Introduction

The real-world GALOCEAN study showed that ~70% of patients have up to moderately active Ulcerative Colitis (UC).¹ A post hoc analysis of the SELECTION study (NCT02914522) found that patients with moderately active (MOD) UC were more likely to have sustained responses to filgotinib (FIL) than those with severely active (SEV) UC.²

Aims & Methods

We report outcomes for patients with MOD or SEV UC by Mayo endoscopic subscores (ES) in a post hoc analysis of SELECTION. In the phase 2b/3, double-blind, placebo-controlled SELECTION study, 659 patients (18–75 years old) with moderately to severely active UC were randomized (2:2:1) at week 0 (W0) to daily oral FIL 200 mg (FIL200) or 100 mg, or placebo (PBO) for 11 weeks in Induction Study A (biologic [bio]-naive) or B (bio-experienced [bio-exp]).³ FIL responders at week 10 (W10) were re-randomized (2:1) to FIL or PBO treatment until week 58 (W58). MOD or SEV UC subgroups were defined as a Mayo ES of 2 or 3, respectively. Proportions of patients achieving efficacy endpoints (Table) were compared between FIL200 and PBO for each subgroup.

Results

At W0, the mean Mayo Clinic Scores (SD) for MOD and SEV FIL200-treated bio-naive patients were 7.8 (1.1) and 9.2 (1.1); for bio-exp, 7.9 (1.3) and 9.6 (1.2). For MOD and SEV subgroups, 41% (46/112) and 66% (88/133) had CRP ≥3mg/L; 35% and 44% had a diagnosis of UC for ≥7 years. At W10 and W58, significantly greater achievement rates were observed for patients taking FIL200 vs PBO for most outcomes in both UC activity subgroups (Table). Numerical achievement rates at W10 were generally highest for FIL200-treated, bio-naive MOD patients (e.g. ES response: MOD, 46%; SEV, 24%). By W58, numerical differences between severity subgroups were less pronounced in bio-naive patients (e.g. ES response: MOD, 59%; SEV, 46%); differences between bio-exp subgroups were maintained.

Conclusion

These data show that patients with MOD or SEV UC treated with FIL200 have improvements in efficacy outcomes and quality of life vs PBO; at W10, patients with MOD UC were generally more likely to achieve a positive clinical outcome than those with SEV UC, especially in bio-naive patients. Numerical differences between subgroups for bio-naive patients became less pronounced over time because response rates increased in the SEV subgroup up to W58. Analyses of the response dynamics for patients with MOD and SEV UC (including other definitions of UC severity than ES) are ongoing.

Table. Outcomes for FIL200- or PBO-treated bio-naive patients at W10 and W58.

