Résumé
Abstract
Background
Filgotinib (FIL) is an oral, selective janus kinase 1 inhibitor under development for the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. Safety and efficacy of FIL was investigated in the FINCH clinical program, which includes three Phase 3, summarized, summarized studies in patients with moderate to severely active RA. FINCH1: patients with inadequate response to MTX (NCT02889796); FINCH2: patients receiving conventional disease-modifying antirheumatic drugs (csDMARDs) with inadequate response to biological DMARDs (NCT02873936); FINCH3: MTX-naïve patients initiating MTX ± FIL, or receiving FIL monotherapy (NCT02886728). We present pooled safety data up to 24 weeks (W24).
Methods
The FINCH studies enrolled patients with RA (2010 ACR/EULAR criteria), ≥6 swollen joints and ≥6 tender joints at screening and Day 1. Safety analyses included patients receiving ≥1 dose of study drug. Patients in FINCH 1 and 2 who did not experience at least a 20% improvement in both swollen joint count and tender joint count by W14 discontinued study drug and switched to standard of care. W24 safety data from all studies were aggregated and ummarized. Key safety endpoints were treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of interest, deaths and treatment-emergent laboratory abnormalities.
Results
3,452 patients were evaluated; 2,088 received FIL. At W24, the frequency of TEAEs and TEAEs of interest were similar for those who received FIL and those in the control groups (Table 1). Most TEAEs were infections. Laboratory abnormality rates were similar between FIL and control groups, and were mild to moderate (grades 1 and 2). Overall, the frequency of major adverse cardiac events, herpes zoster virus, deep vein thrombosis and pulmonary embolism was low, and similar across groups.
O09 Table 1
Frequency of treatment-emergent Aes and all deaths across FINCH 1-3 Phase 3 studies (Day 1 – Week 24)
n (%)
Placebo + MTX/csDMARD N = 1,039
ADA 40mg + MTX N = 325
FIL 100 mg + MTX/csDMARD N = 840
FIL 200 mg + MTX/csDMARD N = 1,038
FIL 200 mg N = 210
FIL Total N = 2,088
Treatment-emergent AE
614 (59.1)
185 (56.9)
527 (62.7)
663 (63.9)
113 (53.8)
1303 (62.4)
Treatment-emergent serious AE
37 (3.6)
14 (4.3)
37 (4.4)
44 (4.2)
10 (4.8)
91 (4.4)
Treatment-emergent AE of Interest
253 (24.4)
91 (28.0)
232 (27.6)
289 (27.8)
54 (25.7)
575 (27.5)
Infectious AE
244 (23.5)
88 (27.1)
229 (27.3)
283 (27.3)
53 (25.2)
565 (27.1)
Serious Infectious AE
10 (1.0)
8 (2.5)
13 (1.5)
13 (1.3)
3 (1.4)
29 (1.4)
Herpes Zoster
4 (0.4)
2 (0.6)
5 (0.6)
6 (0.6)
1 (0.5)
12 (0.6)
Hepatitis B or C
1 (<0.1)
1 (0.3)
0
2 (0.2)
0
2 (<0.1)
Opportunistic Infections
0
1 (0.3)
0
1 (<0.1)
0
1 (<0.1)
Active TB
0
0
0
0
0
0
MACE
5 (0.5)
1 (0.3)
2 (0.2)
2 (0.2)
1 (0.5)
5 (0.2)
DVT/PE
3 (0.3)
0
0
1 (<0.1)#
0
1 (<0.1)#
Malignancy Excluding NMSC
4 (0.4)
1 (0.3)
1 (0.1)
0
0
1 (<0.1)
NMSC
0
0
0
1 (<0.1)
0
1 (<0.1)
Gastrointestinal Perforations
0
0
0
0
0
0
Death
2 (0.2)
0
1 (0.1)
3 (0.3)
0
4 (0.2)
ADA, adalimumab; csDMARD, conventional synthetic DMARD; DVT, deep vein thrombosis; FIL, filgotinib; MACE, major adverse cardiac event; NMSC, Nonmelanoma Skin Cancer; PBO, placebo; PE, pulmonary embolism; TB, tuberculosis. # excludes one event of retinal vein occlusion.
Conclusion
Pooled data from this large database highlights the favourable safety and tolerability profile of FIL in patients with RA both as monotherapy and in combination with MTX/csDMARD.
Disclosures
D. Walker: Other; Received support from Lilly, Pfizer, Novartis and Roche. K. Winthrop: Grants/research support; Received grants for clinical research from Bristol-Myers Squibb Company and Insmed Incorporated. Other; Received support from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Eli Lilly & Co., MSD, Novartis, Pfizer, Roche-Chugai, Sanofi, and UCB. M.C. Genovese: Other; Gilead Sciences Inc., Galapagos NV, AbbVie Inc. Eli Lilly and Company, Pfizer. B.G. Combe: Honoraria; Honoraria from AbbVie, BMS, Gilead, Janssen, Eli Lilly and Co., MSD, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB. Y. Tanaka: Honoraria; Received from Daiichi-Sankyo, Astellas, Chugai, Eli Lilly and Co., Pfizer, AbbVie, YL Biologics, BMS, Takeda, Misubishi-Tanabe, Novartis, Eisai, Janssen, Teijin. Grants/research support; Received grant support from Asahi-Kasei, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, BMS, UCB, Daiichi-Sankyo, Eisai, and Ono. A. Kivitiz: Consultancies; Consultant for AbbVie, Celgene, Horizon, Janssen, Merck, Novartis, Pfizer, UCB, Genzyme,Sanofi, Regeneron, SUN Pharma Advanced Research, Boehringer Ingelheim and Flexion. Shareholder/stock ownership; Shareholder of Novartis. F. Matzkies: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. B. Bartok: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. L. Ye: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. Y. Guo: Corporate appointments; Gilead Sciences, Inc. Shareholder/stock ownership; Gilead Sciences, Inc. C. Tasset: Corporate appointments; Employee of Galapagos NV. J.S. Sundy: Corporate appointments; Employee of Gilead Sciences, Inc. Shareholder/stock ownership; Shareholder of Gilead Sciences, Inc. E. Keystone: Consultancies; AbbVie, Amgen, AstraZeneca Pharma, Biotest, BMS Canada, Celltrion, Crescendo, Bioscience, F.Hoffman-La Roche Inc., Genentech, Janssen, Eli Lilly and Co., Merck, Pfizer, PuraPharm, Sandoz,, Sanofi-Aventis, Sanofi- Genzyme Samsung Bioepsis, and UCB. Other; AbbVie, Amgen, AstraZeneca Pharma, Biotest, BMS Canada, Celltrion, Crescendo, Bioscience, F.Hoffman-La Roche Inc., Genentech, Janssen, Eli Lilly and Co., Merck, Pfizer, PuraPharm, Sandoz,, Sanofi-Aventis, Sanofi-Genzyme, Samsumg Bioepsis, and UCB. R. Westhovens: Corporate appointments; An investigator and advisor for Celltrion and Galapagos/Gilead. W. Rigby: Consultancies; Consultancy for Gilead. G.R. Burmester: Consultancies; Consultancy from AbbVie, Gilead, Eli Lilly, and Pfizer. Honoraria; Honoraria from AbbVie, Gilead, Eli Lilly, and Pfizer.