Long-Term Safety, Efficacy, and Patient-Centered Outcomes of Filgotinib in the Treatment of Rheumatoid Arthritis: Current Perspectives

References

• Almutairi K, Nossent J, Preen D, Keen H, Inderjeeth C. The global prevalence of rheumatoid arthritis: a meta-analysis based on a systematic review. Rheumatol Int. 2021;41(5):863–877. doi:10.1007/s00296-020-04731-0
   PubMed Web of Science ®Google Scholar
• Almutairi KB, Nossent JC, Preen DB, Keen HI, Inderjeeth CA. The prevalence of rheumatoid arthritis: a systematic review of population-based studies. J Rheumatol. 2021;48(5):669–676. doi:10.3899/jrheum.200367
   PubMed Web of Science ®Google Scholar
• Biggioggero M, Becciolini A, Crotti C, Agape E, Favalli EG. Upadacitinib and filgotinib: the role of JAK1 selective inhibition in the treatment of rheumatoid arthritis. Drugs Context. 2019;8:212595. doi:10.7573/dic.212595
   PubMedGoogle Scholar
• Tanaka Y, Kavanaugh A, Wicklund J, McInnes IB. Filgotinib, a novel JAK1-preferential inhibitor for the treatment of rheumatoid arthritis: an overview from clinical trials. Mod Rheumatol. 2022;32(1):1–11. doi:10.1080/14397595.2021.1902617
   PubMed Web of Science ®Google Scholar
• Tanaka Y, Luo Y, O’Shea JJ, Nakayamada S. Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach. Nat Rev Rheumatol. 2022;18(3):133–145. doi:10.1038/s41584-021-00726-8
   PubMed Web of Science ®Google Scholar
• Angelini J, Talotta R, Roncato R, et al. JAK-inhibitors for the treatment of rheumatoid arthritis: a focus on the present and an outlook on the future. Biomolecules. 2020;10(7):1002. doi:10.3390/biom10071002
   PubMed Web of Science ®Google Scholar
• O’Shea JJ, Kontzias A, Yamaoka K, Tanaka Y, Laurence A. Janus kinase inhibitors in autoimmune diseases. Ann Rheum Dis. 2013;72(suppl 2):ii111–ii115. doi:10.1136/annrheumdis-2012-202576
   PubMed Web of Science ®Google Scholar
• Scherer HU, Haupl T, Burmester GR. The etiology of rheumatoid arthritis. J Autoimmun. 2020;110:102400. doi:10.1016/j.jaut.2019.102400
   PubMed Web of Science ®Google Scholar
• Smolen JS, Landewe RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3–18. doi:10.1136/ard-2022-223356
   PubMed Web of Science ®Google Scholar
• Tanaka Y, Maeshima K, Yamaoka K. In vitro and in vivo analysis of a JAK inhibitor in rheumatoid arthritis. Ann Rheum Dis. 2012;71(suppl 2):i70–i74. doi:10.1136/annrheumdis-2011-200595
   PubMed Web of Science ®Google Scholar
• Kim ES, Keam SJ. Filgotinib in rheumatoid arthritis: a profile of its use. Clin Drug Investig. 2021;41(8):741–749. doi:10.1007/s40261-021-01055-0
   PubMed Web of Science ®Google Scholar
• Combe B, Kivitz A, Tanaka Y, et al. Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial. Ann Rheum Dis. 2021;80(7):848–858. doi:10.1136/annrheumdis-2020-219214
   PubMed Web of Science ®Google Scholar
• Combe BG, Tanaka Y, Buch MH, et al. Efficacy and safety of filgotinib in patients with high risk of poor prognosis who showed inadequate response to MTX: a post hoc analysis of the FINCH 1 study. Rheumatol Ther. 2022;10(1):53–70. doi:10.1007/s40744-022-00498-x
   PubMed Web of Science ®Google Scholar
• Genovese MC, Kalunian K, Gottenberg JE, et al. Effect of filgotinib vs placebo on clinical response in patients with moderate to severe rheumatoid arthritis refractory to disease-modifying antirheumatic drug therapy: the FINCH 2 randomized clinical trial. JAMA. 2019;322(4):315–325. doi:10.1001/jama.2019.9055
   PubMed Web of Science ®Google Scholar
• Kavanaugh A, Kremer J, Ponce L, et al. Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2). Ann Rheum Dis. 2017;76(6):1009–1019. doi:10.1136/annrheumdis-2016-210105
   PubMed Web of Science ®Google Scholar
• Kavanaugh A, Westhovens RR, Winthrop KL, et al. Safety and efficacy of filgotinib: up to 4-year results from an open-label extension study of phase II rheumatoid arthritis programs. J Rheumatol. 2021;48(8):1230–1238. doi:10.3899/jrheum.201183
   PubMed Web of Science ®Google Scholar
• Westhovens R, Rigby WFC, van der Heijde D, et al. Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monotherapy in patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: the phase 3, randomised controlled FINCH 3 trial. Ann Rheum Dis. 2021;80(6):727–738. doi:10.1136/annrheumdis-2020-219213
