Introduction

In the randomized controlled LADI trial, a subset of patients with Crohn’s disease (CD) maintained clinical remission following extension of the adalimumab dose interval (1). The aim of this study was to assess long-term clinical outcomes for trial participants.

Aims & Methods

The initial LADI trial included CD patients in biochemical and corticosteroid-free clinical remission (CFCR) on adalimumab 40 mg/2 weeks. The intervention group started on a 3-week interval and increased to 4 weeks at week 24, if in clinical and biochemical remission. Controls remained on adalimumab every 2 weeks. In the current long-term study, additional data up to 3 years was collected. The primary endpoint was the proportion of patients in CFCR (Harvey Bradshaw Index (HBI) ≤4 or remission per Physician Global Assessment) without complications at year 3, while maintaining the baseline allocated adalimumab interval. Patients at an adalimumab interval >2 weeks or who discontinued for stable remission were also included in the primary endpoint. Complications were defined as IBD-related surgery or hospitalization, and new-onset or required treatment of fistulizing or penetrating disease. Secondary endpoints included CFCR and/or complications after escalation from randomized dose or discontinuation of adalimumab for reasons other than remission.

Results

Data was extracted for 143/174 initially randomized subjects (intervention: 95; control: 48). The primary endpoint was achieved in 34 of 95 patients (35.8%) in the intervention group and in 41 of 48 patients (85.4%) in the control group (p < 0.001). In the intervention group, 39/95 (41%) patients were on a de-escalated adalimumab dose at year 3: 10 (26%) 4-weekly, 25 (64%) 3-weekly, 4 (10%) stopped for stable remission. 35 (90%) patients were in CFCR, and 37 (95%) had no complications. In the control group, 44/48 (92%) were on the randomized or de-escalated dose at year 3: 30 (68%) 2-weekly, 10 (23%) 3-weekly, and 4 (9%) stopped due to remission. 42 (95%) patients were in CFCR and 42 (95%) had no complications. In the intervention group, another 39/95 (41%) patients required re-escalation of adalimumab at year 3: 33 (85%) 2-weekly, 5 (13%) weekly, and 1 (3%) every 10-days. 35 (90%) were in CFCR and 11 (28%) patients developed complications. In the control group, 2 (4%) patients required re-escalation to a weekly interval, and were in CFCR without complications at year 3. Median time to re-escalation was 6 months (Q1-Q3: 5-7) for the intervention group, and 29 (Q1-Q3: 28-30) for the control group. At year 3, 17/95 (18%) intervention and 2/48 (4%) control patients had discontinued adalimumab. 11 (65%) intervention patients and one control (50%) were in CFCR, and 4 (24%) and no complications occurred, respectively. Median time to adalimumab discontinuation was 19 (Q1-Q3: 8-29) and 24 months (Q1-Q3: 21-27) for the intervention and control patients, respectively.

Table 1. Baseline characteristics

Demographics	Intervention group (n = 95)	Control group (n = 48)
Age, years	40.7 (32.2 – 49.3)	44.1 (31.0 – 53.6)
Female	47 (49.5)	22 (45.8)
Ileocolonic disease	56 (58.9)	22 (45.8)
Non-stricturing, non-penetrating disease	56 (58.9)	28 (58.3)
Disease duration, years	13.6 (7.1 – 20.6)	11.8 (5.5 – 21.7)
Time on adalimumab, years	4.9 (2.4 – 7.0)	3.4 (1.9 – 7.2)
Concomitant immunosuppressants	17 (17.9)	12 (25.0)

Conclusion

Over one-third of CD patients in stable remission were on a de-escalated adalimumab dose at year 3, while maintaining CFCR without complications. Another quarter required adalimumab re-escalation but regained CFCR at year 3, without developing complications.

References

1. van Linschoten RCA, Jansen FM, Pauwels RWM, Smits LJT, Atsma F, Kievit W, et al. Increased versus conventional adalimumab dose interval for patients with Crohn's disease in stable remission (LADI): a pragmatic, open-label, non-inferiority, randomised controlled trial. Lancet Gastroenterol Hepatol. 2023;8(4):343-55.

Introduction

In this 12-month maintenance period analysis of the FilgoColitis study, we report on clinical effectiveness and psychosocial outcomes in ulcerative colitis (UC) patients newly initiated on filgotinib (FIL) therapy in a real-world setting. In addition, this study attempts to define novel patient-based outcomes monitored by wearable devices.

Aims & Methods

FilgoColitis is a prospective, multicentre, non-interventional, 24-month observational study in patients with active UC and newly introduced FIL therapy. Disease activity (response: reduction of pMayo by >3 points from baseline to month 6 and a reduction of at least 30% or reaching remission at month 6; clinical remission (CR): pMayo ≤ 1 plus a bleeding subscore=0; steroid-free remission: CR and no systemic use of steroids or oral budesonide) and quality of life (QoL) (sIBDQ and EQ-5D) will be analysed. In a subset, physical activity will be analysed using two different wearable devices (Garmin® smartwatch and SensMotion® accelerometer) with complete wearable data available for the two days immediately following both baseline and month 12 (n=17).

