1Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
2Hokkaido Prefectural Welfare Federation of Agricultural Cooperatives, Sapporo-Kosei General Hospital, Sapporo, Japan
3Kyorin University School of Medicine, Tokyo, Japan
4Fukuoka University, Fukuoka, Japan
5Hyogo College of Medicine, Nishinomiya, Japan
6Toho University Sakura Medical Center, Sakura, Japan
7The Jikei University School of Medicine, Tokyo, Japan
8Alimentiv Inc., London, ON, Canada
9Western University, London, ON, Canada
10Galapagos NV, Mechelen, Belgium
11Galapagos NV, Leiden, Netherlands
12Gilead Sciences, Inc., Foster City, CA, USA
13Gilead Sciences K.K., Tokyo, Japan
14Tokyo Medical and Dental University, Tokyo, Japan
© Copyright 2023. Korean Association for the Study of Intestinal Diseases.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Funding Source
The SELECTION trial was sponsored by Gilead Sciences, Inc. (Foster City, CA, USA), and co-funded by Gilead Sciences, Inc. and Galapagos (Mechelen, Belgium).
Conflict of Interest
Hibi T has received lecture fees from Aspen Japan K.K., Janssen, JIMRO, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Pfizer, and Takeda Pharmaceutical; 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 Pharmaceutical Co., Ltd.; 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.
Motoya S has received lecture fees from Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, and Takeda Pharmaceutical Co., Ltd.; and research grants from AstraZeneca K.K., EA Pharma Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Pfizer Inc., and Takeda Pharmaceutical Co., Ltd.
Hisamatsu T has a joint research agreement with Alfresa Pharma Co., Ltd. and EA Pharma Co., Ltd.; and has received grant support from AbbVie GK, Daiichi Sankyo, EA Pharma Co., JIMRO Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Ltd., Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Inc., Takeda Pharmaceutical Co., Ltd., and Zeria Pharmaceutical Co., Ltd.; and consulting and lecture fees from AbbVie GK, Celgene K.K., Ltd., EA Pharma Co., Janssen Pharmaceutical K.K., JIMRO Co., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Co., Ltd.
Hirai F has received lecture fees from AbbVie GK, EA Pharma Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Co., Ltd.; research grants from Eli Lilly Japan K.K. and Janssen Pharmaceutical K.K.; scholarship contributions from AbbVie GK, Ayumi Pharmaceutical Corporation, EA Pharma Co., Ltd., Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., and Otsuka Pharmaceutical Co., Ltd.; and study group sponsorship from AbbVie GK, EA Pharma Co., Ltd., JIMRO Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, and Zeria Pharmaceutical Co., Ltd.
Watanabe K has received lecture fees from AbbVie GK, EA Pharma Co., Ltd., Kissei Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Pfizer Inc., and Takeda Pharmaceutical Co., Ltd.; research grants from EA Pharma Co., Ltd., EP-CRSU Co., Ltd., and Takeda Pharmaceutical Co., Ltd.; scholarship contributions from AbbVie GK, EA Pharma Co., Ltd., JIMRO Co., Mitsubishi Tanabe Pharma Corporation, and Nippon Kayaku Co., Ltd.; and study group sponsorship from AbbVie GK, Asahi Kasei Medical Co., Ltd., EA Pharma Co., Ltd., JIMRO Co., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Factory Inc., and Zeria Pharmaceutical Co., Ltd.
Matsuoka K has served as a scientific adviser for EA Pharma; has served on advisory boards for Boehringer Ingelheim, Bristol Myers Squibb, and Eli Lilly and Company; and has received personal fees from AbbVie, EA Pharma, Janssen, JIMRO, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Pfizer Inc, Takeda Pharmaceutical, and Zeria Pharmaceutical; and research grants from AbbVie, EA Pharma, JIMRO, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, and Takeda Pharmaceutical.
Saruta M has received consulting and lecture fees from EA Pharma Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Ltd., and Takeda Pharmaceutical Co., Ltd.; and research grants from EA Pharma Co., Ltd., EP-CRSU Co., Ltd., Mitsubishi Tanabe Pharma, Mochida Pharmaceutical Co., Ltd., and Zeria Pharmaceutical Co., Ltd.