   PubMed Web of Science ®Google Scholar
• Westhovens R, Taylor PC, Alten R, et al. Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1). Ann Rheum Dis. 2017;76(6):998–1008. doi:10.1136/annrheumdis-2016-210104
   PubMed Web of Science ®Google Scholar
• Winthrop KL, Tanaka Y, Takeuchi T, et al. Integrated safety analysis of filgotinib in patients with moderately to severely active rheumatoid arthritis receiving treatment over a median of 1.6 years. Ann Rheum Dis. 2022;81(2):184–192. doi:10.1136/annrheumdis-2021-221051
   PubMed Web of Science ®Google Scholar
• Tanaka Y, Matsubara T, Atsumi T, et al. Safety and efficacy of filgotinib for Japanese patients with RA and inadequate response to MTX: FINCH 1 52-week results and FINCH 4 48-week results. Mod Rheumatol. 2022:roac084. doi:10.1093/mr/roac084
   Web of Science ®Google Scholar
• Atsumi T, Tanaka Y, Matsubara T, et al. Long-term safety and efficacy of filgotinib treatment for rheumatoid arthritis in Japanese patients naive to MTX treatment (FINCH 3). Mod Rheumatol. 2022:roac083. doi:10.1093/mr/roac083
   Google Scholar
• European Medicines Agency. Jyseleca summary of product characteristics [Annex 1]. European Union: European Medicines Agency; 2022.
   Google Scholar
• Galapagos NV. Long-term follow-up study of GLPG0634 in active rheumatoid arthritis patients (DARWIN 3). NLM identifier: NCT02065700. Available from: https://clinicaltrials.gov/ct2/show/NCT02065700. Accessed February 10, 2023.
   Google Scholar
• Galapagos NV. Long-term extension study to assess the safety and efficacy of filgotinib in adults with rheumatoid arthritis (FINCH 4). NLM identifier: NCT03025308. Available from: https://clinicaltrials.gov/ct2/show/NCT03025308. Accessed February 10, 2023.
   Google Scholar
• Galapagos NV. Dose-finding study of GLPG0634 as monotherapy in active rheumatoid arthritis (RA) participants (DARWIN2). NLM identifier: NCT01894516. Available from: https://clinicaltrials.gov/ct2/show/results/NCT01894516?term=DARWIN+2&draw=2&rank=1&view=results. Accessed March 8, 2023.
   Google Scholar
• Galapagos NV. Dose-finding study of GLPG0634 as add-on to methotrexate in active rheumatoid arthritis participants (DARWIN1). NLM identifier: NCT01888874. Available from: https://clinicaltrials.gov/ct2/show/results/NCT01888874. Accessed March 8, 2023.
   Google Scholar
• Gilead Sciences, Inc. Filgotinib versus placebo in adults with active rheumatoid arthritis (RA) who have an inadequate response to biologic disease-modifying anti-rheumatic drug(s) (DMARDs) treatment (FINCH 2). NLM identifier: NCT02873936. Available from: https://clinicaltrials.gov/ct2/show/results/NCT02873936?term=Finch+2&draw=2&rank=1&view=results. Accessed March 8, 2023.
   Google Scholar
• Gilead Sciences, Inc. Filgotinib alone and in combination with methotrexate (MTX) in adults with moderately to severely active rheumatoid arthritis who are naive to MTX therapy (FINCH 3). NLM identifier: NCT02886728. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT02886728. Accessed March 8, 2023.
   Google Scholar
• Gilead Sciences, Inc. Filgotinib in combination with methotrexate in adults with moderately to severely active rheumatoid arthritis who have an inadequate response to methotrexate (FINCH 1). NLM identifier: NCT02889796. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT02889796. Accessed March 8, 2023.
   Google Scholar
• Jyseleca. Medicines and healthcare products regulatory agency; 2022. Available from: https://products.mhra.gov.uk/search/?search=Jyseleca&page=1. Accessed March 8, 2023.
   Google Scholar
• Anderson K, Zheng H, Kotecha M, et al. The relative bioavailability and effects of food and acid-reducing agents on filgotinib tablets in healthy subjects. Clin Pharmacol Drug Dev. 2019;8(5):585–594. doi:10.1002/cpdd.659
   PubMed Web of Science ®Google Scholar
• Dhillon S, Keam SJ. Filgotinib: first approval. Drugs. 2020;80(18):1987–1997. doi:10.1007/s40265-020-01439-0
   PubMed Web of Science ®Google Scholar
• Buch M, Takeuchi T, Rajendran V, et al. Clinical outcomes up to week 48 of ongoing filgotinib RA long-term extension trial of biologic DMARD inadequate responders initially on filgotinib or placebo in a phase 3 trial. Arthritis Rheumatol. 2021;73(suppl 9):1.