Outcomes, n/N (%)	Definitio​​​​n​​​​​​​​​​​​	Week 10 bio-naive MOD	Week 10 bio-naive SEV	Week 58 bio-naive MOD	Week 58 bio-naive SEV	Week 10 bio-exp MOD	Week 10 bio-exp SEV	Week 58 bio-exp MOD	Week 58 bio-exp SEV
Endoscopic remissionb	ES = 0	FIL200: 20/112 (17.9) PBO: 4/61 (6.6) p = 0.0337	FIL200: 10/133 (7.5) PBO: 1/76 (1.3) p = 0.0521	FIL200: 17/54 (31.5) PBO: 3/25 (12.0) p = 0.0793	FIL200: 9/55 (16.4) PBO: 2/29 (6.9) p = 0.2305	FIL200: 7/59 (11.9) PBO: 1/31 (3.2) p = 0.2587	FIL200: 2/203 (1.0) PBO: 2/111 (1.8) p = 0.2505	FIL200: 3/23 (13.0) PBO: 0/12 (0) p = 0.5271	FIL200: 2/70 (2.9) PBO: 1/33 (3.0) p = 0.3676
Endoscopic responseb	ES ≤ 1	FIL200: 51/112 (45.5) PBO: 18/61 (29.5) p = 0.0482	FIL200: 32/133 (24.1) PBO: 10/76 (13.2) p = 0.0581	FIL200: 32/54 (59.3) PBO: 6/25 (24.0) p = 0.0044	FIL200: 25/55 (45.5) PBO: 4/29 (13.8) p = 0.0072	FIL200: 24/59 (40.7) PBO: 8/31 (25.8) p = 0.1125	FIL200: 21/203 (10.3) PBO: 3/111 (2.7) p = 0.0067	FIL200: 10/23 (43.5) PBO: 1/12 (8.3) p = 0.1930	FIL200: 14/70 (20.0) PBO: 4/33 (12.1) p = 0.4743
MCS remissionb	ES ≤ 1, RB ≤ 1, SF ≤ 1, PGA ≤ 1, MCS ≤ 2	FIL200: 37/112 (33.0) PBO: 10/61 (16.4) p = 0.0292	FIL200: 23/133 (17.3) PBO: 7/76 (9.2) p = 0.1098	FIL200: 26/54 (48.1) PBO: 3/25 (12.0) p = 0.0019	FIL200: 23/55 (41.8) PBO: 4/29 (13.8) p = 0.0139	FIL200: 14/59 (23.7) PBO: 3/31 (9.7) p = 0.1429	FIL200: 11/203 (5.4) PBO: 3/111 (2.7) p = 0.1125	FIL200: 8/23 (34.8) PBO: 0/12 (0) p = 0.1255	FIL200: 12/70 (17.1) PBO: 2/33 (6.1) p = 0.1443
MCS responseb	RB ≤ 1 or reduction of ≥ 1, MCS reduction of ≥ 3 or 30%	FIL200: 79/112 (70.5) PBO: 30/61 (49.2) p = 0.0060	FIL200: 84/133 (63.2) PBO: 34/76 (44.7) p = 0.0103	FIL200: 40/54 (74.1) PBO: 11/25 (44.0) p = 0.0074	FIL200: 41/55 (74.5) PBO: 11/29 (37.9) p = 0.0013	FIL200: 36/59 (61.0) PBO: 8/31 (25.8) p = 0.0074	FIL200: 103/203 (50.7) PBO: 17/111 (15.3) p < 0.0001	FIL200: 14/23 (60.9) PBO: 2/12 (16.7) p = 0.0908	FIL200: 39/70 (55.7) PBO: 8/33 (24.2) p = 0.0339
Histologic remissionb	Categorical GS: grade 0 ≤ 0.3; grade 1 ≤ 1.1; grade 2A ≤ 2A.3; and grades 2B, 3, 4 and 5 = 0	FIL200: 44/112 (39.3) PBO: 13/61 (21.3) p = 0.0106	FIL200: 42/133 (31.6) PBO: 9/76 (11.8) p = 0.0015	FIL200: 28/54 (51.9) PBO: 5/25 (20.0) p = 0.0078	FIL200: 21/55 (38.2) PBO: 5/29 (17.2) p = 0.0782	FIL200: 19/59 (32.2) PBO: 3/31 (9.7) p = 0.0150	FIL200: 33/203 (16.3) PBO: 9/111 (8.1) p = 0.0808	FIL200: 9/23 (39.1) PBO: 1/12 (8.3) p = 0.2884	FIL200: 18/70 (25.7) vs PBO: 2/33 (6.1) p = 0.0095
pMCS remissionc	RB ≤ 1, SF ≤ 1, PGA ≤ 1 and pMCS ≤ 2	FIL200: 67/112 (59.8) PBO: 22/61 (36.1) p = 0.0027	FIL200: 65/133 (48.9) PBO: 21/76 (27.6) p = 0.0028	FIL200: 37/54 (68.5) PBO: 10/25 (40.0) p = 0.0119	FIL200: 39/55 (70.9) PBO: 9/29 (31.0) p = 0.0007	FIL200: 29/59 (49.2) PBO: 5/31 (16.1) p = 0.0120	FIL200: 58/203 (28.6) PBO: 7/111 (6.3) p < 0.0001	FIL200: 15/23 (65.2) PBO: 2/12 (16.7) p = 0.0499	FIL200: 33/70 (47.1) PBO: 5/33 (15.2) p = 0.0087
PRO-2 remissionc	RB = 0 and SF ≤ 1	FIL200: 71/112 (63.4) PBO: 23/61 (37.7) p = 0.0015	FIL200: 75/133 (56.4) PBO: 26/76 (34.2) p = 0.0020	FIL200: 35/54 (64.8) PBO: 11/25 (44.0) p = 0.0593	FIL200: 39/55 (70.9) PBO: 9/29 (31.0) p = 0.0006	FIL200: 34/59 (57.6) PBO: 4/31 (12.9) p = 0.0013	FIL200: 72/203 (35.5) PBO: 14/111 (12.6) p < 0.0001	FIL200: 15/23 (65.2) PBO: 2/12 (16.7) p = 0.0499	FIL200: 33/70 (47.1) PBO: 5/33 (15.2) p = 0.0084
MCS remission (CS-free)c	ES ≤ 1, RB ≤ 1, SF ≤ 1, PGA ≤ 1, MCS ≤ 2 and CSF for ≥ 6 months	N/A	N/A	FIL200: 11/54 (20.4) PBO: 0/25 (0) p = 0.0039	FIL200: 7/55 (12.7) PBO: 1/29 (3.4) p = 0.2457	N/A	NA	FIL200: 5/23 (21.7) PBO: 0/12 (0) p = 0.3173	FIL200: 2/70 (2.9) PBO: 1/33 (3.0) p = 0.5408
IBDQ remissionc	Score ≥ 170	FIL200: 66/112 (58.9) PBO: 21/61 (34.4) p = 0.0025	FIL200: 71/133 (53.4) PBO: 28/76 (36.8) p = 0.0218	FIL200: 38/54 (70.4) PBO: 14/25 (56.0) p = 0.1920	FIL200: 45/55 (81.8) PBO: 17/29 (58.6) p = 0.0236	FIL200: 32/59 (54.2) PBO: 6/31 (19.4) p = 0.0135	FIL200: 84/203 (41.4) PBO: 20/111 (18.0) p = 0.0005	FIL200: 17/23 (73.9) PBO: 7/12 (58.3) p = 0.7319	FIL200: 44/70 (62.9) PBO: 17/33 (51.4) p = 0.5015

^ap values are reported for comparisons between FIL200 and PBO within each severity subgroup. ^bPrespecified or ^cpost hoc outcomes.
CSF, corticosteroid-free; ES, endoscopic score; GS, Geboes score; IBDQ, Inflammatory Bowel Disease Questionnaire; MCS, Mayo Clinic Score; PGA, Patient Global Assessment; pMCS, partial Mayo Clinic Score; PRO-2, two-item patient reported outcome; RB, rectal bleeding subscore; SF, stool frequency subscore; W10, week 10; W58, week 58.

