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POS0679 (2022)
CLINICAL OUTCOMES UP TO WEEK (W) 48 IN THE ONGOING FILGOTINIB (FIL) LONG-TERM EXTENSION (LTE) TRIAL OF RHEUMATOID ARTHRITIS (RA) PATIENTS (pts) WITH INADEQUATE RESPONSE (IR) TO METHOTREXATE (MTX) INITIALLY TREATED WITH FIL OR ADALIMUMAB (ADA) DURING THE PHASE 3 PARENT STUDY (PS)
B. Combe1, Y. Tanaka2, P. Emery3, A. Pechonkina4, A. Kuo4, Q. Gong5, K. Van Beneden6, V. Rajendran7, H. Schulze-Koops8
1University of Montpellier, Rheumatology Department, Montpellier, France
2University of Occupational and Environmental Health, The First Department of Internal Medicine, Fukuoka, Japan
3University of Leeds, Leeds NIHR Biomedical Research Centre, LIRMM, Leeds, United Kingdom
4Gilead Sciences, Inc., Clinical Development, Foster City, United States of America
5Gilead Sciences, Inc., Biostatistics, Foster City, United States of America
6Galapagos NV, Medical Affairs, Mechelen, Belgium
7Galapagos NV, Clinical Development, Mechelen, Belgium
8Ludwig-Maximilians-University, Division of Rheumatology and Clinical Immunology, Department of Medicine IV, Munich, Germany

Background: The preferential Janus kinase-1 inhibitor FIL is approved for treatment of moderate to severe active RA in Europe and Japan.


Objectives: Efficacy and safety of FIL were assessed in pts with IR to MTX who completed a Phase 3 trial (NCT02889796) 1 and enrolled in an LTE (NCT03025308).


Methods: Pts completing the PS 1 on study drug were eligible to enter the LTE (data cutoff: June 1, 2020). Median exposure: 2.2 years (y). Efficacy data to W48 are reported for 4 treatment groups (all with background MTX): pts receiving FIL 200 mg (FIL200) or FIL 100 mg (FIL100) in the PS and continuing their dose in LTE (FIL200/FIL200, FIL100/FIL100) and ADA pts rerandomized, double blind, to FIL200 or FIL100 for LTE (ADA/FIL200, ADA/FIL100); safety data are reported.


Results: As of June 1, 2020, 522/571 (91%) FIL200/FIL200, 502/570 (88%) FIL100/FIL100, 118/128 (92%) ADA/FIL200, and 115/130 (89%) ADA/FIL100 pts remained on study drug. LTE baseline disease characteristics were similar between groups: mean duration of RA approximately 8.7 y; DAS28(CRP) 2.55, and mean concurrent MTX dosage was 15.0 mg/week. Proportions of pts achieving ACR20/50/70, DAS28(CRP) ≤3.2, <2.6, and CDAI ≤10, ≤2.8 were generally maintained in all LTE groups through W48 ( Figure 1 ). Numerically greater proportions of pts met response criteria at W48 in the FIL200 groups vs FIL100, regardless of PS treatment. Treatment-emergent AEs (TEAE), serious AEs, and AEs Grade ≥3 were largely comparable between groups and lowest in ADA/FIL100. There were 10 deaths ( Table 1 ). Exposure-adjusted incidence rates (EAIRs)/100 pt-y of exposure for deaths were lower for FIL/FIL vs ADA/FIL.

