Introduction
Filgotinib (FIL) is a once-daily, oral, Janus 1 kinase preferential inhibitor approved for the treatment of ulcerative colitis (UC) in Europe and Japan. The efficacy and safety of FIL in patients with moderately to severely active UC was evaluated in the phase 2b/3 randomized, double-blind, placebo (PBO)-controlled SELECTION study (NCT02914522).1
Aims & Methods
This post hoc analysis aimed to identify characteristics of FIL-treated patients that were associated with achieving corticosteroid (CS)-free remission. Adults aged 18–75 years were randomized 2:2:1 to induction FIL 100 mg, FIL 200 mg or PBO once daily for 11 weeks in induction study A (biologic-naive) and B (biologic-experienced). At week 10, patients in clinical remission or with a Mayo Clinic Score (MCS) response were re-randomized 2:1 to continue their FIL regimen or PBO for 47 weeks in the maintenance study. This analysis included only data from patients receiving CSs at baseline. Using univariate logistic regression, we analysed characteristics associated with achieving clinical remission at week 58 without using CSs for UC over a continuous period of ≥6 months (CS-free remission). P values <0.05 were considered statistically significant.
Results
At baseline, 81, 37, 92 and 47 patients were receiving CSs in the maintenance FIL 100 mg (n=172), PBO-to-match (PTM) FIL 100 mg (n=89), FIL 200 mg (n=199) and PTM FIL 200 mg (n=98) groups, respectively. The rates of CS-free remission in the FIL 100 mg, PTM FIL 100 mg, FIL 200 mg and PTM FIL 200 mg groups were 13.6%, 5.4%, 27.2% and 6.4%, respectively. Age, body mass index, history of pancolitis, duration of UC, faecal calprotectin and C-reactive protein levels, MCS and concomitant use of systemic CSs, immunomodulators and aminosalicylates had no significant effect on CS-free remission in the FIL 200 mg group. Mean baseline Robarts Histopathology Index (RHI) (odds ratio [OR]=0.949, p=0.023) was significantly associated with 6-month CS-free remission in the FIL 200 mg group. A baseline Mayo endoscopic subscore (MES) of 2 (vs 3) was associated with significantly increased odds of 6-month CS-free remission in the FIL 200 mg and FIL 100 mg groups (Table). Being male, a former (vs current) smoker or biologic-experienced was associated with significantly reduced odds of 6-month CS-free remission in the FIL 200 mg group.
Table. Association between 6-month CS-free clinical remission (dependent variable) and baseline characteristicsa by treatment groups.
| Variable | FIL 200 mg (n=92)
ORb (95% CI) | PTM FIL 200 mg (n=47)
ORb (95% CI) | FIL 100 mg (n=81)
ORb (95% CI) | PTM FIL 100 mg (n=92)
ORb (95% CI) |
| Male (ref: female) | 0.325 (0.116, 0.916)
p=0.034 | 1.520 (0.128, 18.031)
p=0.740 | 0.702 (0.196, 2.515)
p=0.587 | 0.000 (0.000, NA)
p=0.996 |
Former smoker (ref: current)
| 0.078 (0.012, 0.508)
p=0.028 | NA (0.000, NA)
p=0.335 | 0.571 (0.047, 6.983)
p=0.906 | 1.000 (0.000, NA)
p=1.000 |
Baseline MES of 2 (ref: score of 3)
| 5.229 (1.953, 13.997)
p=0.001 | 0.875 (0.073, 10.425)
p=0.916 | 3.741 (1.013, 13.817)
p=0.048 | 0.000 (0.000, NA)
p=0.996 |
| Biologic-experienced (ref: biologic-naïve) | 0.231 (0.085, 0.632)
p=0.004 | 0.417 (0.035, 4.939)
p=0.488 | 0.334 (0.082, 1.366)
p=0.127 | 0.944 (0.055, 16.326)
p=0.969 |
aThe full list of baseline characteristics that were tested for association with 6-month CS-free remission is as follows: age, sex, body mass index, smoking status, history of pancolitis, duration of disease, faecal calprotectin and C-reactive protein levels, Robarts Histopathology Index, Mayo Clinic Score, Mayo endoscopic, rectal bleeding and stool frequency subscores, prior biologic treatment, prior tumour necrosis factor-α antagonist and vedolizumab treatment (in biologic-experienced patients), concomitant use of systemic CS, immunomodulators and aminosalicylates.
bOR = 0 or 1 or NA results from 0 counts due to small sample size.
