Introduction

The 52-week, phase 3 True North (TN) study (NCT02435992) demonstrated the efficacy and safety of ozanimod (OZA), a highly selective sphingosine 1-phosphate receptor 1 and 5 modulator, in patients (pts) with moderately to severely active ulcerative colitis (UC). A prior analysis reported the long-term safety of OZA up to ~4 y from TN baseline through Week (W) 142 of the ongoing TN open-label extension (OLE; NCT02531126).

Aims & Methods

This analysis assessed the cumulative long-term safety of OZA with an additional year of exposure (pt disposition available until OLE W190 [up to ~5 y of OZA]). All pts who entered the OLE from TN (ie, clinical nonresponders at W10 and those who lost response during maintenance or completed maintenance at W52) were included in this analysis. Treatment-emergent adverse events (TEAEs) were monitored from the first dose of OZA in TN or the OLE through data cutoff; exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY) are presented. Lab abnormalities, including absolute lymphocyte count (ALC) reductions, were assessed during the OLE through data cutoff.

Results

A total of 823 pts entered the TN OLE. At data cutoff, 43.0% of pts had completed OLE W190 and total OZA exposure was 2681 PY. Overall, the cumulative safety assessments did not meaningfully change with an additional year of OZA exposure (Table). EAIRs of TEAEs, serious TEAEs, and TEAEs leading to treatment discontinuation remained consistent, and there were no new cases of malignancy, bradycardia, third-degree atrioventricular (AV) block, myocardial ischemia, ischemic stroke, pulmonary embolism, deep vein thrombosis, or macular edema with an additional year of OZA exposure. Three pts newly developed infections; however, only 1 pt had a serious infection (keratouveitis), which was not related to treatment. Two additional pts experienced mild hypertension. Reductions in ALC <500 cells/µl were common in the OLE (57.2%), but few pts had ALC <200 cells/µl(6.6%). Occurrence of ALC <200 cells/µl was not temporally associated with serious or opportunistic infections. Most alanine aminotransferase and aspartate aminotransferase elevations were transient and resolved without treatment interruption, and no serious hepatic events occurred.

Table. Cumulative safety assessments during TN and the TN OLE in all pts who entered the OLE	Up to ~4 y of OZA exposurea (n=823) Total PYc = 2536 n (%) EAIRd		Up to ~5 y of OZA exposureb (n=823) Total PYc = 2681 n (%)e n (%)			Up to ~4 y of OZA exposurea (n=823) Total PYc = 2536 n (%) EAIRd		Up to ~5 y of OZA exposureb (n=823) Total PYc = 2681 n (%)e n (%)
TEAEs	685 (83.2)	85.5	687 (83.5)	85.1	Third-degree AV block	1 (0.1)	0.04	1 (0.1)	0.04
Serious TEAEs	158 (19.2)	7.0	163 (19.8)f	6.8	Hypertension	55 (6.7)	2.3	56 (6.8)	2.2
TEAEs leading to treatment discontinuation	64 (7.8)	2.5	66 (8.0)	2.5	Myocardial ischemia	3 (0.4)	0.12	3 (0.4)	0.11
Infection	378 (45.9)	22.7	381 (46.3)	22.1	Ischemic stroke	3 (0.4)	0.12	3 (0.4)	0.11
Herpes zoster	30 (3.6)	1.2	31 (3.8)	1.2	Pulmonary embolism	3 (0.4)	0.12	3 (0.4)	0.11
COVID-19	103 (12.5)	4.3	103 (12.5)	4.1	Deep vein thrombosis	3 (0.4)	0.12	3 (0.4)	0.11
Serious infection	44 (5.3)	1.8	45 (5.5)	1.7	Macular edema	3 (0.4)	0.12	3 (0.4)	0.11
Malignancy	18 (2.2)	0.71	17 (2.1)	0.63	Cystoid macular edema	3 (0.4)	0.12	3 (0.4)	0.11
Bradycardia	3 (0.4)	0.12	3 (0.4)	0.11

