Introduction
Filgotinib (FIL) is a once-daily, oral, Janus kinase 1 preferential inhibitor approved for the treatment of patients with ulcerative colitis (UC) in the UK, EU and Japan. In the phase 2b/3 SELECTION trial (NCT02914522),1 FIL 200 mg (FIL200) was well tolerated and effective in inducing and maintaining clinical remission vs placebo (PBO) in patients with UC.
Aims & Methods
This post hoc analysis of SELECTION data further evaluated the prolonged benefit of FIL treatment from week 10 (W10) until W58. In SELECTION, adults with moderately to severely active UC were randomized 2:2:1 to receive FIL200, FIL 100 mg (FIL100) or PBO once daily for 11 weeks in Induction (IND) Studies A and B (biologic-naïve and -experienced patients, respectively). Patients in clinical remission or with a Mayo Clinic Score (MCS) response at W10 (responders) were rerandomized 2:1 to continue their IND FIL dose in the 47-week Maintenance (MNT) Study. This post hoc analysis evaluated the hazard ratio (HR) for protocol-specified disease worsening (PSDW) in patients who continued FIL200 during MNT (FIL200→FIL200) vs those rerandomized from FIL200 to PBO (FIL200→PBO). The proportion of patients with a prolonged benefit at W58 was also evaluated across all FIL200 and FIL100 MNT arms. A prolonged benefit was defined as clinical remission or an MCS response at W58, among W10 responders. Among patients with prolonged benefit at W58, the proportion of those who had Inflammatory Bowel Disease Questionnaire (IBDQ)-remission at W58 was also assessed across all FIL200 and FIL100 MNT arms.
Results
Baseline characteristics were similar between MNT arms, although biologic-experienced status was more common in patients who did not have a prolonged benefit vs those who did. FIL200→FIL200 treatment (n=199) reduced the risk of PSDW by 74% vs FIL200→PBO (n=98) (HR [95% CI]: 0.26 [0.17–0.40]; p<0.0001). PSDW was the most common reason for discontinuation among patients without prolonged benefit, across all arms. In the FIL200→FIL200 arm, 66.8% of patients who were in clinical remission or had an MCS response at W10 had a prolonged benefit at W58 vs 32.7% in the FIL200→PBO arm. Among patients in clinical remission at W10, 79.3% in the FIL200→FIL200 arm had a prolonged benefit (62.1% clinical remission; 17.2% MCS response) vs 44.4% in the FIL200→PBO arm (13.9% clinical remission; 30.6% MCS response). In the FIL200→FIL200 arm, 82.0% of patients with prolonged benefit at W58 had IBDQ remission at W58 (Table).
Table. Proportion of patients with prolonged benefit at W58 and proportion of patients in IBDQ remission at W58 among those with prolonged benefit at W58.
| Patients with outcome, n/N (%) | Maintenance treatment arm |
| FIL200→FIL200 | FIL200→PBO | FIL100→FIL100 | FIL100→PBO |
Prolonged benefit at W58 among patients:
in clinical remission or MCS response at W10
in clinical remission at W10
with MCS response at W10 |
133/199 (66.8)
46/58 (79.3)
87/141 (61.7) |
32/98 (32.7)
16/36 (44.4)
16/62 (25.8) |
87/172 (50.6)
34/54 (63.0)
53/118 (44.9) |
35/89 (39.3)
10/24 (41.7)
25/65 (38.5) |
| IBDQ remission at W58 among patients with prolonged benefit at W58 | 109/133 (82.0) | 20/32 (62.5) | 66/87 (75.9) | 29/35 (82.9) |
A prolonged benefit was defined as clinical remission or an MCS response at W58 among patients in clinical remission or MCS response at week 10. Data were stratified by clinical remission/MCS response status, which were mutually exclusive outcomes; if a patient was identified as being in clinical remission, they were not considered to have an MCS response.
Clinical remission = Mayo endoscopic subscore of ≤1, rectal bleeding subscore of 0 and a reduction of ≥1 point in stool frequency subscore from induction baseline to achieve a subscore of ≤1.
IBDQ remission = total IBDQ score ≥170.
MCS response was defined as a reduction of ≥ 3 points and ≥ 30% from induction baseline in MCS, with an accompanying decrease in rectal bleeding subscore of ≥ 1 point or an absolute rectal bleeding subscore of 0 or 1.
FIL100, filgotinib 100 mg; FIL200, filgotinib 200 mg; IBDQ, Inflammatory Bowel Disease Questionnaire; MCS, Mayo Clinic Score; PBO, placebo; W10, week 10; W58, week 58. |
Conclusion
After a year of FIL200 treatment, two-thirds of patients who were in clinical remission or had an MCS response at W10, and ~80% who were in clinical remission at W10, had a prolonged benefit.
References
Feagan BG et al. Lancet 2021;397:2372–84.
Disclosure
DL has received 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.
AS has received grant support from AbbVie; and consulting or speaker fees from AbbVie, Dr. Falk Pharma, Galapagos, Janssen Pharmaceuticals, MSD, Pfizer, Takeda and Tillotts Pharma.
TK has served as a speaker, a consultant or an advisory board member for AbbVie, Activaid, Ajinomoto Bio-Pharma, Alfresa Pharma, Asahi Kasei Medical, Astellas Pharma, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eisai, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen Pharmaceuticals, JIMRO, JMDC, Kissei, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, Thermo Fisher Scientific and Zeria Pharmaceutical; and has received research funding from AbbVie, Alfresa Pharma, Asahi Kasei Medical, EA Pharma, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Sekisui Medical, Thermo Fisher Scientific and Zeria Pharmaceutical.
TM reports personal fees from AbbVie, EA Pharma, Mitsubishi Tanabe Pharma and Takeda; and grant support from Mitsubishi Tanabe Pharma and Nippon Kayaku.
AO, MF and AdH are employees and shareholders of Galapagos NV.
CJ is a contractor at Galapagos NV.
SV reports grants from AbbVie, Galapagos, J&J, Pfizer and Takeda; consulting and/or speaker fees from AbbVie, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia Biologics, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, CvasThera, Cytoki Pharma, Dr Falk Pharma, Ferring Pharmaceuticals, Galapagos, Genentech/Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance Biopharma, Tillotts Pharma and Zealand Pharma.
The SELECTION trial was sponsored by Gilead Sciences Inc. Galapagos NV was a collaborator for the SELECTION trial and funded this analysis.
Medical writing support for the development of this abstract was provided by Elvi Nimali, MBiochem, of PharmaGenesis London, London, UK, and was funded by Galapagos NV.