EAIRs of TEAEs in LTE, as of June 1, 2020

1TEAE, n (%) 3FIL200+MTX → FIL200+MTX 6ADA+MTX → FIL200+MTX 9FIL100+MTX → FIL100+MTX 12ADA+MTX → FIL100+MTX
2EAIR (95% CI) 4n=571 7n=128 10n=570 13n=130
5PYE=859.4 8PYE=197.8 11PYE=852.3 14PYE=192.6
TEAE 429 (75.1) 91 (71.1) 443 (77.7) 88 (67.7)
49.9 (45.4, 54.9) 46.0 (37.5, 56.5) 52.0 (47.4, 57.0) 45.7 (37.1, 56.3)
TEAE Grade ≥3 64 (11.2) 15 (11.7) 72 (12.6) 7 (5.4)
7.4 (5.8, 9.5) 7.6 (4.6, 12.6) 8.4 (6.7, 10.6) 3.6 (1.7, 7.6)
TE serious AE 52 (9.1) 13 (10.2) 60 (10.5) 9 (6.9)
6.1 (4.6, 7.9) 6.6 (3.8, 11.3) 7.0 (5.5, 9.1) 4.7 (2.4, 9.0)
Death 3 (0.5) 2 (1.6) 3 (0.5) 2 (1.5)
0.3 (0.1, 1.1) 1.0 (0.3, 4.0) 0.4 (0.1, 1.1) 1.0 (0.3, 4.2)
TE infections 243 (42.6) 52 (40.6) 249 (43.7) 43 (33.1)
28.3 (24.9, 32.1) 26.3 (20.0, 34.5) 29.2 (25.8, 33.1) 22.3 (16.6, 30.1)
TE serious infections 7 (1.2) 2 (1.6) 13 (2.3) 1 (0.8)
0.8 (0.4, 1.7) 1.0 (0.3, 4.0) 1.5 (0.9, 2.6) 0.5 (0.1, 3.7)
Opportunistic infections 2 (0.4) 0 2 (0.4) 0
0.2 (0, 0.8) 0 (0, 1.9) 0.2 (0, 0.8) 0 (0, 1.9)
TE herpes zoster 16 (2.8) 5 (3.9) 13 (2.3) 1 (0.8)
1.9 (1.1, 3.0) 2.5 (1.1,6.1) 1.5 (0.9, 2.6) 0.5 (0.1, 3.7)
TE MACE (adjudicated) 1 (0.2) 0 3 (0.5) 3 (2.3)
01 (0, 0.6) 0 (0, 1.9) 0.4 (0.1, 1.1) 1.6 (0.5, 4.8)
TE DVT/PE (adjudicated) 3 (0.5) 0 3 (0.5) 0
0.3 (0.1, 1.0) 0 (0, 1.9) 0.4 (0.1, 1.0) 0 (0, 1.9)
Malignancies (excluding NMSC) 5 (0.9) 3 (2.3) 4 (0.7) 0
0.6 (0.2, 1.4) 1.5 (0.5, 4.7) 0.5 (0.1, 1.2) 0 (0, 1.9)
NMSC 3 (0.5) 0 2 (0.4) 0
0.3 (0.1, 1.0) 0 (0, 1.9) 0.2 (0, 0.8) 0 (0, 1.9)

DVT, deep vein thrombosis; MACE, major adverse cardiovascular event; NMSC, nonmelanoma skin cancer; PE, pulmonary embolism; TE, treatment-emergent


Conclusion: During the LTE through W48, response rates generally were maintained for FIL/FIL and ADA/FIL pts. Though there were differences between LTE groups, safety was largely comparable and consistent with PS observations 1 and previously reported results from 7 trials 2 : rates of AEs of special interest were low; all confidence intervals were overlapping. Limitation: the LTE was not formally randomized for comparison between FIL/FIL and ADA/FIL treatment groups, the groups were of unequal size, and the switch from ADA to FIL for LTE was by design, rather than based on disease activity.


REFERENCES:

[1]Combe B et al. Ann Rheum Dis 2021;80:848–58.

[2]Winthrop K et al. Arthritis Rheumatol 2020;72(suppl 10); abstract 0229.


Acknowledgements: This study was funded by Gilead Sciences, Inc., Foster City, CA. Medical writing support was provided by Claudine Bitel, PhD, of AlphaScientia, LLC, San Francisco, CA; and funded by Gilead Sciences, Inc., Foster City, CA.


Disclosure of Interests: Bernard Combe Speakers bureau: BMS, Eli Lilly & Co., Gilead Sciences, Inc., MSD, Pfizer, Roche-Chugai, and UCB, Consultant of: AbbVie, Eli Lilly & Co., Gilead Sciences, Inc., Janssen, Pfizer, Roche-Chugai, and Sanofi, Grant/research support from: Novartis, Pfizer, and Roche-Chugai, Yoshiya Tanaka Speakers bureau: AbbVie, Asahi-Kasei, Astellas, Bristol-Myers, Chugai, Daiichi- Sankyo, Eli Lilly, Eisai, Gilead, GSK, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Sanofi, and YL Biologics, Consultant of: AbbVie, Ayumi, Daiichi- Sankyo, Eli Lilly, GSK, Sanofi, and Taisho, Grant/research support from: AbbVie, Asahi-Kasei, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, and Takeda, Paul Emery Consultant of: AbbVie, BMS, Celltrion, Gilead, Lilly, Novartis, Roche, Samsung, and Sandoz, Grant/research support from: AbbVie, BMS, Lilly, and Samsung, Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Albert Kuo Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Qi Gong Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Katrien Van Beneden Shareholder of: Galapagos NV, Employee of: Galapagos NV, Vijay Rajendran Shareholder of: Galapagos NV, Employee of: Galapagos NV, Hendrik Schulze-Koops Speakers bureau: AbbVie, Amgen, BMS, Celgene, Celltrion, Chugai, Gilead, Janssen, Eli Lilly and Company, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, and Sanofi, Consultant of: AbbVie, Amgen, BMS, Celgene, Celltrion, Chugai, Gilead, Janssen, Eli Lilly and Company, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, and Sanofi, Grant/research support from: AbbVie and Novartis

Citation: , volume 81, supplement 1, year 2022, page 615
Session: Rheumatoid arthritis - non biologic treatment and small molecules (POSTERS only)