Pos0824 cardiovascular (cv) and malignancy events in the filgotinib (fil) rheumatoid arthritis (ra) clinical development program up to 8.3 years

Background FIL is a Janus kinase (JAK) 1 preferential inhibitor for the treatment of RA. Data from the ORAL Surveillance post-marketing study ( NCT02092467 ) suggest that in patients with active RA aged ≥50 years with ≥1 CV risk factor, the risks of cancer and major adverse cardiovascular events (MACE) are higher with the pan-JAK inhibitor tofacitinib vs tumor necrosis factor inhibitors, with higher rates in those aged ≥65 vs <65 years. [1] Objectives To assess the incidence of malignancies excluding non-melanoma skin cancer (NMSC), NMSC, MACE and venous thromboembolism (VTE) in patients treated with FIL 200 mg (FIL200) and FIL 100 mg (FIL100) in RA clinical trials. Methods Data were pooled from patients treated with FIL200 or FIL100 from DARWIN 1–3 ( NCT01888874 , NCT01894516 , NCT02065700 ) and FINCH 1–4 ( NCT02889796 , NCT02873936 , NCT02886728 , NCT03025308 ). Data cuts used for the ongoing DARWIN 3 and FINCH 4 studies were May 2, 2022, and May 6, 2022, respectively. Exposure-adjusted incidence rates (EAIRs) per 100 patient-years of exposure (PYE) were calculated for MACE, VTEs, malignancies excluding NMSC, NMSC and treatment-emergent adverse events (TEAEs) leading to death, according to FIL dose (200 vs 100 mg) and age (<65 vs ≥65 years); no statistical testing was performed, so all differences are numerical. MACE and VTE were adjudicated by an independent committee; the cutoff for adjudication was April 3, 2022. Results Overall, 3691 patients were treated with FIL for a total of 12,541 PYEs. Median (max) PYE was 3.8 (8.3) years for FIL200 and 3.3 (7.8) years for FIL100. Baseline characteristics are shown in the Table 1 . A greater proportion of those aged ≥65 years vs <65 years had a CV medical history in both the FIL200 (75.7% vs 36.1%) and FIL100 (71.8% vs 40.9%) groups. Overall EAIRs (95% confidence interval [CI]) were 0.40 (0.3, 0.5) for MACE, 0.19 (0.1, 0.3) for VTEs, 0.69 (0.6, 0.9) for malignancy excluding NMSC, 0.29 (0.2, 0.4) for NMSC and 0.65 (0.5, 0.8) for TEAEs leading to death. EAIRs of MACE and VTE were higher in patients aged ≥65 vs <65 years but were generally similar for FIL200 and FIL100 within each age group ( Figure 1 ). EAIRs of malignancies, NMSC and TEAEs leading to death were also higher in the ≥65- vs <65-year group. Within the ≥65-year group, EAIRs (95% CI) of these events were numerically higher in the FIL200 vs FIL100 group: 2.0 (1.3, 2.9) vs 0.99 (0.5, 1.9) for malignancies, 1.38 (0.8, 2.2) vs 0.44 (0.1, 1.1) for NMSC, and 1.59 (1.0, 2.5) vs 1.20 (0.6, 2.2) for TEAEs leading to death, respectively. Conclusion Rates of MACE and VTE in FIL-treated patients were low and similar for FIL200 and FIL100. There was a higher proportion of patients aged ≥65 years vs <65 years with a CV medical history. In patients aged ≥65 years, EAIRs of malignancies, NMSC and TEAEs leading to death were higher with FIL200 vs FIL100, although CIs overlapped. Reference [1]Ytterberg SR, et al. N Engl J Med 2022;386:316-26 Table 1. Baseline characteristics FIL200 FIL100 <65 y (n=1860) ≥65 y (n=407) <65 y (n=1321) ≥65 y (n=326) Age, y, mean (SD) 48.8 (10.7) 70.0 (4.4) 49.0 (10.5) 70.2 (4.5) Female, n (%) 1506 (81.0) 322 (79.1) 1075 (81.4) 244 (74.8) BMI, kg/m 2 , mean (SD) 27.5 (6.3) 28.1 (5.9) 27.7 (6.4) 27.2 (5.1) Creatinine clearance, mL/min, mean (SD) 122 (37.4) 84 (23.4) 122 (38.1) 83 (22.5) CRP, mg/L, mean (SD) 19.0 (24.3) 18.4 (25.2) 18.9 (25.9) 17.2 (24.7) Current smoker, n (%)* 207 (14.4) 37 (10.9) 165 (15.3) 28 (9.7) CV family history, n (%) † 43 (3.0) 10 (2.9) 47 (4.3) 12 (4.2) Any