CS, corticosteroid; FIL, filgotinib; OR, odds ratio; MES, Mayo endoscopic subscore; NA, not applicable; PTM, placebo-to-match; ref, reference. |
Conclusion
Most baseline characteristics analysed had no statistically significant effect on 6-month CS-free remission under FIL 200 mg treatment. Low baseline MES and RHI, female sex, being a current (vs former) smoker and biologic-naive may predict higher likelihood of sustained CS-free remission in patients receiving FIL 200 mg.
References
- Feagan BG et al. Lancet 2021;397:2372–84.
Disclosure
TK has served as an advisory board member, consultant or speaker for AbbVie, Activaid, Ajinomoto Bio-Pharma, Alfresa Pharma, Astellas Pharma, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eisai, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen Pharmaceuticals, JIMRO, JMDC, Kissei Pharmaceutical, 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, EA Pharma, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Sekisui Medical, Takeda, Thermo Fisher Scientific and Zeria Pharmaceutical.
AD reports fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and end point committees from Abivax, AbbVie, Arena Pharmaceuticals, Falk Foundation, Gilead/Galapagos, Janssen and Pfizer; consultancy fees from AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Boehringer Ingelheim, Bristol Myers Squibb/Celgene, Celltrion, Falk Foundation, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Janssen, MSD, Pfizer, Pharmacosmos, Roche/Genentech, Sandoz/Hexal, Takeda, Tillotts, and Vifor Pharma; payment from lectures, including service on speakers bureaus from AbbVie, Biogen, Celltrion, the Falk Foundation, Ferring Pharmaceuticals, Gilead/Galapagos, High5ImmunoTV, Janssen Pharmaceuticals, MSD, Pfizer, Takeda, Tillotts Pharma and Vifor Pharma; and payment for manuscript preparation from the Falk Foundation, Takeda, Thieme Medical Publishers and UNI-MED Verlag.
XR has served as an advisory board member, consultant or speaker for AbbVie, Amgen, Biogen, Celltrion, Ferring Pharmaceuticals, Galapagos NV, Janssen Pharmaceuticals, MSD, Pfizer, Sandoz and Takeda.
YF is an employee of Gilead Sciences K.K.
AO is an employee and shareholder of Galapagos NV.
CJ is a contractor for Galapagos NV.
TH has received lecture fees from Aspen Japan K.K., Janssen Pharmaceuticals, JIMRO, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical Co., Ltd., Pfizer and Takeda; research grants from AbbVie GK, Activaid, Alfresa Pharma Corporation, Bristol Myers Squibb, Eli Lilly Japan K.K., Ferring Pharmaceuticals, Gilead Sciences, Inc., Janssen Pharmaceutical K.K., JMDC Inc., Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Japan Inc. and Takeda; scholarship contributions from Mitsubishi Tanabe Pharma Corporation, Nippon Kayaku Co., Ltd. and Zeria Pharmaceutical Co., Ltd.; and study group sponsorship from AbbVie GK, EA Pharma Co., Ltd., JIMRO Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Otsuka Holdings and Zeria Pharmaceutical Co., Ltd.
This study was funded by Gilead Sciences K.K.
The SELECTION trial was sponsored by Gilead Sciences Inc (Foster City, CA, USA). Galapagos NV (Mechelen, Belgium) was a collaborator for the SELECTION trial.
Writing support for the development of this abstract was provided by Tamsyn Stanborough, PhD, and Georgii Filatov of Oxford PharmaGenesis, Melbourne, Australia, and funded by Gilead Sciences K.K.