^aData cutoff of June 30, 2023. ^bData cutoff of January 10, 2024. ^cTotal PY was calculated as the sum of the number of years on study contributed by each pt from time of first dose to last date on study. ^dEAIRs were calculated as number of pts/PY × 100. ^eTN OLE is an ongoing study. Individual TEAE terms may not add up as harmonization of final data is pending. ^fFor the 5 pts who newly reported a serious TEAE, events included 1 pt each with UC exacerbation, colitis, pancreatitis, and umbilical hernia, and 1 pt with ulcerative keratitis and keratouveitis.

Conclusion

The ongoing safety profile of OZA is consistent with previous analyses, with no new safety concerns identified. Long-term OZA use representing 2681 PY of exposure continues to be well tolerated in pts with moderately to severely active UC.

Disclosure

Acknowledgment: This study was sponsored by Bristol Myers Squibb. Writing and editorial assistance was provided by Traci Stuve, MA, and Alexandra Stafford, PhD, of Peloton Advantage, LLC, an OPEN Health company, and was funded by Bristol Myers Squibb.

JT: received grants from AbbVie and Janssen; received advisory board or speaker fees from AbbVie, Bristol Myers Squibb, Janssen, Pfizer, and Sandoz.
RL: consulted for Bristol Myers Squibb and Pfizer.
KK: received lecture honoraria from Gore.
SL: consulted for AbbVie, Bristol Myers Squibb, Eli Lilly, and Janssen.
TK: served as an advisory board member, consultant, or speaker for AbbVie, Alfresa Pharma, Alimentiv, Astellas, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eli Lilly, Ferring, Galapagos, Gilead Sciences, Janssen, JIMRO, JMDC, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, ThermoFisher Scientific, and Zeria Pharmaceutical; received research funding from AbbVie, Alfresa Pharma, EA Pharma, Gilead, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Pfizer, Sekisui Medical, Takeda, ThermoFisher Scientific, and Zeria Pharmaceutical.
DB: served as advisory board member or consultant for AbbVie, Amgen, Arena, Atheneum, BNG Service GmbH, Bristol Myers Squibb, CED Service GmbH, Celltrion, DGVS, Diaplan, Doctorflix, Eli Lilly, Else Kröner-Fresenius-Stiftung, Falk Foundation, Ferring, Galapagos, Gastroenterology Today, GlaxoSmithKline, Guidepoint, Impulze, Janssen-Cilag, Medical Tribune, MedTrix, MSD, Mylan, Onkowissen, Pfizer, Pharmacosmos, Roche, Sandoz, Streamed Up, Takeda, Tetrameros, Thieme, Tillotts, UCB, Viatris, and Vifor Pharma.
LK: reported no conflicts of interest.
DM, NRS, AP, MD, HW, DW, MTO, and AJ: employees and/or shareholders of Bristol Myers Squibb.
BPA: consulted for AbbVie, Bristol Myers Squibb, Celltrion, Eli Lilly, Janssen, Medtronic, Pfizer, Prometheus, Samsung Bioepis, and Takeda; lectured for AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, and Takeda.

Introduction

Microscopic colitis (MC) refers to two pathologies – Collagenous colitis (CC) and Lymphocytic colitis (LC) that cause chronic watery diarrhoea, urgency, incontinence leading to significantly decreased quality of life¹. It is thought that MC develops due to a pathological immune response to intestinal luminal antigens in genetically predisposed individuals, with microbiota playing an important role^{2, 3}. However, the pathogenesis of MC is still unclear.