References

1. Löwenberg M et al. United European Gastroenterol J 2024;12 Suppl 2:406–7.
2. Schreiber S et al. United European Gastroenterol J 2024; doi:10.1002/ueg2.12686.
3. Feagan BG et al. Lancet 2021;397:2372–84.

Disclosure

MA reports grants, speaker and/or consultancy fees from Abbvie, Amgen, Astra Zeneca, Biogen, Boehringer-Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Egle Therapeutics, Ferring, Galapagos, Genentech/Roche, IQVIA, Janssen, Lilly, Novartis, Owkin, Pfizer, Spyre Therapeutics, Takeda, and Tillots Pharma.
JB reports grants and/or personal fees from AbbVie, Bristol Myers Squibb, Celgene, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Janssen-Cilag, MSD, Novo Nordisk Foundation, Orion Pharma, Pfizer, Pharmacosmos, Samsung Bioepis, Takeda, and Tillotts Pharma.
BV reports research support from AbbVie, Biora Therapeutics, Landos Biopharma, Nxera Pharma (previously Sosei Heptares), Pfizer, and Takeda; speaker fees from AbbVie, Biogen, Bristol Myers Squibb, Celltrion, Chiesi, Dr Falk Pharma, Eli Lily, , Ferring Pharmaceuticals, Galapagos, Johnson & Johnson, MSD, Pfizer, R-Biopharm, Sandoz, Takeda, Tillotts Pharma, Truvion and Viatris; consultancy fees from AbbVie, Alfasigma, Alimentiv, Applied Strategic, AstraZeneca, Atheneum, BenevolentAI, Biora Therapeutics, Boxer Capital, Bristol Myers Squibb, Eli Lily, Galapagos, Guidepoint, Inotrem, Ipsos, Johnson & Johnson, Landos Biopharma, Merck, Mylan, Nxera Pharma (previously Sosei Heptares), Pfizer, Progenity, Sandoz, Sanofi, Santa Ana Bio, Sapphire Therapeutics, Takeda, Tillotts Pharma and Viatris; and stock options for Vagustim.
AD reports fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and endpoint committees from Abivax, AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, Dr Falk Foundation, Galapagos, Gilead, Janssen, and Pfizer; consultancy fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Dr Falk Foundation, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Sandoz, Stada, Takeda, Tillotts, and Vifor Pharma; payment from lectures including service on speakers bureaus from AbbVie, Biogen, CED Service GmbH, Celltrion, Falk Foundation, Ferring, Galapagos, Gilead, High5MD, Janssen, Materia Prima, MedToday, MSD, Pfizer, Streamed-Up, Takeda, Tillotts, and Vifor Pharma; payment for manuscript preparation from Falk Foundation, Takeda, Thieme, and UniMed Verlag.
GF reports advisory board consultancy fees from AbbVie, Alfasigma, Celltrion, Ferring Pharmaceuticals, Janssen Pharmaceuticals, Pfizer, Sandoz, STADA and Takeda.
YZ reports support for conference attendance, speaker fees, research support and consultancy fees from AbbVie, Adacyte, Alfasigma, Almirall, Amgen, Boehringer Ingelheim, Dr Falk Pharma, Eli Lilly, Faes Farma, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Janssen Pharmaceuticals, Johnson & Johnson, Kern Pharma, MSD, Otsuka Pharmaceutical, Pfizer, Sanofi, Shire, Takeda and Tillotts Pharma.
MS reports has received grants or contracts from AbbVie, CMIC CMO, Kissei Pharmaceutical, Mochida Pharmaceutical, PPD-SNBL and Zeria Pharmaceutical; and payment or fees for lectures, presentations, speaker bureaux, manuscript writing or educational events from AbbVie, EA Pharma, Gilead Sciences, Janssen Pharmaceuticals, Kissei Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical, Nobelpharma, Takeda and Viatris.
WS was a consultant funded by Galapagos NV (former study sponsor) and is now a consultant funded by Alfasigma S.p.A. (current study sponsor)..
CR and VV were employees of Galapagos NV (former study sponsor) and are now employees of Alfasigma S.p.A. (current study sponsor).
PI reports lecture fees from AbbVie, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Gilead Sciences, Janssen Pharmaceuticals, MSD, Pfizer, Sandoz, Sapphire Medical, Shire, Takeda, Tillotts Pharma and Warner Chilcott; grants from Celltrion, Galapagos, MSD, Pfizer and Takeda; and advisory fees from AbbVie, Apriso, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Genentech, Gilead Sciences, Hospira, Janssen Pharmaceuticals, MSD, Pfizer, Pharmacosmos, Prometheus, Roche, Sandoz, Samsung Bioepis, Takeda, TopiVert, VH2, Vifor Pharma and Warner Chilcott.
The SELECTION trial was sponsored by Gilead Sciences, Inc. (Foster City, CA, USA), and Galapagos NV (Mechelen, Belgium) was a collaborator. These analyses were funded by Alfasigma S.p.A. Medical writing support for the development of this abstract was provided by Annika Pecchia-Bekkum, PhD, of PharmaGenesis London, London, UK, and was funded by Alfasigma S.p.A.

Introduction

Crohn’s disease (CD) is a chronic condition characterized by a relapsing-remitting course, often requiring intestinal resection. Postoperative management primarily aims to maintain clinical remission. The advent of biologic therapies has undoubtedly improved disease prognosis following initial surgery. However, access to this therapeutic class remains limited in lower-middle income countries such as Tunisia, necessitating the use of alternative agents, notably azathioprine (AZA), which has been widely used for this indication, albeit with controversial results.