Kobayashi T has received 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 Pharmaceutical Co., Ltd.; 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.
Feagan BG has received consulting and/or speaker fees from AbbVie, AdMIRx, AgomAB Therapeutics, Akebia, Alivio Therapeutics, Allakos, Amgen, Applied Molecular Transport Inc., Arena Pharma, Avir, Azora Therapeutics, Boehringer Ingelheim, Boston Pharma, Celgene/BMS, Connect BioPharma, Cytoki, Disc Medicine, Eli Lilly, Equillium, Everest Clinical Research Corp., Ferring, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Glenmark, Gossamer Pharma, GSK, Hoffmann-La Roche, Hot Spot Therapeutics, ImmuNext, Index Pharma, Intact Therapeutics, Janssen, Japan Tobacco Inc., Kaleido Biosciences, Leadiant, Millennium, MiroBio, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Otsuka, Pandion Therapeutics, Pfizer, Progenity, Prometheus Therapeutics and Diagnostics, PTM Therapeutics, Q32 Bio, Rebiotix, RedHill Biopharma, REDX, Sandoz, Sanofi, Seres Therapeutics, Surrozen Inc., Takeda, Teva, Thelium, Theravance, Tigenix, Tillotts, UCB Pharma, VHsquared Ltd., Viatris, Ysios, and Zealand Pharma.
Tasset C and Besuyen R are employees and shareholders of Galapagos.
Yun C, Crans G, and Zhang J are employees and shareholders of Gilead Sciences, Inc.
Kondo A is an employee of Gilead Sciences K.K. and shareholder of Gilead Sciences, Inc.
Watanabe M has received grants from Alfresa Pharma Corporation, JIMRO Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., and Miyarisan Pharmaceutical Co., Ltd.; grants and personal fees from AbbVie GK, Astellas Pharma Inc., EA Pharma Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Zeria Pharmaceutical Co., Ltd.; and personal fees from Celgene K.K., Celltrion Healthcare Co., Ltd., Eli Lilly Japan K.K., Gilead Sciences, Inc., and Janssen Pharmaceutical K.K.
Hibi T, Matsuoka K, and Watanabe M are editorial board members of the journal but were not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.
Data Availability Statement
Anonymized individual patient data will be shared upon request for research purposes dependent upon the nature of the request, the merit of the proposed research, the availability of the data, and its intended use. The full data-sharing policy for Gilead Sciences, Inc., can be found at https://www.gilead.com/about/ethics-and-code-of-conduct/policies.
Author Contribution
Conceptualization: Tasset C, Yun C. Data curation: all authors. Formal analysis: Zhang J, Crans G. Investigation: Hibi T, Motoya S, Hisamatsu T, Hirai F, Watanabe K, Matsuoka K, Saruta M, Kobayashi T, Feagan BG, Watanabe M. Writing - review & editing: all authors. Approval of final manuscript: all authors.
Others
Medical writing support for the preparation of this manuscript was provided by Frances Thompson, PhD, of PharmaGenesis London, London, UK, and funded by Gilead Sciences K.K. (Tokyo, Japan).
