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
- Feagan BG et al. Lancet 2021;397:2372–84.
- Feagan BG et al. J Crohns Colitis 2022;16(Suppl1):i456–7.
- Feagan BG et al. J Crohns Colitis 2023;17(Suppl1):i47–50.
- 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.
