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Scientific Abstracts
Oral Presentations
Rheumatoid arthritis - non biologic treatment and small molecules
OP0126 INFECTIONS AND SERIOUS INFECTIONS IN THE FILGOTINIB RHEUMATOID ARTHRITIS PROGRAM
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  1. J. Galloway1,
  2. M. H. Buch2,
  3. K. Yamaoka3,
  4. C. Leatherwood4,
  5. A. Pechonkina5,
  6. I. Tiamiyu4,
  7. D. Jiang6,
  8. L. Ye6,
  9. R. Besuyen7,
  10. D. Aletaha8,
  11. K. Winthrop9
  1. 1King’s College London, Centre for Rheumatic Diseases, School of Immunology and Microbial Sciences, London, United Kingdom
  2. 2University of Manchester, Division of Musculoskeletal & Dermatological Sciences, Manchester, United Kingdom
  3. 3Kitasato University School of Medicine, Department of Rheumatology and Infectious Diseases, Kanagawa, Japan
  4. 4Gilead Sciences, Inc., Clinical Research, Foster City, United States of America
  5. 5Gilead Sciences, Inc., Inflammation and Respiratory Therapeutic Area, Foster City, United States of America
  6. 6Gilead Sciences, Inc., Biostatistics, Foster City, United States of America
  7. 7Galapagos BV, Clinical Development, Leiden, Netherlands
  8. 8Medical University of Vienna, Division of Rheumatology, Department of Medicine 3, Vienna, Austria
  9. 9Oregon Health and Science University, Division of Infectious Diseases, Portland, United States of America

Abstract

Background: The Janus kinase (JAK)-1 preferential inhibitor filgotinib (FIL) improved rheumatoid arthritis (RA) signs and symptoms in 3 phase (P)3 trials.1–3 Like other RA therapies, JAK inhibition is associated with increased infection rates.4

Objectives: To assess long-term safety across the FIL program regarding infections, including serious infections (SI).

Methods: Patients (pts) meeting 2010 ACR/EULAR RA criteria in pooled analysis of P2 DARWIN 1–2 (D1–2), P3 FINCH 1–3 (F1–3), and long-term extension studies (DARWIN 3, FINCH 4) were included. The placebo (PBO)-controlled as-randomised data set included pts receiving FIL 100 mg (FIL100), FIL 200 mg (FIL200), or PBO up to week (W)12 (D1–2, F1–2). The active-controlled as-randomised data set included pts receiving FIL100, FIL200, adalimumab (ADA), or methotrexate (MTX) up to W52 (F1, F3). The long-term as-treated data set included pts in all 7 studies receiving FIL100 or FIL200; data after rerandomisation were included and contributed to treatment received.

Exposure-adjusted incidence rates (EAIRs) per 100 patient-years exposure (PYE) and differences with 95% confidence intervals (CIs) were calculated using Poisson regression; EAIRs for tuberculosis (TB) in active controlled sets were calculated using an Exact Poisson method. Kaplan-Meier (KM) event probabilities with 95% CIs were provided for SI. If pts had multiple events within the same treatment period, only the first event was counted in EAIR calculation; PYE were calculated up to the last follow-up time or day before next treatment, including after first event. For KM analysis, time to event was calculated until the first event.

Results: Of 2267/1647 pts in as-treated set receiving FIL200/FIL100, 1697 had treatment-emergent infection; 118 were SI. Baseline potential risk factors for pts with SI are in Table.

View this table:
Table 1.