Characteristics |
Induction study A: biologic-naïve patients |
Induction study B: biologic-experienced patients |
||||
---|---|---|---|---|---|---|
Placebo (n=6) | Filgotinib 100 mg (n=16) | Filgotinib 200 mg (n=15) | Placebo (n=14) | Filgotinib 100 mg (n=29) | Filgotinib 200 mg (n=29) | |
Age (yr), mean ± SD | 48 ± 11 | 48 ± 13 | 52 ± 12 | 49 ± 16 | 39 ± 14 | 45 ± 17 |
Female sex | 0 | 5 (31.3) | 8 (53.3) | 6 (42.9) | 6 (20.7) | 10 (34.5) |
Body weight (kg), median (Q1–Q3) | 61.7 (60.0–64.4) | 60.3 (57.0–70.7) | 62.2 (52.0–64.2) | 58.0 (47.5–63.5) | 59.2 (56.6–67.5) | 56.7 (51.8–65.0) |
BMI (kg/m2), median (Q1–Q3) | 20.6 (20.2–21.9) | 21.7 (20.3–23.6) | 21.8 (20.4–23.3) | 21.2 (19.7–23.2) | 20.6 (18.5–23.9) | 21.5 (20.3–22.9) |
Smoking status | ||||||
Former | 3 (50.0) | 9 (56.3) | 8 (53.3) | 7 (50.0) | 12 (41.4) | 10 (34.5) |
Current | 0 | 2 (12.5) | 1 (6.7) | 0 | 4 (13.8) | 1 (3.4) |
Never | 3 (50.0) | 5 (31.3) | 6 (40.0) | 7 (50.0) | 13 (44.8) | 18 (62.1) |
Duration of UC (yr), mean ± SD | 11.8 ± 14.0 | 8.2 ± 9.5 | 7.2 ± 6.8 | 9.5 ± 8.3 | 9.4 ± 7.4 | 9.2 ± 7.7 |
Total Mayo Clinic score, mean ± SD | 8.7 ± 2.1 | 8.0 ± 1.3 | 8.5 ± 1.1 | 8.9 ± 1.4 | 9.2 ± 1.0 | 8.5 ± 1.4 |
MES of 3 | 5 (83.3) | 9 (56.3) | 10 (66.7) | 13 (92.9) | 23 (79.3) | 25 (86.2) |
C-reactive protein (mg/L), mean ± SD | 6.2 ± 10.1 | 4.1 ± 6.7 | 4.1 ± 5.1 | 3.4 ± 4.3 | 6.9 ± 10.8 | 7.0 ± 11.4 |
Fecal calprotectin (μg/g), mean ± SD | 6,670 ± 8,295 | 1,995 ± 1,448 | 3,556 ± 3,348 | 1,685 ± 1,332 | 1,399 ± 1,218 | 2,352 ± 2,484 |
Concomitant use of systemic corticosteroidsa | 2 (33.3) | 4 (25.0) | 6 (40.0) | 4 (28.6) | 5 (17.2) | 6 (20.7) |
Concomitant use of immunosuppressantsa,b | 2 (33.3) | 6 (37.5) | 4 (26.7) | 3 (21.4) | 7 (24.1) | 7 (24.1) |
Concomitant use of systemic corticosteroids and immunosuppressants | 1 (16.7) | 2 (12.5) | 1 (6.7) | 2 (14.3) | 5 (17.2) | 5 (17.2) |
Prednisone-equivalent dose (mg/day), median (Q1–Q3) | 5.0 (2.5–10.0) | 10.0 (10.0–20.0) | 5.0 (2.5–10.0) | 5.0 (5.0–10.0) | 7.5 (5.0–20.0) | 10.0 (5.0–15.0) |
Concomitant use of 5-ASA | 5 (83.3) | 13 (81.3) | 12 (80.0) | 11 (78.6) | 26 (89.7) | 24 (82.8) |
Number of prior biologic agents used | ||||||
0 | 6 (100.0) | 16 (100.0) | 15 (100.0) | 0 | 0 | 0 |
1 | 0 | 0 | 0 | 7 (50.0) | 13 (44.8) | 13 (44.8) |
2 | 0 | 0 | 0 | 4 (28.6) | 15 (51.7) | 10 (34.5) |
≥3 | 0 | 0 | 0 | 3 (21.4) | 1 (3.4) | 6 (20.7) |
Prior use of at least 1 TNF antagonist | 0 | 0 | 0 | 13 (92.9) | 28 (96.6) | 29 (100.0) |
Prior use of vedolizumab | 0 | 0 | 0 | 4 (28.6) | 5 (17.2) | 3 (10.3) |
Prior use of at least 1 TNF antagonist and vedolizumab | 0 | 0 | 0 | 3 (21.4) | 4 (13.8) | 3 (10.3) |
Prior failure of at least 1 TNF antagonist | 0 | 0 | 0 | 13 (92.9) | 25 (86.2) | 25 (86.2) |
Prior failure of vedolizumab | 0 | 0 | 0 | 1 (7.1) | 2 (6.9) | 1 (3.4) |
Values are presented as number (%) unless otherwise indicated.
a Corticosteroids or immunosuppressants, but not both.
b 6-Mercaptopurine, azathioprine, and methotrexate.