Aims & Methods

This study aimed to evaluate the effectiveness of AZA in maintaining remission after a first intestinal resection in patients with ileal or ileocolonic Crohn’s disease, and to identify factors associated with treatment failure.
​We conducted a retrospective, descriptive, and analytical study in the gastroenterology department of Sahloul University Hospital in Sousse (Tunisia) over a 4-year period (2020–2024). We included all patients with ileal or right ileocolonic CD who underwent intestinal resection and received AZA in the postoperative period.

Results

A total of 66 patients were included, with a mean age at diagnosis of 31.50 ± 12.24 years and a male-to-female ratio of 1.06. The median interval between diagnosis and surgery was 21.5 months. During follow-up, AZA failure occurred in 63.6% of patients (n=42), with a mean time from surgery to failure of 44.71 ± 37.74 months. In univariate analysis, ileocolonic disease location (p=0.042), the total number of flares (p=0.007), and the number of severe flares (p<0.001) prior to surgery were significantly associated with AZA failure. Failure rates were also significantly higher in patients who underwent emergency surgery (p=0.007). Inflammatory resection margins (p<0.001) and severe inflammatory activity (p=0.007) were also significantly associated with treatment failure. In multivariate analysis, three independent risk factors were identified: the number of severe flares before surgery (p=0.031), preoperative inflammatory syndrome (p=0.008), and histopathological evidence of disease at the resection margins (p=0.004).

Conclusion

Our findings suggest that thiopurines remain a valuable therapeutic option in the management of Crohn’s disease, particularly in our setting, where access to alternative therapies is limited and associated with high costs.

Introduction

Vedolizumab (VDZ) is approved for moderate-to-severe inflammatory bowel disease (IBD; ulcerative colitis [UC] & Crohn’s disease [CD]).^1,2 While the subcutaneous (SC) formulation of VDZ is effective as maintenance treatment (mTx) in patients (pts) responding to intravenous (IV) VDZ induction treatment (Tx),^1,3 real-world data on Tx patterns of pts switching mTx from VDZ IV to SC or initiating mTx VDZ SC after IV induction are limited.

Aims & Methods

This prospective, non-interventional, multicentre (NCT05384080) study (conducted under the umbrella VARIETY protocol) enrolled adults with UC or CD initiating/undergoing induction with VDZ IV or continuing VDZ IV mTx, with the option to switch to VDZ SC mTx. The primary endpoint was real-world Tx patterns with VDZ, including Tx persistence. Additional endpoints assessed pt characteristics, pt-reported outcomes, and safety (adverse events [AEs]). Data were descriptively analysed.

Results

Overall, 162 enrolled pts (August 2022–June 2023; UC, n=103; CD, n=59) were included in the interim analysis. At enrolment, 127 (78.4%) received VDZ mTx (UC, n=78; CD, n=49) and 35 (21.6%), VDZ induction (UC, n=25; CD, n=10). The mean (SD) age was 38.2 (12.3) yrs, and time since IBD diagnosis was 10.7 (11.1) yrs. Majority of pts were male (96 [59.3%]), currently employed (124 [76.5%]), had never smoked (109 [67.3%]), and reported previous biologic therapy (95 [58.6%]). Demographic and IBD Tx history data were consistent across cohorts. At baseline, in pts with UC, the mean (SD) partial Mayo score was 1.8 (2.7); in pts with CD, the mean (SD) Crohn’s Disease Activity Index (CDAI) score was 90.6 (70.1). During the 1-yr study period, 20.0% (n=7; UC, n=2; CD, n=5) of pts in the induction and 51.2% (n=65; UC, n=40; CD, n=25) in the mTx cohort switched to VDZ SC. At week (W) 52, Tx persistence was 40.0% (n=14; UC, n=11; CD, n=3) and 77.2% (n=98; UC, n=61; CD, n=37) in the induction and mTx cohorts, respectively, and highest overall in mTx pts who switched to VDZ SC (86.2%; n=56; Table). The most common reason for Tx discontinuation was investigator decision (64.7%; n=33). For VDZ IV and SC, the mean (SD) number of doses per pt was 10.5 (7.6) and 23.8 (15.0), respectively. The median time from VDZ Tx initiation to SC Tx was 383 days (induction: 98 days; mTx: 434 days). In the induction cohort, the mean (SD) Work Productivity & Activity Impairment (WPAI) scores improved from 32.7 (24.1) at baseline (n=21) to 21.5 (31.2) at W52 (n=11), and the Short IBD Questionnaire (SIBDQ) scores improved from 44.1 (10.0) at baseline (n=34) to 51.0 (12.9) at W52 (n=15). In the mTx cohort, WPAI and SIBDQ results remained consistent over time. Fifty-three AEs were reported, including 4 serious AEs (malignancy, IBD flare requiring hospitalization, abdominal abscess, and unconsciousness). One AE of special interest (hypersensitivity reaction) was considered VDZ-related.