Aims & Methods

The aim of this study was to identify and characterize changes in bacterial composition of MC patients in terminal ileum and different colonic segments and determine its relation to the clinical course of disease. Biopsies from terminal ileum and six segments of the colon were collected during diagnostic colonoscopies. DNA extraction was performed using AllPrep DNA/RNA Micro Kit (Qiagen) following the manufacturer’s instructions. To determine bacterial composition, sequencing of the 16S rRNA variable region V3-V4 was conducted using the 27F and 338R polymerase chain reaction primers and sequenced on a MiSeq (2×250 bp; Illumina, Hayward, CA). Bioinformatic analysis was performed using DADA2, and taxonomic classification was carried out with the RDP classifier.

Results

Biopsy samples from 20 active CC patients, 20 active LC patients, and 50 controls demonstrated distinct microbial profiles across different intestinal segments, as revealed by beta-diversity and differential compositional analyses. Compared with controls, CC patients had consistent alterations in three bacterial families throughout the entire colon, with Erysipelatoclostridiaceae and Coriobacteriaceae decreased and Pasteurellaceae increased. Additionally, 35 families had segment-specific changes, and 25 families displayed altered abundance in the terminal ileum.
LC patients exhibited a consistent increase in Erisypelotrichaceae across the entire colon, with 38 other families showing segmental changes, and 12 families displaying altered abundance in the terminal ileum. Comparing LC and CC revealed a significantly different bacterial profile. LC showed lower abundance across many families, particularly in the right colon and terminal ileum. After sample collection, 15 CC patients and 12 LC patients received budesonide, with 3 CC and 2 LC patients having incomplete response. Beta diversity analysis revealed significant differences in the ascending colon and left side of the colon of CC patients based on response to budesonide. Patients with incomplete response to budesonide had an increased abundance of the genus Paucibacter. Similar tendencies were not observed in LC.
1 CC patient exhibited a quiescent disease course, 6 reached a sustained remission after treatment, 7 had a relapsing and 6 had a chronic active disease. Significant differences in beta diversity were observed in transverse, descending colon and rectum. Beta diversity of the descending colon had a medium correlation with disease behaviour. In the LC group 6 patients had a quiescent disease, 8 had a sustained remission after treatment, 3 exhibited a relapsing and 4 had a chronic active disease. No significant correlation between microbiota and disease behaviour was observed in LC.

Conclusion

This study showed significant differences in bacterial composition between CC, LC and controls in the terminal ileum and colon. In both CC and LC, bacterial alterations were not consistent throughout the entire colon but varied between different colonic segments. Microbiome differences based on response to budesonide and disease behaviour were observed in CC, but not LC.

References

1. Verhaegh BPM, Münch A, Guagnozzi D, et al. Course of Disease in Patients with Microscopic Colitis: A European Prospective Incident Cohort Study. J Crohns Colitis. 2021;15(7):1174-1183.
2. Miehlke S, Guagnozzi D, Zabana Y, et al. European guidelines on microscopic colitis: United European Gastroenterology (UEG) and European Microscopic Colitis Group (EMCG) statements and recommendations. United European Gastroenterol J. Published online 2020.
3. Burke KE, D’Amato M, Ng SC, Pardi DS, Ludvigsson JF, Khalili H. Microscopic colitis. Nat Rev Dis Primers. 2021;7(1).

Introduction

The role of the gut microbiota in inflammatory bowel disease (IBD) pathogenesis is widely acknowledged, with numerous bacteria identified as contributing factors. Little however is known about the part viruses play – a likely major component in the structuring and functioning of the gut microbiota. Understanding how viruses interact with the gut microbiota and host cells in the context of IBD could facilitate innovative treatment approaches and personalized interventions.

Aims & Methods

We explore the colonic and upper intestinal virome in patients with IBD compared with general population (GP) controls. Faecal (colonic) and effluent (upper intestinal) derived shotgun metaviromes of 100 IBD individuals (UC = 50, CD = 50) and 50 IBD individuals with an ileostomy, respectively were compared to faecal derived metaviromes of 50 GP individuals. Metaviromes were generated using a combination of shotgun methods and viral particle enrichment, allowing for identification of both eukaryotic and prokaryotic, dsDNA, ssDNA and RNA viruses. Viral diversity, composition and prevalence were compared by calculating Shannon diversity, Bray-Curtis distances and performing logistic regression analyses. P-values were adjusted using false discovery rate (FDR) to correct for multiple testing, where relevant; FDR<0.05 was considered significant.