Results

202 UC patients with a newly introduced filgotinib therapy were enrolled in the study. After excluding missing outcomes, six patients were excluded due to incomplete baseline data. Out of the participants with complete baseline data (n=196), 106 (54.1%) used at least one wearable device during the study. To validate the smartwatch, all steps measured in parallel by both the smartwatch and the conventional accelerometer system were compared halfway through the recruitment period and showed good agreement with a positive correlation of 0.88 (p<0.001). Of the 196 patients with UC at baseline, 59.7% were male, and the median time since diagnosis was 8.0 years. Before treatment with FIL, 84.2% of patients had received biologic or small molecule therapies, and 55.6% had used immunosuppressants. Treatment persistence of these 196 baseline FIL patients at month 12 was 59.7% (Kaplan-Meier analysis). Of these 140 patients with complete baseline and month 12 data were available for the 12-month effectiveness analyses. After 12 months of treatment with FIL, the rates of clinical remission and steroid-free remission were 44.3% and 41.4%, respectively (Table 1, mITT analyses with switchers as outcome failures). There was no significant difference in clinical remission between biologic-naïve and biologic-experienced patients (50.0% vs 43.4%). Looking at week-10 responders only, the remission rate at month 12 was 66.2%. QoL improved significantly, with median EQ-VAS scores increasing from 68 to 80 at month 12 (p<0.001), and sIBDQ scores improving from 41.0 to 56.0 (p<0.001). In patients who were in remission at month 12, the number of steps measured during the night was lower than in patients who were not in remission: 170 (75-272) vs 342 (94-620). This was consistent with patients' reports of nocturnal bowel movements (0% versus 33.4%).

Table 1. Effectiveness of filgotinib therapy in UC patients at month 12 (mITT)

Outcome at month 12	all		bio-naïve	bio-experienced	p
n	140		18	122
Clinical response, n (%)	83 (59.3)		11 (61.1)	72 (59.0)	0.99
Clinical remission, n (%)	62 (44.3)		9 (50.0)	53 (43.4)	0.79
Steroid-free remission, n (%)	58 (41.4)		9 (50.0)	49 (40.2)	0.64

Conclusion

In this real-world study, FIL demonstrated a clinical remission rate of 44.3% at month 12 in patients with active UC, demonstrating a further improvement compared to the induction phase (CR 29.2% at week 10). QoL was also significantly improved.

Disclosure

BB has received consulting fees from: AbbVie, MSD, Shire, Ferring, Hospira, Takeda, Movetis, Shield Therapeutics, Pfizer, Biogen, Janssen, Hexal, and Celgene, outside the submitted work. Financial support for lectures and teaching from: AbbVie, Ferring, MSD, Merckle, Falk, HLR, Shield Therapeutics, Pfizer, Celltrion, Takeda, Janssen, and Mundipharma, outside the submitted work. Grant and financial support for research from AbbVie and Ferring, outside the submitted work.
SPD does not have any relevant financial or non-financial interests to disclose.
TH does not have any relevant financial or non-financial interests to disclose.
WL does not have any relevant financial or non-financial interests to disclose.
MK has received personal fees from AbbVie, Ferring, BMS, Galapagos, Janssen, and Amgen, outside the submitted work.
RE has received personal fees from: Takeda, AbbVie, MSD, Biogen, Hexal, Amgen, Celltrion, and Viatris, outside the submitted work.
LZ does not have any relevant financial or non-financial interests to disclose.
AS does not have any relevant financial or non-financial interests to disclose.
PE has received personal fees from: AbbVie, BMS, Galapagos, Janssen, and Amgen, outside the submitted work.
JR does not have any relevant financial or non-financial interests to disclose.
SFS does not have any relevant financial or non-financial interests to disclose.
TW does not have any relevant financial or non-financial interests to disclose.
SS has received personal fees from AbbVie, Arena, BMS, Biogen, Celltrion, Celgene, IMAB, Gilead, HIMA, IMAB-Biopharma, MSD, Mylan, Pfizer, Fresenius, Janssen, Takeda, Theravance, Provention Bio, Protagonist, and Falk, outside the submitted work.

Introduction

Mirikizumab is an interleukin (IL)-23 inhibitor approved for the treatment of ulcerative colitis (UC); however, real-world data are limited.