Data are presented as n/N (%). aInduction cohort includes pts who started the study with VDZ induction Tx. bMaintenance cohort includes pts who started the study with VDZ maintenance Tx. IV-SC are pts who started with VDZ IV and switched to SC during the study. IV-SC-IV are pts who switched from IV to SC and then back to IV. SC only are pts who received only VDZ SC during maintenance (with IV induction). IV, intravenous; CD, Crohn’s disease; SC, subcutaneous; Tx, treatment; UC, ulcerative colitis; VDZ, vedolizumab; W, week.
Tx persistence at W52	Total	IV only	SC only	IV-SC	IV-SC-IV
Overall	112/162 (69.1%)	53/86 (61.6%)	13/18 (72.2%)	59/72 (81.9%)	2/3 (66.7%)
Induction cohorta	14/35 (40.0%)	11/28 (39.3%)	-	3/7 (42.9%)	-
Maintenance cohortb	98/127 (77.2%)	42/58 (72.4%)	13/18 (72.2%)	56/65 (86.2%)	2/3 (66.7%)
UC cohort	72/103 (69.9%)	36/58 (62.1%)	8/12 (66.7%)	36/42 (85.7%)	1/2 (50.0%)
CD cohort	40/59 (67.8%)	17/28 (60.7%)	5/6 (83.3%)	23/30 (76.7%)	0 (0.0%)

Conclusion

In this Polish real-world study, high Tx persistence was reported, especially in pts who switched to VDZ SC. No new safety signals were noted. Overall, the results were consistent with those from other VARIETY cohorts,⁴ although lower persistence was observed during induction. The small size of the induction cohort was a limitation of this study.

References

1. Sandborn WJ, et al. Gastroenterology. 2020;158:562–72.e12.
2. Loftus EV Jr, et al. Aliment Pharmacol Ther. 2020;52:1353–65.
3. Vermeire S, et al. J Crohns Colitis. 2022;16:27–38.
4. Novacek G, et al. J Crohns Colitis. 2024;18(suppl 1):i1506–7

Disclosure

Conflicts of interest: Agata Michalak received lectures fees and/or travel grants from AbbVie, Bayer, Biocodex and Takeda. Katarzyna Karłowicz received lecture fees, consultancy fees or travel educational grants from Bristol Myers Squibb, AbbVie, Polpharma, Takeda and Pfizer. Renata Talar-Wojnarowska received lecture fees and/or travel grants from AbbVie, Astellas, Ferring, Janssen and Takeda. Adam Fabisiak received fees and/or travel grants from Bristol Myers Squibb, Pro. Med. CS, Pfizer and Polpharma. Magdalena Achtenberg received lecture fees from Ferring. Piotr Eder received lecture fees and/or travel grants from Takeda, Ferring, Astellas, Pfizer and Janssen. Maria Kłopocka received payment for lectures from Janssen, Takeda, Ferring, Alfasigma and Pharmabest and travel/accommodation/meeting expenses from Ferring, Janssen, Takeda, Alfasigma and Pharmabest. Maciej Gonciarz received compensation and/or research/educational grants from Pfizer, Polfarma, Abbvie, BMS, Ewoppharma, Ferring, Astellas, Takeda, Jansen-Cilag, Celtrion, Johnson & Johnson, and Sanofi. Grażyna Rydzewska received speaker and consultant fees from AbbVie, AlfaSigma, AstraZeneca, Bayer, Biocodex, Bristol Myers Squibb, Ferring, Janssen, Lilly, Pro. Med. Pl., Recordati, Sanprobi, SOBI and Takeda and travel/accommodation meeting expenses from AbbVie, Ferring and Takeda. Eliza Majewska is a permanent employee of Takeda Pharma Sp. z o.o. Maria Kopertowska-Majchrzak, Tomasz Romańczyk, Halina Cichoż-Lach, Małgorzata Zwolińska-Wcisło, and Elżbieta Poniewierka declare no conflicts of interest.
Funding: The study was funded by Takeda Pharma Sp. z o.o.
Acknowledgements: Medical writing support was provided by Michelle Rebello, PhD, of Cactus Life Sciences (part of Cactus Communications) and funded by Takeda Pharma Sp. z o.o.

Introduction

Bowel urgency (BU) is a common, debilitating symptom among patients with ulcerative colitis (UC).¹ LUCENT-URGE is a Phase 3b, open-label, single-arm 28-week (W) study in adults with moderately-to-severely active UC and BU (Urgency Numeric Rating Scale [UNRS] ≥3) at baseline treated with mirikizumab (MIRI). Here, we report W28 results from LUCENT-URGE (NCT05767021).

Aims & Methods

Patients were treated with intravenous MIRI 300 mg at W0, 4 and 8, followed by 200 mg subcutaneous at W12, 16, 20, and 24. The primary objective was to assess improvement in UNRS at W12. Key secondary objectives included evaluating the improvement in UNRS at W28, the improvement in Stool Deferral Time (SDT) and Bowel Urgency Frequency (BUF) at W12 and W28, the proportion of participants achieving clinical remission and an UNRS score of ≤1 (BU remission) at W12 and W28, and the proportion of participants achieving clinical response and an improvement in UNRS score ≥3 (clinically meaningful improvement [CMI] of UNRS) at W12 and W28. UNRS and BUF was measured using a daily diary where patients recorded the number of times they experienced BU in the past 24 hours and was averaged over a 7-day period. SDT was reported in minutes (min), and the shortest weekly SDT was used. Baseline observation carried forward was used as the endpoint for the corresponding visit for all missing observations. Missing continuous data were treated as no change from baseline and binary endpoints were treated as nonresponse for participants that discontinue prior to the time point of interest.