Results

Similar to bacterial diversity in IBD versus GP samples, we see a significantly lower viral diversity in CD and UC colonic samples compared with the GP, and an even lower diversity when comparing upper intestinal samples to colonic samples (FDR<0.05). Comparing viral populations between groups, we observe that, whilst there is evident interindividual variability within groups, distinct clustering between colonic and upper intestinal samples can be seen, with colonic IBD samples clustering slightly more towards upper intestinal samples. When comparing viral group prevalences between GP and IBD colonic samples, 83 out of 260 viral groups present in IBD-UC samples are absent in the GP samples and 125 out of 302 viral groups present in the GP were absent in IBD-UC. For IBD-CD samples these numbers are 79 out of 248 and 133 out of 302, respectively. The top 3 viral groups that positively associated with IBD-UC samples are: one unknown phage group (predicted bacterial host: Parasutterella spp.), a group containing Lactobacillus phages (bacterial host: Lactobacillus spp.) and a group containing Lactococcus phages (bacterial host: primarily Lactococcus spp). The top 3 viral groups that positively associated with IBD-CD samples are: the same unknown phage group as for IBD-UC, and two other unknown phage groups (predicted bacterial hosts: primarily Enterocloster & Bacteroides spp, respectively).

Conclusion

This first comprehensive description of the gut virome across multiple gastrointestinal sites shows specific alterations in IBD. Many viral groups differentially present in the IBD intestine infect bacteria often associated with gut health and significantly reduced in IBD patients. Dysregulated bile acid signaling has also been implicated in the pathogenesis of IBD, with bacterial dysbiosis being linked to its cause. In IBD populations, we observe phages with the host E.bolteae – a bacteria increased in dysbiosis due to their potential to metabolise bile acids. We speculate that alterations in the gut virome composition are key events that disrupt the equilibrium between gut microbiota and host, promoting a pro-inflammatory state and driving IBD pathogenesis. The next steps will be to investigate the mechanisms underlying these complex interactions.

Disclosure

RKW unrestricted grants: Takeda, Johnson and Johnson, Tramedico, Ferring. Consultant: Takeda

Introduction

The Phase 3 QUASAR induction study evaluated efficacy and safety of guselkumab (GUS), an IL-23 p19 subunit antagonist, in patients (pts) with moderately to severely active UC with inadequate response, loss of response, or intolerance to corticosteroids, immunosuppressants, and/or advanced therapies (ie, tumor necrosis factor-alpha antagonists, integrin receptor antagonists, and/or Janus kinase inhibitors). Here we present results for effects of GUS induction on histologic and combined histologic and endoscopic outcomes at Week (Wk) 12.

Aims & Methods

Pts with a modified Mayo score of 5-9 and a centrally reviewed Mayo endoscopy subscore ≥2 at induction baseline were randomized 3:2 to receive either GUS 200mg IV or placebo (PBO) IV at Wks 0, 4, and 8. Colonic biopsies were collected during endoscopy at baseline and Wk12 to evaluate treatment effect on histology measured by using three methods: Geboes, Robarts Histopathology Index (RHI), and Nancy Histological Index (NHI). Histologic improvement (Geboes histologic score ≤3.1), histologic remission (Geboes histologic score ≤2 B.0), the combination of histologic improvement and endoscopic improvement (Geboes histologic score ≤3.1 and Mayo endoscopy subscore of 0 or 1 with no friability; histo-endoscopic mucosal improvement; HEMI), and the combination of histologic remission and endoscopic normalization (Geboes histologic score ≤2 B.0 and Mayo endoscopy subscore of 0) were evaluated at Wk12.