SD, standard deviation; Q1, first quartile; Q3, third quartile; BMI, body mass index; UC, ulcerative colitis; MES, Mayo endoscopic subscore; 5-ASA, 5-aminosalicylates; TNF, tumor necrosis factor.
Outcomes | Placebo (n = 20) | Filgotinib 100 mg (n = 45) | Filgotinib 200 mg (n = 44) | ||
---|---|---|---|---|---|
Treatment-emergent AEs, No. (%) | |||||
AEs | 11 (55.0) | 23 (51.1) | 24 (54.5) | ||
Serious AEs | 3 (15.0) | 2 (4.4) | 1 (2.3) | ||
AEs leading to study drug discontinuation | 3 (15.0) | 1 (2.2) | 1 (2.3) | ||
Deaths | 0 | 0 | 0 | ||
AEs of interest, No. (%) | |||||
Infections | 3 (15.0) | 7 (15.6) | 8 (18.2) | ||
Serious infections | 0 | 0 | 0 | ||
Herpes zoster | 0 | 0 | 1 (2.3)a | ||
Opportunistic infections | 0 | 0 | 0 | ||
Malignancies excluding non-melanoma skin cancers | 0 | 1 (2.2)b | 0 | ||
Non-melanoma skin cancers | 0 | 0 | 0 | ||
Gastrointestinal perforation | 0 | 0 | 0 | ||
Venous thrombosis excluding pulmonary embolism | 0 | 0 | 0 | ||
Pulmonary embolism | 0 | 0 | 0 | ||
Arterial thrombosis | 0 | 0 | 0 | ||
Cerebrovascular events | 0 | 0 | 0 | ||
Grade 3–4 laboratory abnormalities, No. (%) | |||||
Hematology | |||||
Decreased hemoglobin | 1 (5.0) | 1 (2.2) | 1 (2.3) | ||
Decreased WBC | 0 | 0 | 0 | ||
Decreased neutrophils | 0 | 0 | 0 | ||
Decreased lymphocytes | 0 | 2 (4.4) | 0 | ||
Chemistry | |||||
Increased AST | 0 | 0 | 0 | ||
Increased ALT | 0 | 0 | 0 | ||
Increased creatine kinase | 0 | 0 | 0 | ||
Decreased phosphorus | 0 | 0 | 2 (4.5) | ||
Fasting HDL/LDL cholesterol value change from baseline at week 10, mean ± SD | |||||
LDL cholesterol (mg/dL) | 10 ± 22 | 12 ± 23 | 18 ± 30 | ||
HDL cholesterol (mg/dL) | 4 ± 17 | 15 ± 15 | 23 ± 18 | ||
LDL:HDL ratio | 0.1 ± 0.4 | −0.2 ± 0.3 | −0.3 ± 0.4 |
a A 56-year-old man in induction study A with grade 2 herpes zoster.
b A 64-year-old man in induction study A with grade 3 colon cancer.
Induction study A, biologic-naïve patients; Induction study B, biologic-experienced patients; AE, adverse event; WBC, white blood cells; AST, aspartate aminotransferase; ALT, alanine aminotransferase; HDL, high-density lipoprotein; LDL, low-density lipoprotein; SD, standard deviation.