Results

172 patients were enrolled from 8 countries. Baseline modified Mayo score (MMS; mean± standard deviation [SD]) was 6.8±1.3, and 64.0% patients had severe disease activity (MMS 7-9). Baseline mean duration of UC was 8.0 years, mean UNRS score was 6.9 and mean BUF was 6.9 times/day. Mean UNRS and BUF improved from baseline to W28 by 3.6 and 3.8, respectively. The proportion of patients with SDT defined as “≥15 min or no urgency” was 4.1% at baseline and improved to 29.7% at W28 (Table 1). At W12, 36 (20.9%) patients achieved clinical remission, 54 (31.4%) achieved endoscopic remission, and 92 (53.5%) achieved CMI of UNRS. At W28, 62 (36.1%) patients achieved clinical remission, 76 (44.2%) achieved endoscopic remission, and 100 (58.1%) achieved CMI of UNRS. 76 (44.2%) patients achieved both clinical response and CMI of UNRS at W12, and 86 (50.0%) patients at W28. At W12 and W28, 8 patients (4.7%) and 28 patients (16.3%) achieved both clinical remission and BU remission, respectively. The safety profile of MIRI observed in LUCENT-URGE was consistent with previous studies, with no death reported and similar frequency of treatment-emergent adverse events (TEAEs). Most common TEAEs were ulcerative colitis exacerbation (5.2%) and upper respiratory tract infection (5.2%).

Table 1. Change in Bowel Urgency Measures from Baseline at Week 12 and Week 28, BOCF

BU Measures		Baseline	Week 12	Week 28
UNRS (BU severity) scorea [range 0-10], mean (SD)		6.9 (1.6)	3.7 (2.6)	3.3 (2.9)
BU Frequencyb [times/day], mean (SD)		6.9 (3.7)	3.1 (3.0)	3.1 (3.5)
SDTc, n (%)	<1 minute	34 (19.8)	15 (8.7)	14 (8.1)
	≥1 to <2 minutes	59 (34.3)	37 (21.5)	31 (18.0)
	≥2 to <5 minutes	57 (33.1)	52 (30.2)	45 (26.2)
	≥5 to <15 minutes	15 (8.7)	41 (23.8)	31 (18.0)
	≥15 minutes or no urgency	7 (4.1)	27 (15.7)	51 (29.7)
BOCF=Baseline Observation Carried Forward; BU=Bowel Urgency; CFB=Change from Baseline; IV= Intravenous; MIRI=Mirikizumab; UNRS= Urgency Numeric Rating Scale; SC= Subcutaneous; SD=Standard Deviation; SDT= Stool Deferral Time. aSeverity for the urgency (sudden or immediate need) to have a bowel movement in the past 24 hours using an 11-point scale ranging from 0 (no urgency) to 10 (worst possible urgency). Mean Week 28 CFB for BU severity was -3.6 times/day. bHow many times did the patient experience bowel urgency in the past 24 hours. Mean Week 28 CFB for BUF was -3.8 times/day. cIn the past 24 hours, how many minutes on average could the patient wait from the time they felt the urge to have bowel movement before rushing to the toilet. The shortest weekly SDT is calculated by taking the shortest response (i.e. minimum value) available over the past 7 days, where no urgency is treated as the largest value.

Conclusion

MIRI showed an early and sustained improvement on BU severity, frequency and stool deferral time through W28 in LUCENT-URGE. MIRI consistently improved clinical outcomes in patients with moderately-to-severely active UC.

References

Dubinsky M, et al. Bowel Urgency in Ulcerative Colitis: Current Perspectives and Future Directions. AJG 2023; 118(11): 1940-53.

Disclosure

SD reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli lilly and company, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor; lecture fees from AbbVie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda.
AD reports fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and end point committees from Abivax, AbbVie, Bristol Myers Squibb, Dr Falk Foundation, Galapagos, Gilead, Janssen, and Pfizer; consultancy fees from AbbVie, Alfasigma, Amgen, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Dr Falk Foundation, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Sandoz, Stada, Takeda, Tillotts, and Vifor Pharma; payment from lectures including service on speakers bureaus from AbbVie, Alfasigma, Biogen, CED Service GmbH, Celltrion, Falk Foundation, Ferring, Galapagos, Gilead, High5MD, Janssen, Materia Prima, MedToday, MSD, Pfizer, Streamed-Up, Takeda, Tillotts, and Vifor Pharma; payment for manuscript preparation from Abbvie, Falk Foundation, J & J, Takeda, Thieme, and UniMed Verlag.
DL declares counselling, boards, and transport or fees from AbbVie, Amgen, Biogen, Celltrion, Ferring, Alphasigma, Janssen, Lilly, MSD, Pfizer, Prometheus, Roche, Sandoz and Takeda.
JKL has received consultancy and speaker fees from AbbVie, Abivax, Arena, AlfaSigma, Bristol Myers Squibb, Biohit, Celltrion, Eli Lilly and Company, Ferring, Galapagos, Janssen, MSD, Pfizer, Takeda and Tillotts and research grants from AbbVie, Galapagos and Takeda.
RK reports lecture fees from Aboca S.p.A. Società Agricola, Ferring, AbbVie, and Eli Lilly and Company.
JDL consulted or served on an advisory board or data monitoring committee for Amgen, Arena Pharmaceuticals, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Galapagos, Gilead, Janssen Pharmaceuticals, Merck, Pfizer, Protagonist Therapeutics, Sanofi. He has had research funding or in kind support from Nestle Health Science, Takeda, Janssen Pharmaceuticals, AbbVie and Eli lilly and company. He has had educational grants from Janssen. He has performed legal work on behalf of manufacturers of generic ranitidine and 3M. He owns stock in Dark Canyon Labs.
ZY has received research support from AbbVie, Axcella, Bristol Myers Squibb, CymaBay, Galectin, Intercept, Inventiva, Madrigal, NGM, Novo Nordisk, NST, Poxel, and Sagimet; has acted as a speaker for AbbVie, Intercept, and Bristol Myers Squibb; and as a consultant for Intercept and Madrigal.
EC reports advisory board and consultant for Pfizer, Takeda, and PRIME Education; speaker for AbbVie, Eli Lilly and Company, Janssen, and Takeda.
KA, WJE, TT, IR are employees and minor shareholders of Eli Lilly and Company.
DR reports grant support from Takeda and has served as a consultant for AbbVie, AltruBio, Arena Pharmaceuticals, Bristol Myers Squibb, Eli Lilly and Company, Genentech, Gilead Sciences, Iterative Scopes, Janssen, Pfizer, Prometheus Biosciences, Roche, Takeda, and Techlab.
MD reports consulting fees from AbbVie, Arena Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Genentech (Roche), Gilead Sciences, Janssen, Pfizer, Prometheus Biosciences, Roche, Takeda Pharmaceuticals, and UCB; contracted research from AbbVie and Janssen; stock interest in Trellus Health; and licensing fees from Takeda Pharmaceuticals.