Results

Of the 701 pts randomized (mean age, 40.5yrs; female, 43.1%; mean UC disease duration, 7.52yrs; mean modified Mayo score, 6.9; Mayo endoscopy subscore of 3, 67.9%), 421 were treated with GUS, and 280 were treated with PBO. Baseline demographics and disease characteristics were similar across treatment groups. Histologic activity at baseline was similar across the GUS and PBO cohorts: mean Geboes total score (11.8 vs 11.9, respectively), mean RHI (16.6 vs 16.6), and mean NHI (2.7 vs 2.8). The proportion of pts with histologic improvement at Wk12 was 44.9% among GUS-treated pts and 21.4% among those treated with PBO (adjusted Δ: 23.7%; nominal p<0.001; Table). Histologic remission at Wk12 was achieved by 39.9% and 18.6% of pts receiving GUS and PBO, respectively (adjusted Δ: 21.5%; nominal p<0.001). Identical results were seen across two additional definitions of histologic remission (ie, RHI and NHI; Table). The proportion of GUS-treated pts who achieved HEMI at Wk12 was greater than PBO-treated pts and highly significant (23.5% vs 7.5%, respectively; adjusted Δ: 16.2%; p<0.001). Lastly, histologic remission and endoscopic normalization at Wk12 was achieved by a greater proportion in the GUS group than PBO group (13.5% vs 3.9%, respectively; adjusted Δ: 9.8%; nominal p<0.001).

Table. Summary of Histologic and Combined Histologic and Endoscopic Outcomes at Week 12
	Placebo IV	Guselkumab 200 mg IV	Adjusted treatment difference (95% CI) p-value
Full analysis set, N	280	421	-
Histologic improvement, n (%) (Neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system [ie, Geboes histologic score ≤3.1])	60 (21.4)	189 (44.9)	23.7 (17.0, 30.3) Nominal p<0.001
Histologic remission, n (%) (Absence of neutrophils from the mucosa [both lamina propria and epithelium], no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system [ie, Geboes histologic score ≤2 B.0])a	52 (18.6)	168 (39.9)	21.5 (15.1, 27.9) Nominal p<0.001
Histologic remission by alternative definition, n (%) (Nancy Histological Index ≤ 1)	52 (18.6)	168 (39.9)	21.5 (15.1, 27.9) Nominal p<0.001
Histo-endoscopic mucosal improvement, n (%) (Achieving a combination of histologic improvement [ie, Geboes histologic score ≤3.1] and endoscopic improvement [Mayo endoscopy subscore of 0 or 1 with no friability])	21 (7.5)	99 (23.5)	16.2 (11.1, 21.2) p<0.001
Histologic remission and endoscopic normalization, n (%) (Absence of neutrophils from the mucosa [both lamina propria and epithelium], no crypt destruction, and no erosions, ulcerations or granulation tissue according to the Geboes grading system [ie, Geboes histologic score ≤2 B.0] and Mayo endoscopy subscore of 0)	11 (3.9)	57 (13.5)	9.8 (5.8, 13.7) Nominal p<0.001
a This definition is equivalent to histologic remission by alternative definition using the Robarts Histopathology Index (RHI ≤ 3, with subscores of 0 for lamina propria neutrophils and neutrophils in the epithelium and without ulcers or erosion). Note: Patients who had a prohibited change in UC medication, an ostomy or colectomy, or discontinued study agent due to lack of therapeutic effect or due to an AE of worsening of UC, or due to other reasons except for COVID-19 related reasons (excluding COVID-19 infection) or regional crisis in Russia and Ukraine prior to Week 12 were considered not to have achieved the endpoint. Patients who had an unevaluable biopsy (i.e., a biopsy that was collected, but could not be assessed due to sample preparation or technical errors) or were missing the endoscopy subscore (if applicable) or any of the histology components pertaining to this endpoint (i.e., assessment of neutrophils in epithelium, crypt destruction, or erosions or ulcerations or granulations) at Week 12 were considered not to have achieved the endpoint. The adjusted treatment difference and confidence intervals were based on the Wald statistic with Cochran-Mantel-Haenszel weight. The p-values were based on the Cochran-Mantel-Haenszel (CMH) chi-square test, stratified by ADT-Failure status (Yes/No) and concomitant use of corticosteroids at baseline (Yes/No).

