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 (%) | Definition | 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.