Introduction

Resolution of pain, fatigue and other symptoms are key treatment goals for many patients (pts) with Crohn’s disease (CD);^1,2 however, time to symptomatic improvement in pts treated with vedolizumab (VDZ) has not been formally evaluated.

Aims & Methods

VOICE (NCT06249555) is a prospective, observational study in pts with CD aged ≥18 years initiating VDZ or anti-IL-23 antagonist treatment (tx) per product labelling as part of standard of care, with the main objective to explore the time course of response to VDZ as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) domain Short Form (SF) scores. Inclusion criteria include baseline PROMIS Pain Interference (PI)-SF T-score ≥55 (0.5 SD above general population). We enrolled pts via Takeda pt support program in Canada, with additional pts enrolled at US and Canada sites. Planned sample size is 300 pts (VDZ, 200; anti-IL-23 antagonist [reference group not for formal comparison], 100); planned follow-up is 52 weeks (wks), with PROMIS PI data reported weekly for the first 14 wks. The primary endpoint is time to the first meaningful clinical improvement in PROMIS PI-SF T-score, defined as ≥2-point decrease in PROMIS PI-SF T-score from baseline. We also collect data on improvement in 7 PROMIS domains with clinical improvement defined as 5-point (0.5 SD)³ change in T-score from baseline, Short Inflammatory Bowel Disease Questionnaire (SIBDQ; including SIBDQ improvement [≥9 point increase from baseline] and SIBDQ remission [score of ≥60]) and safety. Here, we report the results from pts with ≥1 VDZ dose and ≥1 post-baseline PI assessment included in the interim analysis (IA; prespecified to occur after 50 pts from VDZ group completed or discontinued before the wk 14 assessment to provide an early evaluation of tx response and safety).

Results

Overall, 64 pts with ≥1 VDZ dose and ≥1 post-baseline PROMIS PI assessment (mean±SD age, 43.1±17.0 years, 35.9% male, 92.2% White) were included in the IA. Disease duration (mean±SD) was 6.4±12.1 years; 84.4% of pts were anti-TNF-naïve. Data collection is ongoing for 57 pts (49 with and 8 without completed wk 14 PROMIS PI questionnaire); 7 pts discontinued from the study. The median time to achieve the first ≥2_-point decrease in PROMIS PI-SF T-score (in n=56 pts) was 12 days (95% CI, 6-13). Baseline PROMIS domain scores indicated notable impairment; by wk 14, improvements in mean PROMIS scores from baseline were observed in all 7 measured domains, with ≥5-point improvements in 4/7 domains (Table). At wk 14, 37.5% (24/64) and 7.8% (5/64) pts achieved SIBDQ improvement and remission, respectively. One pt had serious adverse events of appendicitis and diverticulitis, and another pt had a fatal event; none of these were related to VDZ tx.

Table. Summary of PROMIS domain T-scores

PROMIS domain T-score, mean±SD	Baseline (n=64)	Week 14 (n=49)	Change from baseline (n=49)
Pain Interference	61.7±5.2	55.0±10.2	–6.5±10.0
Fatigue	62.0±6.4	53.9±11.5	–8.4±10.6
Anxiety	60.2±7.4	54.7±10.2	–5.5±8.6
Depression	56.4±8.6	52.9±10.9	–3.9±8.6
Physical Function	42.0±6.2	45.3±9.0	3.5±7.8
Sleep Disturbance	56.3±6.9	54.5±9.9	–1.5±7.2
Ability to Participate in Social Roles and Activities	43.2±6.3	49.0±11.2	5.9±10.1
T-score of 50±10 reflects the mean±SD score of the general US population.3 Higher T-scores in PROMIS Pain Interference, Fatigue, Anxiety, Depression and Sleep Disturbance domains reflect greater impairment (poorer quality of life); higher T-scores in PROMIS Physical Function and Ability to Participate in Social Roles and Activities domains reflect less impairment (better quality of life).4

Conclusion

The IA results through wk 14 show an early improvement across multiple symptom domains and quality of life in pts with CD starting VDZ tx. Time to first ≥2-point decrease in PROMIS PI-SF T-score was short, with a benefit observed after 12 days from VDZ initiation. Study recruitment and data collection are ongoing.

