatory burden at Week (Wk) 12 to determine if some pts may receive additional benefit from the higher maintenance dose.

Aims & Methods

Eligible pts had moderately to severely active CD (CDAI 220–450 and mean daily stool frequency score >3 or abdominal pain score >1), SES-CD ≥6 (≥4 for isolated ileal disease), and inadequate response or intolerance to oral corticosteroids, AZA, 6-MP, MTX, or biologics. Pts were randomly assigned to GUS 200mg IV at Wks 0, 4, and 8, followed by GUS SC 100mg q8w (N=286) or 200mg q4w (N=296). The studies also included placebo and ustekinumab arms, but this analysis focused on differences between GUS maintenance doses. Wk48 endpoints included clinical remission (CDAI <150) and endoscopic response (≥50% improvement in SES-CD or SES-CD ≤2). Analyses of subgroups by baseline disease activity (CDAI >300 or SES-CD >12), and inflammatory burden (CRP >5) or endoscopic response at Wk 12 were prespecified but not multiplicity controlled.

Results

In the pooled GALAXI 2 & 3 dataset, pts with baseline high disease activity (CDAI >300 or SES-CD >12) had numerically greater clinical and endoscopic outcomes at Wk 48 with 200mg q4w compared with 100mg q8w. Pts with baseline CDAI >300 had numerically greater percentages of clinical remission (200mg: 68.0% [83/122] vs 100mg: 55.1% [65/118], respectively) and endoscopic response (52.5% [64/122] vs 44.1% [52/118]) at Wk 48. Pts with baseline SES-CD >12 also had numerically greater percentages of these outcomes (clinical remission: 77.0% [94/122] vs 65.1% [82/126] and endoscopic response 67.2% [82/122] vs 58.7% [74/126]). Pts with baseline CDAI ≤300 or SES-CD ≤12 had similar Wk 48 outcomes for both maintenance doses. Pts with greater inflammatory burden (CRP >5mg/L) at Wk 12 or who were not in endoscopic response at Wk 12 also had numerically greater clinical and endoscopic outcomes at Wk 48 with 200mg compared with 100mg (Table). Pts with CRP ≤5mg/L or who were in endoscopic response at Wk 12 had similar clinical and endoscopic outcomes for both maintenance doses. Results for individual GALAXI 2 & 3 studies generally trended in the same direction for all subgroups.

Table. Week 48 Outcomes by CRP and Endoscopic Response Status at Week 12
Week 48 outcome by status at Week 12	Guselkumab 200 mg q4w (N=278)	Guselkumab 100 mg q8w (N=268)
CRP>5mg/L at Week 12	107/278 (38.5%)	85/268 (31.7%)
Clinical remission at Week 48	76/107 (71.0%)	46/85 (54.1%)
Endoscopic response at Week 48	54/107 (50.5%)	31/85 (36.5%)
Not in endoscopic response at Week 12	177/278 (63.7%)	156/268 (58.2%)
Clinical remission at Week 48	120/177 (67.8%)	97/156 (62.2%)
Endoscopic response at Week 48	79/177 (44.6%)	50/156 (32.1%)
Clinical remission was defined as CDAI score <150; endoscopic response was defined as ≥50% improvement from baseline in SES-CD or SES-CD ≤2

Conclusion

Pts with high clinical or endoscopic disease severity at baseline, greater inflammatory burden after induction, or who had not achieved endoscopic response after induction showed greater clinical and endoscopic outcomes at Wk 48 with GUS 200mg SC q4w compared with 100mg SC q8w.

Disclosure

AA: AbbVie, Bristol Myers Squibb/Celgene, DiaSorin, Eli Lilly, Gilead, IBD Horizons, Johnson & Johnson, Pfizer, Takeda, and TLL Pharmaceuticals
TH: grants from AbbVie GK, Boston Scientific Corporation, EA Pharma Co. Ltd., JIMRO Co. Ltd., Kissei Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Pfizer Inc., Takeda Pharmaceutical Co. Ltd., and Zeria Pharmaceutical Co. Ltd.; consulting fees from AbbVie GK, Abivax, Bristol Myers Squibb, EA Pharma Co. Ltd., Gilead Sciences, Janssen Pharmaceutical K.K., Lilly, Mitsubishi Tanabe Pharma Corporation, and Pfizer Inc.; lecture fees from AbbVie GK, EA Pharma Co. Ltd., Janssen Pharmaceutical K.K., JIMRO Co., Kissei Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Co. Ltd.
DTR: consulting/speaker fees/advisory board for AbbVie, Altrubio, Apex, Avalo, Bristol Myers Squibb, Buhlmann Diagnostics, Celgene, Connect BioPharma, Intouch Group, Iterative Health, Johnson & Johnson, Lilly, Pfizer, Samsung Neurologica, and Takeda; Altrubio, Datos Health, and Iterative Health stock options; grants from Takeda; membership on Board of Directors of Cornerstones Health, Inc and Crohn’s & Colitis Foundation’s Board of Trustees.
NAT, RVR, JY, KYYW, and ZY: employees of and may own Johnson & Johnson stock.
WR: speaker for AbbVie, Celltrion, Ferring, Johnson & Johnson, Galapagos Medice, MSD, Roche, Pfizer, Sobi, Takeda; consultant for AbbVie, Amgen, AOP Orphan, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celltrion, Eli Lilly, Galapagos, Gilead, Index Pharma, Johnson & Johnson, Medahead, Microbiotica, Pfizer, Takeda; advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Galapagos, Johnson & Johnson, Pfizer; funding from AbbVie, Johnson & Johnson, Sandoz, Sanofi, Takeda.
BES: consulting fees from AbbVie, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, AstraZeneca, Biolojic Design, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Celltrion, Equillium, Enthera, Enveda Biosciences, Evommune, Ferring, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Imhotex, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Kaleido, Kallyope, Merck, Microba, Mirador Therapeutics, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Therapeutics, Reistone Biopharma, Sanofi, Sorriso Pharmaceuticals, Spyre Therapeutics, Sun Pharma, Surrozen, Target RWE, Teva, TLL Pharmaceutical, Tr1X, Union Therapeutics, Ventyx Biosciences, and Vividion Therapeutics; consulting /speaking fees from Abivax; consulting/speaking fees/other support from Lilly; research grants/consulting/speaking fees/other support from Bristol Myers Squibb, Johnson & Johnson, Pfizer, and Takeda; stock/options from Ventyx Biopharma.
SD: consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring, Gilead, Hospira, Inotrem, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity, Takeda, TiGenix, UCB, and Vifor; lecture fees from AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, and Takeda.
RP: consulting fees from Abbivax, Abbott, AbbVie, Alimentiv, Amgen, AnaptsyBio, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Johnson & Johnson, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Spyre Therapeutics, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Union Biopharma, Viatris, Ventyx, and UCB; speaker’s fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Johnson & Johnson, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda Pharmaceuticals; Advisory Boards for AbbVie, Alimentiv, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Johnson & Johnson, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, and Ventyx.

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

1. 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.