Outcomes | Placebo (n=5)a | Placebo (n=6)b | Filgotinib 100 mg (n=14)c | Placebo (n=9)d | Filgotinib 200 mg (n=20)e | ||
---|---|---|---|---|---|---|---|
AEs, No. (%) | |||||||
AEs | 5 (100.0) | 4 (66.7) | 10 (71.4) | 7 (77.8) | 16 (80.0) | ||
Serious AEs | 0 | 1 (16.7) | 1 (7.1) | 0 | 1 (5.0) | ||
AEs leading to study drug discontinuation | 0 | 0 | 2 (14.3) | 0 | 0 | ||
Deaths | 0 | 0 | 0 | 0 | 0 | ||
AEs of interest, No. (%) | |||||||
Infections | 4 (80.0) | 2 (33.3) | 6 (42.9) | 3 (33.3) | 10 (50.0) | ||
Serious infections | 0 | 0 | 0 | 0 | 0 | ||
Herpes zoster | 0 | 0 | 0 | 0 | 1 (5.0)f | ||
Opportunistic infections | 0 | 0 | 0 | 0 | 0 | ||
Malignancies excluding non-melanoma skin cancers | 0 | 0 | 1 (7.1)g | 0 | 0 | ||
Non-melanoma skin cancers | 0 | 0 | 0 | 0 | 0 | ||
Gastrointestinal perforation | 0 | 0 | 0 | 0 | 0 | ||
Venous thrombosis excluding pulmonary embolism | 0 | 0 | 0 | 0 | 0 | ||
Pulmonary embolism | 0 | 0 | 0 | 0 | 0 | ||
Arterial thrombosis | 0 | 0 | 0 | 0 | 0 | ||
Cerebrovascular events | 0 | 0 | 0 | 0 | 0 | ||
Grade 3–4 laboratory abnormalities, No. (%) | |||||||
Hematology | |||||||
Decreased hemoglobin | 0 | 0 | 0 | 0 | 0 | ||
Decreased WBC | 0 | 0 | 0 | 0 | 0 | ||
Decreased neutrophils | 0 | 0 | 0 | 0 | 0 | ||
Decreased lymphocytes | 0 | 1 (16.7) | 0 | 0 | 2 (10.0) | ||
Chemistry | |||||||
Increased AST | 0 | 0 | 0 | 0 | 0 | ||
Increased ALT | 0 | 0 | 0 | 0 | 0 | ||
Increased creatine kinase | 0 | 0 | 0 | 0 | 0 | ||
Decreased phosphorus | 0 | 0 | 0 | 0 | 0 | ||
Fasting HDL/LDL cholesterol value change from baseline at week 58, mean ± SD | |||||||
Number | 2 | 3 | 8 | 1 | 14 | ||
LDL cholesterol, mg/dL | −12 ± 23 | 1 ± 41 | 16 ± 23 | 18 | 1 ± 31 | ||
HDL cholesterol, mg/dL | −19 ± 26 | −11 ± 15 | 4 ± 8 | −14 | −8 ± 19 | ||
LDL:HDL ratio | 0.2 ± 0.2 | 0.2 ± 0.3 | 0.1 ± 0.4 | 0.9 | 0.2 ± 0.4 |
a Patients who responded with placebo in the induction studies and continued to receive placebo in the maintenance study.
b Patients who responded with filgotinib 100 mg in the induction studies and were randomly assigned to placebo in the maintenance study.
c Patients who responded with filgotinib 100 mg in the induction studies and were randomly assigned to filgotinib 100 mg in the maintenance study.
d Patients who responded with filgotinib 200 mg in the induction studies and were randomly assigned to placebo in the maintenance study.
e Patients who responded with filgotinib 200 mg in the induction studies and were randomly assigned to filgotinib 200 mg in the maintenance study.
f A 62-year-old woman with grade 2 herpes zoster.
g The same patient (64-year-old man) who had colon cancer in induction study A had colon cancer during the maintenance study.
Induction study A, biologic-naïve patients; Induction study B, biologic-experienced patients; AE, adverse event; WBC, white blood cells; AST, aspartate aminotransferase; ALT, alanine aminotransferase; HDL, high-density lipoprotein; LDL, low-density lipoprotein; SD, standard deviation.