Conclusion

In this phase 3 induction study, pts with moderately to severely active UC treated with GUS 200mg IV induction experienced clinically meaningful improvements in histologic and combined histologic and endoscopic outcomes at Wk12.

Disclosure

Julián Panés reports consultancy fees/honorarium from Janssen; reports payment for lectures including service on speaker bureau from Janssen; and reports payment for development of educational presentations from Janssen.
Bruce E. Sands reports grants, consulting and speaking fees and other support from Janssen.
Laurent Peyrin-Biroulet reports personal fees from Janssen.
Shadi Yarandi, Kuan-Hsiang G. Huang, Matthew Germinaro, Sunandini Sridhar, Patrick Branigan, Ye Miao, and Hongyan Zhang are employees of Johnson & Johnson and own company stock/stock options.
Xavier Hébuterne reports clinical research funding from Janssen; serving on advisory boards for Janssen; and participating in lectures and educational activities for Janssen.
Tibor Gyokeres reports consulting fees from Janssen; lecture fees from Janssen; and support for attending meetings and/or travel from Janssen.
Fumihito Hirai served as a clinical investigator and consultant for Janssen.
Tadakazu Hisamatsu received consulting fees from Janssen Research & Development, LLC.
David T. Rubin has served as a consultant to Janssen Pharmaceuticals.
Brian G. Feaganreceived consulting fees from Janssen; a member of the speakers bureau for Janssen; support for attending meetings and/or travel from Janssen; participation on a Data Safety Monitoring Board or Advisory Board from Janssen.

Introduction

Filgotinib (FIL), a once-daily, oral, Janus kinase 1 preferential inhibitor, is approved for the treatment of ulcerative colitis (UC). FIL was effective in inducing and maintaining clinical remission and was well tolerated in the placebo-controlled phase 2b/3 SELECTION trial (NCT02914522).¹

Aims & Methods

The efficacy and safety of continued treatment with FIL 200 mg (FIL200) are being assessed in the long-term extension (LTE) study (SELECTIONLTE: NCT02914535). The study design of SELECTION has been published previously.¹ We now report the efficacy and safety of open-label FIL200 through up to 5 years of treatment: LTE week 192 in completers and LTE week 240 in induction non-responders. Completers were defined as patients who completed the SELECTION induction and maintenance studies, and non-responders were those without response at SELECTION week 10; all of whom entered the LTE study. A data cut-off of 23 March 2023 was used for this interim analysis. Proportions of patients who were in partial Mayo Clinic Score (pMCS) remission (pMCS ≤1) and Inflammatory Bowel Disease Questionnaire (IBDQ) remission (score ≥170) were reported both as observed cases and using non-responder imputation (NRI). Adverse events (AEs) and AEs of special interest (AESIs) were evaluated using exposure-adjusted incidence rates per 100 patient-years of exposure (PYE).

Results

This interim analysis included 148 completers and 372 non-responders. AEs and AESIs in patients treated with open-label FIL200 (2464.7 PYE) showed no new safety signals, and safety events were comparable to those seen in previous analyses. The proportions of patients who were in pMCS and IBDQ remission are shown in the Table. The proportions of patients who were in pMCS remission increased during SELECTION to reach 72.4% (FIL200, as observed) at week 58/LTE baseline and increased further during SELECTIONLTE (85.0% at LTE week 192) in completers. Proportions in pMCS remission increased more gradually over SELECTIONLTE, reaching 66.7% (FIL200–FIL200, as observed) at LTE week 240 in non-responders. Similar patterns were seen for IBDQ remission; 78.5% (FIL200, as observed) of completers were in IBDQ remission at week 58/LTE baseline, increasing to 84.8% by LTE week 192. In non-responders, increases in the proportions of patients who were in IBDQ remission were gradual, reaching 77.8% (FIL200–FIL200, as observed) at LTE week 240. NRI analyses showed similar but much more conservative results than the as observed analyses for both groups for both endpoints.