CV medical history, n (%) 672 (36.1) 308 (75.7) 540 (40.9) 234 (71.8) Current alcohol use, n (%)* 296 (20.6) 78 (22.9) 213 (19.7) 54 (18.7) *FIL200 <65 y: n=1436, ≥65 y: n=340; FIL100 <65 y: n=1081, ≥65 y: n=289. † FIL200 <65 y: n=1434, ≥65 y: n=339; FIL100 <65 y: n=1081, ≥65 y: n=289. BMI, body mass index; CRP, C-reactive protein; CV, cardiovascular; FIL100/200, filgotinib 100 mg/200 mg; SD, standard deviation. Acknowledgements We thank the physicians and patients who participated in the studies. The studies were funded by Gilead Sciences (Foster City, CA, United States) and Galapagos NV (Mechelen, Belgium). Publication coordination was provided by Fabien Debailleul, PhD, of Galapagos NV. Writing support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and was funded by Galapagos NV. Disclosure of Interests Xavier Mariette Consultant of: AstraZeneca, BMS, Galapagos, GSK, Novartis, Pfizer, Sven Borchmann Shareholder of: Liqomics, Consultant of: Galapagos, Sandrine Aspeslagh Speakers bureau: AstraZeneca, BMS, Pfizer, Roche, Sanofi, Grant/research support from: AstraZeneca, BMS, Merck, MSD, Pfizer, Roche, Sanofi, Jaime Calvo Speakers bureau: GSK, Galapagos, Novartis, Biogen, Lilly, Paid instructor for: GSK, Consultant of: GSK, AstraZeneca, AbbVie, Sanofi, Novartis, Lilly, Grant/research support from: Roche, BMS, Richard Moriggl Consultant of: Galapagos, Zoltan Szekanecz Speakers bureau: Pfizer, AbbVie, Roche, Lilly, Novartis, Galapagos, Sobi, Gedeon Richter, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis, Galapagos, Sobi, Gedeon Richter, Grant/research support from: Pfizer, Francesco De Leonardis Employee of: Galapagos, Nadia Verbruggen Shareholder of: Galapagos, Employee of: Galapagos, Paul Van Hoek Consultant of: Galapagos, Aspen, AOP Health, Sanofi-Genzyme, Astellas, Employee of: Schering Plough, MSD, Janssen, Marc Schmalzing Speakers bureau: Novartis, AbbVie, AstraZeneca, Chugai/Roche, Janssen-Cilag, Gilead, Boehringer Ingelheim, Mylan, Galapagos, EUSA-Pharma, Consultant of: Chugai/Roche, Hexal/Sandoz, Gilead, AbbVie, Janssen-Cilag, Boehringer Ingelheim, onkowissen.de, EUSA-Pharma, Novartis, AstraZeneca, Amgen, medac, Lilly, Galapagos, UCB, Grant/research support from: Chugai/Roche, Boehringer Ingelheim, Celgene, Medac, UCB, Mylan, Galapagos, Andreas Stallmach Speakers bureau: AbbVie, BMS, Celltrion, CLS Behring, De Prom, Falk Foundation, Ferring, Janssen, Kompetenznetz Darmerkrankungen, MedUpdate, MSD, Recordati Pharma, Sobi, Takeda, Consultant of: AbbVie, Amgen, BMS, Consal, Galapagos, Gilead, Janssen, Lilly, MSD, Repha GmbH, Roche, Pfizer, Pharmacosmos GmbH, Takeda, Tillotts Pharma, Christina Charles-Schoeman Consultant of: Priovant, AbbVie, BMS, Pfizer, Grant/research support from: AbbVie, BMS, Pfizer, CSL Behring, Vijay Rajendran Shareholder of: Galapagos, Employee of: Galapagos, Christine Rudolph Shareholder of: Galapagos, Employee of: Galapagos, Chris Watson Shareholder of: Galapagos, Employee of: Galapagos, Yoshiya Tanaka Speakers bureau: Boehringer Ingelheim, Eli Lilly, AbbVie, Gilead, AstraZeneca, BMS, Chugai, Daiichi-Sankyo, Eisai, Pfizer, Mitsubishi-Tanabe, GlaxoSmithKline, Grant/research support from: Asahi-Kasei, AbbVie, Chugai, Eisai, Takeda, Daiichi-Sankyo, Boehringer Ingelheim, Ernest Choy Speakers bureau: AbbVie, Amgen, BMS, Chugai Pharma, Eli Lilly, Fresenius Kai, Galapagos, Gilead, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis, Consultant of: AbbVie, Amgen, Biogen, Therapeutics, Chugai Pharma, Eli Lilly, Fresenius Kai, Galapagos, Gilead, GSK, Janssen, Novartis, Roche, R-Pharm, SynAct Pharma, Sanofi-Genzyme, UCB, Grant/research support from: Bio-Cancer, Biogen, Novartis, Pfizer, Roche, Sanofi.