Baseline characteristics of pts with/without treatment emergent SIa

In 12W PBO-controlled period, infection rates were 17.9%/15.6%/13.3% for FIL200/FIL100/PBO. In 52W ADA-controlled period, infection EAIRs (95% CIs)/100 PYE were 46.9 (40.9, 53.7)/43.7 (38.0, 50.4)/43.4 (36.5, 51.5), FIL200/FIL100/ADA; and 38.5 (33.8, 43.9)/39.0 (31.1, 48.8)/42.2 (36.1, 49.3), FIL200/FIL100/MTX in 52W MTX-controlled period; 24.8 (23.1, 26.5)/34.4 (30.4, 38.8), FIL200/FIL100 in long-term analysis. In 12W PBO-controlled period, there was no active TB for FIL200/FIL100/PBO. In 52W ADA-controlled period, active TB EAIRs (95% CIs)/100 PYE were: 0 (0.0, 0.8)/0 (0.0, 0.8)/0.3 (0.0, 1.9), FIL200/FIL100/ADA and 0 (0.0, 0.6)/0 (0.0, 1.9)/0 (0.0, 1.0), FIL200/FIL100/MTX in 52W MTX-controlled period; 0/0.1 (0.0, 0.5), FIL200/FIL100 in long-term analysis.

SI rate or EAIRs are in Figure. Most common infections were upper respiratory tract infection and nasopharyngitis; majority were low grade. Pneumonia was most common SI (<1%). In long-term population, event probability (95% CI) of SI was 2.2% (1.6, 2.9)/2.5% (1.8, 3.4) for FIL200/FIL100 at 52W. In F1–3 (excluding data after rerandomisation), there were no significant changes in mean neutrophil and lymphocyte counts; values remained within normal limits up to W52 for all arms.

Figure

Conclusion: EAIRs of infections and SI for FIL were similar to PBO, ADA, and MTX. At 52W, incidence rates of SI were comparable for FIL100 and FIL200. Long-term SI EAIR for FIL100 was slightly higher than for FIL200.

References: [1]Genovese et al. JAMA. 2019;322:315–25.

[2]Westhovens et al. Ann Rheum Dis. 2021; online first.

[3]Combe et al. Ann Rheum Dis. 2021; online first.

[4]Strand et al. Arthritis Res Ther. 2015;17:362.

Disclosure of Interests: James Galloway Speakers bureau: Pfizer, Bristol-Myers Squibb, UCB and Celgene, Maya H Buch Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi, Grant/research support from: Pfizer, Roche, and UCB, Kunihiro Yamaoka Speakers bureau: AbbVie, Actelion Pharmaceuticals Japan, Asahikasei Pharma Corp, Astellas Pharma, AYUMI Pharma Co, Boehringer Ingelheim Japan, Bristol-Myers Squibb, Chugai Pharma, Daiichi Sankyo, Eisai Pharma, Eli Lilly, GlaxoSmithKline, Gilead G.K., Hisamitsu Pharma Co., Janssen Pharma, Mitsubishi-Tanabe Pharma, MSD, Nippon Kayaku, Nippon Shinyaku, Ono Pharma, Otsuka Pharma, Pfizer, Sanofi, and Takeda Industrial Pharma, Consultant of: Asahikasei Pharma Corp., AbbVie, Gilead G.K., Pfizer, Astellas Pharma Inc, Eli Lilly Japan K.K., and Japan Tobacco Inc., Grant/research support from: Takeda Industrial Pharma, Pfizer, Astellas Pharma, Daiichi Sankyo, Eli Lilly, Eisai Pharma, Teijin Pharma, MSD, Shionogi, Chugai Pharma, Nippon Kayaku, Mitsubishi-Tanabe Pharma, and AbbVie, Cianna Leatherwood Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Iyabode Tiamiyu Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Deyuan Jiang Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Lei Ye Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Robin Besuyen Shareholder of: Galapagos BV, Employee of: Galapagos BV, Daniel Aletaha Speakers bureau: AbbVie, Celgene, Lilly, Merck, Novartis, Pfizer, Sanofi Genzyme, UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme, Grant/research support from: AbbVie, Novartis, Roche, Kevin Winthrop Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly and Co., Galapagos NV, Gilead Sciences, GlaxoSmithKline, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, and Pfizer

https://doi.org/10.1136/annrheumdis-2021-eular.1416

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