Aims & Methods

The Dutch Initiative on Crohn and Colitis (ICC) Registry is a prospective multicentre study collecting real-world data on advanced therapeutic agents in inflammatory bowel disease (IBD). Patients included in the current study had a confirmed diagnosis of UC and received at least one intravenous induction dose of mirkizumab before the 28^th of February 2025. Patients who did not use at least two therapies with different mechanisms of action (i.e. difficult-to-treat UC) or with colectomy were excluded. The primary endpoint was clinical remission at week (W) 12, defined as Simple Clinical Colitis Activity Index (SCCAI) ≤ 2. Secondary outcomes at W12 included corticosteroid-free (CSF) clinical remission (i.e. clinical remission without the use of systemic corticosteroids on the day of the visit), biochemical remission (faecal calprotectin (FC) level ≤ 250μg/g) and endoscopic remission (Mayo endoscopic subscore = 0). In addition, drug survival and adverse events were assessed.

Results

In total, 22 patients were included; 13 (59.1%) were male. Most patients (n = 12; 54.5%) were diagnosed with pancolitis. Patients had a median disease duration of 9.5 years (IQR 18.0). Twelve patients (54.5%) had used at least four different advanced therapies; 19 (86.4%) patients have previously used ustekinumab (IL-12/23 inhibitor). At treatment initiation, all patients showed active disease, either clinically, biochemically or endoscopically. Median SCCAI was 7.0 (IQR 6); median FC was 1696.5μg/g (IQR 2079). As the study is still ongoing, data at W12 were available for 19 (86.4%) patients. Clinical data were available for 14 patients; 35.7% (5/14) of them were in clinical remission. These five patients were also in CSF clinical remission. Similar rates were observed between ustekinumab-experienced and ustekinumab-naïve patients, although the naïve subgroup was rather small (3/14). Biochemical data were available for 12 patients; median FC was 1434.5μg/g (IQR 824). Only one (8.3%) patient was in biochemical remission at W12; this patient was ustekinumab-naïve. Another patient, with only endoscopic data, was in endoscopic remission. Two patients discontinued mirikizumab before W12: one patient stopped mirikizumab after the intravenous injection because of fever; the other patient showed no response. Four other patients discontinued mirikizumab after W12; none of them were in clinical or biochemical remission at W12. Reasons for treatment discontinuation were primary non-response (5/6) and adverse event (1/6). Four adverse events were reported in four patients: nausea and skin problems, both classified as possibly related to the treatment, a gastrointestinal infection requiring antibiotics and fever during the infusion.

Conclusion

We found that 7/16 patients with difficult-to-treat UC were in either clinical, biochemical or endoscopic remission at W12. Moreover, all patients in clinical remission at W12 were not using other medications. Mirikizumab was well tolerated, although the follow-up period was relatively short. The ICC Registry is ongoing, and results with higher patient numbers with longer exposure to mirikizumab will be analysed to further characterise the real-world effectiveness and safety for patients with difficult-to-treat UC.

Disclosure

LMMV - none MRN - none ACdV - advisory boards for Takeda, Janssen, Bristol Myers Squibb, Abbvie, Pfizer, and Galapagos; research grants from Takeda, Janssen, and Pfizer WAvD - none MCV - speaker fees from Janssen-Cilag, Galapagos, and Ferring B.V. IM - advisory board/lecture fee from Abbvie, dr. Falk, and Janssen-Cilag FDMvS - adviser and/or speaker for Takeda, Galapagos, Dr. Falk, Lilly, and Janssen-Cilag; received an unrestricted grant from Takeda JMJ -consultant/speaker for AbbVie, Lilly, Takeda, and Janssen; consultant for MSD AGLB - none ML - consultancy/lecture fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen-Cilag, Johnson & Johnson, Medtronic, Pfizer, Takeda, and Tillotts Pharma; grants from Alfasigma, the Netherlands Federation of University Medical Centres, TKI, and ZonMW AEvdMDJ - speaker fee from AbbVie, Alfasigma, Ferring, Janssen Pharmaceuticals, Takeda, Tramedico, and Vedanta; grants from Norgine, Cablon, Alfasigma, and ZonMW MJP - speaker fee from BMS, Janssen Cilag, and Takeda; non-restricted research grants from Horizon 2020, ZONMW (Dutch national research fund), MLDS, Takeda, Johnson and Johnson, Abbvie, and Galapagos ZM - speaker fee from Friso – Friesland Campina, Galapagos, Eli Lilly, and Takeda (paid to host institution); advisory board fees from Johnson & Johnson, Eli Lilly, Pfizer (paid to host institution); grants from ZonMw, Niels Stensen Fellowship, MLDS, Top consortium for Knowledge and Innovation (TKI), and Galapagos MD - speaking fee from Bristol Meyers Squibb, Takeda, Galapagos, Janssen, and Dr. Falk; advisory board fees from Abbvie, Bristol Meyers Squibb, Celltrion, Galapagos/Alfasigma, Janssen, Takeda; grant/research support from Pfizer, Bristol Meyers Squibb, Galapagos Alfasigma, and Janssen

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

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

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.