Characteristics | Induction study A: biologic-naïve patients |
Induction study B: biologic-experienced patients |
||||
---|---|---|---|---|---|---|
Placebo (n=6) | Filgotinib 100 mg (n=16) | Filgotinib 200 mg (n=15) | Placebo (n=14) | Filgotinib 100 mg (n=29) | Filgotinib 200 mg (n=29) | |
Age (yr), mean ± SD | 48 ± 11 | 48 ± 13 | 52 ± 12 | 49 ± 16 | 39 ± 14 | 45 ± 17 |
Female sex | 0 | 5 (31.3) | 8 (53.3) | 6 (42.9) | 6 (20.7) | 10 (34.5) |
Body weight (kg), median (Q1–Q3) | 61.7 (60.0–64.4) | 60.3 (57.0–70.7) | 62.2 (52.0–64.2) | 58.0 (47.5–63.5) | 59.2 (56.6–67.5) | 56.7 (51.8–65.0) |
BMI (kg/m2), median (Q1–Q3) | 20.6 (20.2–21.9) | 21.7 (20.3–23.6) | 21.8 (20.4–23.3) | 21.2 (19.7–23.2) | 20.6 (18.5–23.9) | 21.5 (20.3–22.9) |
Smoking status | ||||||
Former | 3 (50.0) | 9 (56.3) | 8 (53.3) | 7 (50.0) | 12 (41.4) | 10 (34.5) |
Current | 0 | 2 (12.5) | 1 (6.7) | 0 | 4 (13.8) | 1 (3.4) |
Never | 3 (50.0) | 5 (31.3) | 6 (40.0) | 7 (50.0) | 13 (44.8) | 18 (62.1) |
Duration of UC (yr), mean ± SD | 11.8 ± 14.0 | 8.2 ± 9.5 | 7.2 ± 6.8 | 9.5 ± 8.3 | 9.4 ± 7.4 | 9.2 ± 7.7 |
Total Mayo Clinic score, mean ± SD | 8.7 ± 2.1 | 8.0 ± 1.3 | 8.5 ± 1.1 | 8.9 ± 1.4 | 9.2 ± 1.0 | 8.5 ± 1.4 |
MES of 3 | 5 (83.3) | 9 (56.3) | 10 (66.7) | 13 (92.9) | 23 (79.3) | 25 (86.2) |
C-reactive protein (mg/L), mean ± SD | 6.2 ± 10.1 | 4.1 ± 6.7 | 4.1 ± 5.1 | 3.4 ± 4.3 | 6.9 ± 10.8 | 7.0 ± 11.4 |
Fecal calprotectin (μg/g), mean ± SD | 6,670 ± 8,295 | 1,995 ± 1,448 | 3,556 ± 3,348 | 1,685 ± 1,332 | 1,399 ± 1,218 | 2,352 ± 2,484 |
Concomitant use of systemic corticosteroids |
2 (33.3) | 4 (25.0) | 6 (40.0) | 4 (28.6) | 5 (17.2) | 6 (20.7) |
Concomitant use of immunosuppressants |
2 (33.3) | 6 (37.5) | 4 (26.7) | 3 (21.4) | 7 (24.1) | 7 (24.1) |
Concomitant use of systemic corticosteroids and immunosuppressants | 1 (16.7) | 2 (12.5) | 1 (6.7) | 2 (14.3) | 5 (17.2) | 5 (17.2) |
Prednisone-equivalent dose (mg/day), median (Q1–Q3) | 5.0 (2.5–10.0) | 10.0 (10.0–20.0) | 5.0 (2.5–10.0) | 5.0 (5.0–10.0) | 7.5 (5.0–20.0) | 10.0 (5.0–15.0) |
Concomitant use of 5-ASA | 5 (83.3) | 13 (81.3) | 12 (80.0) | 11 (78.6) | 26 (89.7) | 24 (82.8) |
Number of prior biologic agents used | ||||||
0 | 6 (100.0) | 16 (100.0) | 15 (100.0) | 0 | 0 | 0 |
1 | 0 | 0 | 0 | 7 (50.0) | 13 (44.8) | 13 (44.8) |
2 | 0 | 0 | 0 | 4 (28.6) | 15 (51.7) | 10 (34.5) |
≥3 | 0 | 0 | 0 | 3 (21.4) | 1 (3.4) | 6 (20.7) |
Prior use of at least 1 TNF antagonist | 0 | 0 | 0 | 13 (92.9) | 28 (96.6) | 29 (100.0) |
Prior use of vedolizumab | 0 | 0 | 0 | 4 (28.6) | 5 (17.2) | 3 (10.3) |
Prior use of at least 1 TNF antagonist and vedolizumab | 0 | 0 | 0 | 3 (21.4) | 4 (13.8) | 3 (10.3) |
Prior failure of at least 1 TNF antagonist | 0 | 0 | 0 | 13 (92.9) | 25 (86.2) | 25 (86.2) |