Conclusion

Filgotinib 200 mg was effective in maintaining symptomatic remission and health-related quality of life for up to 5 years. No new safety signals were identified, and rates of AEs under long-term exposure were comparable to those previously reported.^1–4 Prolonged treatment with filgotinib is efficacious for the long-term management of UC, and together with its proven safety profile, results in an acceptable benefit–risk profile.

Table. Proportions of patients in pMCS or IBDQ remission in SELECTION and SELECTIONLTE (observed case and NRI).

	Proportion of patients in pMCS remission % (n/N)			Proportion of patients in IBDQ remission % (n/N)
	Completers IND FIL200 → MNT FIL200 → LTE FIL200 (n = 148)	Non-responders IND FIL100 → LTE FIL200 (n = 212)	Non-responders IND FIL200 → LTE FIL200 (n = 160)	Completers IND FIL200 → MNT FIL200 → LTE FIL200 (n = 148)	Non-responders IND FIL100 → LTE FIL200 (n = 212)	Non-responders IND FIL200 → LTE FIL200 (n = 160)
Week 10 Observed NRI	45.6% (67/147) 45.3% (67/148)	– –	– –	68.0% (100/147) 67.6% (100/148)	– –	– –
Week 58/LTE baseline Observed NRI	72.4% (105/145) 70.9% (105/148)	0.5% (1/212) 0.5% (1/212)	1.3% (2/160) 1.3% (2/160)	78.5% (113/144) 76.4% (113/148)	16.0% (30/188) 14.2% (30/212)	26.8% (37/138) 23.1% (37/160)
LTE week 48 Observed NRI	75.4% (98/130) 66.2% (98/148)	41.9% (62/148) 29.2% (62/212)	44.4% (48/108) 30.0% (48/160)	82.0% (109/133) 73.6% (109/148)	63.3% (100/158) 47.2% (100/212)	61.9% (70/113) 43.8% (70/160)
LTE week 96 Observed NRI	83.3% (95/114) 64.2% (95/148)	58.2% (71/122) 33.5% (71/212)	64.0% (57/89) 35.6% (57/160)	81.5% (97/119) 66.0% (97/147)	71.2% (89/125) 42.0% (89/212)	66.3% (59/89) 36.9% (59/160)
LTE week 144 Observed NRI	81.1% (73/90) 51.0% (73/143)	58.3% (63/108) 29.7% (63/212)	63.3% (50/79) 31.3% (50/160)	82.5% (85/103) 60.3% (85/141)	78.1% (82/105) 38.7% (82/212)	70.9% (56/79) 35.0% (56/160)
LTE week 192 Observed NRI	85.0% (34/40) 46.6% (34/73)	66.7% (50/75) 24.8% (50/202)	65.4% (34/52) 22.4% (34/152)	84.8% (39/46) 44.8% (39/87)	77.3% (68/88) 33.5% (68/203)	76.7% (46/60) 30.5% (46/151)
LTE week 240 Observed NRI	– –	62.2% (23/37) 18.4% (23/125)	66.7% (14/21) 14.9% (14/94)	– –	79.5% (31/39) 21.1% (31/147)	77.8% (21/27) 19.3% (21/109)

References

1. Feagan BG et al. Lancet 2021;397:2372–84.
2. Feagan BG et al. J Crohns Colitis 2022;16(Suppl1):i456–7.
3. Feagan BG et al. J Crohns Colitis 2023;17(Suppl1):i47–50.
4. Feagan BG et al. UEG Journal 2023;11(Suppl 8).