References

1. Keefer L, et al. Gastroenterology. 2022;162(5):1439-1451.
2. Kitchen H, et al. Crohns Colitis 360. 2020;2(2):otaa033
3. Cella D, et al. Value Health. 2019;22(5):537-544.
4. Shaw BE, et al. Cancer. 2018;124(4):841-849.

Disclosure

This study was sponsored by Alimentiv, Inc.
V. Jairath reports consulting/advisory board fees from AbbVie, Alimentiv, Anaptyis Bio, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ensho, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, MRM Health, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, Second Genome, Sorriso, Spyre, Synedgen, Takeda, TD Securities, Teva, Topivert, Ventyx, Vividion; speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, Tillotts and Fresenius Kabi.
M. Long reports consulting fees from AbbVie, Alimentiv, Bristol Myers Squibb, Intercept, Janssen, Lilly, Pfizer, Prometheus, Roivant, Syneos Health and Takeda; and research support from Lilly, Pfizer and Takeda.
M.D. Kappelman reports being a consultant to Eli Lilly and Takeda.
G. Radulescu and N. Li are employees of Alimentiv.
J.J. Wu, I. Romo Bautista, A. Insogna and C. Agboton are employees of Takeda and hold stock and/or share options in Takeda.
N. Narula has received advisory board/consulting honoraria from Abbvie, Amgen, Eli Lilly and Company, Ferring, Fresinius Kabi, Innomar Strategies, Iterative Health, Janssen, Novartis, Organon, Pfizer, Sandoz and Takeda.

Introduction

Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease of the esophagus. Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, significantly improved histologic and endoscopic outcomes versus placebo in Parts A and B of the EoE KIDS study in pediatric (1–11 years) patients with EoE (NCT04394351).

Aims & Methods

The aim of this analysis was to assess safety and efficacy of long-term dupilumab in the Part C open-label extension (OLE). Patients completing Week (W)52 in Part B were eligible for Part C, where they received the weight-tiered, open-label dupilumab regimen later approved by the FDA (similar to the Part A and B higher-exposure regimen). Part C ended early with FDA approval of dupilumab for pediatric patients with EoE; efficacy data to the last prespecified assessment at W100 are reported.

Results

102 patients enrolled in Part A, 98 in Part B, and 61 in Part C. At W100, the proportions of patients achieving peak esophageal intraepithelial eosinophil counts of ≤6 and <15 eosinophils/high-power field (eos/hpf) were similar/improved vs those observed with higher-exposure dupilumab through W52 of Part B: 70.7% vs 62.9% and 92.7% vs 85.7%, respectively. Additionally, mean (standard deviation) changes from Part A baseline at W100 were similar to those with higher-exposure dupilumab through W52 of Part B in EoE-Histologic Scoring System grade and stage scores (-0.85 [0.39] vs -0.97 [0.39], and -0.85 [0.36] vs -0.89 [0.32], respectively) and EoE-Endoscopic Reference Score (-5.34 [2.54] vs -4.77 [3.08]). Overall, 53/61 (86.9%) patients reported mild or moderate adverse events (AEs) and 3/61 (4.9%) reported serious AEs (none deemed related to dupilumab). The most common treatment-related AE during Part C was injection site reaction.

Conclusion

Dupilumab had a consistent, acceptable safety profile and maintained histologic and endoscopic efficacy in pediatric patients with EoE to W100. Future analyses will evaluate symptoms.

Disclosure

Chehade M: Adare Pharma Solutions/Ellodi, Allakos, AstraZeneca, BMS, Nexstone Immunology, Phathom, Recludix Pharma, Regeneron Pharmaceuticals Inc., Sanofi, Shire/Takeda ‒ consultant; Adare Pharma Solutions/Ellodi, Allakos, AstraZeneca, Celgene/BMS, Danone, Regeneron Pharmaceuticals Inc., Shire/Takeda ‒ research funding. Dellon ES: Abbvie, Adare/Ellodi, Akesobio, Alfasigma, ALK, Allakos, Amgen, Apollo, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biocryst, Bryn, Calypso, Celgene/Receptos/BMS, Celldex, EsoCap, Eupraxia, Dr. Falk Pharma, Ferring, GI Reviewers, GSK, Holoclara, Invea, Knightpoint, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Sanofi, Shire/Takeda, Target RWE, Upstream Bio – consultant; Allakos, Aqilion, Holoclara, Invea – educational grant. Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Celldex, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, Sanofi, Shire/Takeda – research funding; Allakos, Aqilion, Holoclara, Invea – educational grant. Pesek RD: Regeneron Pharmaceuticals Inc. ‒ advisory board. Collins MH: Alimentiv, Allakos, Arena, AstraZeneca, BMS, Calypso, EsoCap, GSK, Regeneron Pharmaceuticals Inc., Shire – consultant. Ashok D: Alexion Pharma, LaunchitDTx, Mirum Pharma ‒ consulting fees. Sanofi ‒ speaker fees. Liu R, Xia C: Regeneron Pharmaceuticals Inc. – employees and shareholders. Louisias M: Sanofi – employees, may hold stock and/or stock options in the company.