Prior failure of vedolizumab | 0 | 0 | 0 | 1 (7.1) | 2 (6.9) | 1 (3.4) |
Outcomes | Placebo (n = 20) | Filgotinib 100 mg (n = 45) | Filgotinib 200 mg (n = 44) | ||
---|---|---|---|---|---|
Treatment-emergent AEs, No. (%) | |||||
AEs | 11 (55.0) | 23 (51.1) | 24 (54.5) | ||
Serious AEs | 3 (15.0) | 2 (4.4) | 1 (2.3) | ||
AEs leading to study drug discontinuation | 3 (15.0) | 1 (2.2) | 1 (2.3) | ||
Deaths | 0 | 0 | 0 | ||
AEs of interest, No. (%) | |||||
Infections | 3 (15.0) | 7 (15.6) | 8 (18.2) | ||
Serious infections | 0 | 0 | 0 | ||
Herpes zoster | 0 | 0 | 1 (2.3) |
||
Opportunistic infections | 0 | 0 | 0 | ||
Malignancies excluding non-melanoma skin cancers | 0 | 1 (2.2) |
0 | ||
Non-melanoma skin cancers | 0 | 0 | 0 | ||
Gastrointestinal perforation | 0 | 0 | 0 | ||
Venous thrombosis excluding pulmonary embolism | 0 | 0 | 0 | ||
Pulmonary embolism | 0 | 0 | 0 | ||
Arterial thrombosis | 0 | 0 | 0 | ||
Cerebrovascular events | 0 | 0 | 0 | ||
Grade 3–4 laboratory abnormalities, No. (%) | |||||
Hematology | |||||
Decreased hemoglobin | 1 (5.0) | 1 (2.2) | 1 (2.3) | ||
Decreased WBC | 0 | 0 | 0 | ||
Decreased neutrophils | 0 | 0 | 0 | ||
Decreased lymphocytes | 0 | 2 (4.4) | 0 | ||
Chemistry | |||||
Increased AST | 0 | 0 | 0 | ||
Increased ALT | 0 | 0 | 0 | ||
Increased creatine kinase | 0 | 0 | 0 | ||
Decreased phosphorus | 0 | 0 | 2 (4.5) | ||
Fasting HDL/LDL cholesterol value change from baseline at week 10, mean ± SD | |||||
LDL cholesterol (mg/dL) | 10 ± 22 | 12 ± 23 | 18 ± 30 | ||
HDL cholesterol (mg/dL) | 4 ± 17 | 15 ± 15 | 23 ± 18 | ||
LDL:HDL ratio | 0.1 ± 0.4 | −0.2 ± 0.3 | −0.3 ± 0.4 |
Outcomes | Placebo (n=5) |
Placebo (n=6) |
Filgotinib 100 mg (n=14) |
Placebo (n=9) |
Filgotinib 200 mg (n=20) |
||
---|---|---|---|---|---|---|---|
AEs, No. (%) | |||||||
AEs | 5 (100.0) | 4 (66.7) | 10 (71.4) | 7 (77.8) | 16 (80.0) | ||
Serious AEs | 0 | 1 (16.7) | 1 (7.1) | 0 | 1 (5.0) | ||
AEs leading to study drug discontinuation | 0 | 0 | 2 (14.3) | 0 | 0 | ||
Deaths | 0 | 0 | 0 | 0 | 0 | ||
AEs of interest, No. (%) | |||||||
Infections | 4 (80.0) | 2 (33.3) | 6 (42.9) | 3 (33.3) | 10 (50.0) | ||
Serious infections | 0 | 0 | 0 | 0 | 0 | ||
Herpes zoster | 0 | 0 | 0 | 0 | 1 (5.0) |
||
Opportunistic infections | 0 | 0 | 0 | 0 | 0 | ||
Malignancies excluding non-melanoma skin cancers | 0 | 0 | 1 (7.1) |
0 | 0 | ||
Non-melanoma skin cancers | 0 | 0 | 0 | 0 | 0 | ||
Gastrointestinal perforation | 0 | 0 | 0 | 0 | 0 | ||
Venous thrombosis excluding pulmonary embolism | 0 | 0 | 0 | 0 | 0 | ||
Pulmonary embolism | 0 | 0 | 0 | 0 | 0 | ||
Arterial thrombosis | 0 | 0 | 0 | 0 | 0 | ||
Cerebrovascular events | 0 | 0 | 0 | 0 | 0 | ||