Disclosure

The SELECTION trial was sponsored by Gilead Sciences, Inc. (Foster City, CA, USA), for which Galapagos NV (Mechelen, Belgium) was a collaborator. The SELECTIONLTE trial was sponsored by Galapagos NV (Mechelen, Belgium), who funded these analyses.

Medical writing support for the development of this abstract was provided by Katie Pillidge, PhD, of PharmaGenesis London, London, UK, and was funded by Alfasigma S.p.A.
The authors thank Alessandra Oortwijn for her contributions to this study.
AM and CR are employees of Alfasigma S.p.A at the time of abstract submission.
BGF reports grants and personal fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Janssen Biotech/Centocor, Johnson & Johnson/Janssen, Pfizer, Receptos and Takeda; and personal fees from Ablynx, ActoGeniX, AdMIRx, Akebia Therapeutics, Allergan, Atlantic Pharmaceuticals, Avaxia Biologics, Avir Pharma… Disclosures truncated – see poster for full details.
KM reports personal fees from AbbVie, Bristol Myers Squibb, Celltrion, EA Pharma, Eli Lilly, Gilead Sciences, Janssen Pharmaceuticals, JIMRO, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Pfizer, Takeda… Disclosures truncated – see poster for full details.
GR reports personal fees and/or speaker fees from AbbVie, AstraZeneca, Augurix Diagnostics, Boehringer Ingelheim, Bristol Myers Squibb, Calypso Biotech, Celgene, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, Fisher, Genentech, Gilead Sciences, Janssen Pharmaceuticals, MSD, Novartis, Pfizer, Phadia, Pierre Fabre, Roche, Takeda, Tillotts Pharma, UCB, Vifor Pharma… Disclosures truncated – see poster for full details.
DL reports consulting, advisory board and transport fees from AbbVie, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Janssen Pharmaceuticals, MSD, Novartis, Pfizer, Prometheus, Roche and Takeda.
SV reports financial support for research from AbbVie, Galapagos, Johnson & Johnson, Pfizer and Takeda; speaker and/or consultancy fees from AbbVie, Abivax, AbolerIS Pharma, AgomAb Therapeutics, Alimentiv, Arena Pharmaceuticals… Disclosures truncated – see poster for full details.
SD reports personal fees from AbbVie, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Enthera, Ferring Pharmaceuticals, Gilead Sciences, Hospira, Inotrem, Janssen Pharmaceuticals, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB and Vifor Pharma.
EVL has consulted for AbbVie, Alvotech, Amgen, Arena Pharmaceuticals, Astellas, Avalo Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Fresenius Kabi, Genentech, Gilead Sciences, Gossamer Bio, GSK, Iterative Health, Iota Biosciences, Janssen Pharmaceuticals, KSL Diagnostics… Disclosures truncated – see poster for full details.
IB reports personal fees from Galapagos, Gilead Sciences, Janssen Pharmaceuticals, Pfizer, Pharmacosmos, Takeda and Vifor Pharma.
SS reports personal fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos/Gilead Sciences, Hikma Pharmaceuticals, I-Mab, Janssen Pharmaceuticals, Morphic Therapeutic, MSD, Mylan, Pfizer, Protagonist Therapeutics, Provention Bio, Sandoz/Hexal, Takeda, Theravance Biopharma and Ventyx Biosciences
HJK has received consultancy fees from AbbVie, Johnson & Johnson, Celltrion and Takeda.
MF is an employee and shareholder of Galapagos NV.
AM is a former employee and shareholder of Galapagos NV, and an employee of Alfasigma S.p.A.
CR is a former employee and shareholder of Galapagos NV, and an employee of Alfasigma S.p.A.
LPB has received consulting fees from Abivax, AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celltrion, CONNECT Biopharma, Cytoki Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, Gossamer Bio, GSK, HAC Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen Pharmaceuticals, Medac, Mopac, Morphic, MSD, Norgine… Disclosures truncated – see poster for full details.