Grade 3–4 laboratory abnormalities, No. (%) | |||||||
Hematology | |||||||
Decreased hemoglobin | 0 | 0 | 0 | 0 | 0 | ||
Decreased WBC | 0 | 0 | 0 | 0 | 0 | ||
Decreased neutrophils | 0 | 0 | 0 | 0 | 0 | ||
Decreased lymphocytes | 0 | 1 (16.7) | 0 | 0 | 2 (10.0) | ||
Chemistry | |||||||
Increased AST | 0 | 0 | 0 | 0 | 0 | ||
Increased ALT | 0 | 0 | 0 | 0 | 0 | ||
Increased creatine kinase | 0 | 0 | 0 | 0 | 0 | ||
Decreased phosphorus | 0 | 0 | 0 | 0 | 0 | ||
Fasting HDL/LDL cholesterol value change from baseline at week 58, mean ± SD | |||||||
Number | 2 | 3 | 8 | 1 | 14 | ||
LDL cholesterol, mg/dL | −12 ± 23 | 1 ± 41 | 16 ± 23 | 18 | 1 ± 31 | ||
HDL cholesterol, mg/dL | −19 ± 26 | −11 ± 15 | 4 ± 8 | −14 | −8 ± 19 | ||
LDL:HDL ratio | 0.2 ± 0.2 | 0.2 ± 0.3 | 0.1 ± 0.4 | 0.9 | 0.2 ± 0.4 |
Values are presented as number (%) unless otherwise indicated. Corticosteroids or immunosuppressants, but not both. 6-Mercaptopurine, azathioprine, and methotrexate. SD, standard deviation; Q1, first quartile; Q3, third quartile; BMI, body mass index; UC, ulcerative colitis; MES, Mayo endoscopic subscore; 5-ASA, 5-aminosalicylates; TNF, tumor necrosis factor.
A 56-year-old man in induction study A with grade 2 herpes zoster. A 64-year-old man in induction study A with grade 3 colon cancer. Induction study A, biologic-naïve patients; Induction study B, biologic-experienced patients; AE, adverse event; WBC, white blood cells; AST, aspartate aminotransferase; ALT, alanine aminotransferase; HDL, high-density lipoprotein; LDL, low-density lipoprotein; SD, standard deviation.
Patients who responded with placebo in the induction studies and continued to receive placebo in the maintenance study. Patients who responded with filgotinib 100 mg in the induction studies and were randomly assigned to placebo in the maintenance study. Patients who responded with filgotinib 100 mg in the induction studies and were randomly assigned to filgotinib 100 mg in the maintenance study. Patients who responded with filgotinib 200 mg in the induction studies and were randomly assigned to placebo in the maintenance study. Patients who responded with filgotinib 200 mg in the induction studies and were randomly assigned to filgotinib 200 mg in the maintenance study. A 62-year-old woman with grade 2 herpes zoster. The same patient (64-year-old man) who had colon cancer in induction study A had colon cancer during the maintenance study. Induction study A, biologic-naïve patients; Induction study B, biologic-experienced patients; AE, adverse event; WBC, white blood cells; AST, aspartate aminotransferase; ALT, alanine aminotransferase; HDL, high-density lipoprotein; LDL, low-density lipoprotein; SD, standard deviation.