   Google Scholar
• Combe B, Tanaka Y, Emery P, et al. Clinical outcomes up to week 48 of filgotinib treatment in an ongoing long-term extension trial of RA patients with inadequate response to MTX initially treated with filgotinib or adalimumab during the phase 3 parent trial. Arthritis Rheumatol. 2021;73(suppl 9):1.
   Google Scholar
• Aletaha D, Westhovens R, Atsumi T, et al. Clinical outcomes of MTX-naïve RA patients on filgotinib long-term extension trial initially on FIL or MTX during phase 3 parent trial. Arthritis Rheumatol. 2021;73(suppl 9):1.
   Google Scholar
• Winthrop K, Tanaka Y, Takeuchi T, et al. Integrated safety analysis update for filgotinib in patients with moderately to severely active rheumatoid arthritis receiving treatment over a median of 2.2 years. Poster presented at: American College of Rheumatology Annual Meeting; 2021.
   Google Scholar
• Sunzini F, McInnes I, Siebert S. JAK inhibitors and infections risk: focus on herpes zoster. Ther Adv Musculoskelet Dis. 2020;12:1759720X20936059. doi:10.1177/1759720X20936059
   PubMed Web of Science ®Google Scholar
• Gouverneur A, Avouac J, Prati C, et al. POS0225 Risk of major cardiovascular event across JAK inhibitor treated patients: analysis of a national claim database. Ann Rheum Dis. 2021;80(suppl 1):331–332. doi:10.1136/annrheumdis-2021-eular.2976
   Google Scholar
• Burmester GR, Kremer JM, Van den Bosch F, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10139):2503–2512. doi:10.1016/S0140-6736(18)31115-2
   PubMed Web of Science ®Google Scholar
• Genovese MC, Fleischmann R, Combe B, et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial. Lancet. 2018;391(10139):2513–2524. doi:10.1016/S0140-6736(18)31116-4
   PubMed Web of Science ®Google Scholar
• Chodara AM, Wattiaux A, Bartels CM. Managing cardiovascular disease risk in rheumatoid arthritis: clinical updates and three strategic approaches. Curr Rheumatol Rep. 2017;19(4):16. doi:10.1007/s11926-017-0643-y
   PubMed Web of Science ®Google Scholar
• Aubry MC, Maradit-Kremers H, Reinalda MS, Crowson CS, Edwards WD, Gabriel SE. Differences in atherosclerotic coronary heart disease between subjects with and without rheumatoid arthritis. J Rheumatol. 2007;34(5):937–942.
   PubMed Web of Science ®Google Scholar
• Avalos I, Chung CP, Oeser A, et al. Increased augmentation index in rheumatoid arthritis and its relationship to coronary artery atherosclerosis. J Rheumatol. 2007;34(12):2388–2394.
   PubMed Web of Science ®Google Scholar
• Castañeda S, Nurmohamed MT, González-Gay MA. Cardiovascular disease in inflammatory rheumatic diseases. Best Pract Res Clin Rheumatol. 2016;30(5):851–869. doi:10.1016/j.berh.2016.10.006
   PubMed Web of Science ®Google Scholar
• Charles-Schoeman C, Lee YY, Grijalva V, et al. Cholesterol efflux by high density lipoproteins is impaired in patients with active rheumatoid arthritis. Ann Rheum Dis. 2012;71(7):1157–1162. doi:10.1136/annrheumdis-2011-200493
   PubMed Web of Science ®Google Scholar
• Charles-Schoeman C, Watanabe J, Lee YY, et al. Abnormal function of high-density lipoprotein is associated with poor disease control and an altered protein cargo in rheumatoid arthritis. Arthritis Rheum. 2009;60(10):2870–2879. doi:10.1002/art.24802
   PubMedGoogle Scholar
• Libby P. Inflammation in atherosclerosis. Nature. 2002;420(6917):868–874. doi:10.1038/nature01323
   PubMed Web of Science ®Google Scholar
• Wallberg-Jonsson S, Caidahl K, Klintland N, Nyberg G, Rantapaa-Dahlqvist S. Increased arterial stiffness and indication of endothelial dysfunction in long-standing rheumatoid arthritis. Scand J Rheumatol. 2008;37(1):1–5. doi:10.1080/03009740701633238
   PubMed Web of Science ®Google Scholar
• Watanabe J, Charles-Schoeman C, Miao Y, et al. Proteomic profiling following immunoaffinity capture of high-density lipoprotein: association of acute-phase proteins and complement factors with proinflammatory high-density lipoprotein in rheumatoid arthritis. Arthritis Rheum. 2012;64(6):1828–1837. doi:10.1002/art.34363
   PubMed Web of Science ®Google Scholar
• Redeker I, Albrecht K, Kekow J, et al. Risk of herpes zoster (shingles) in patients with rheumatoid arthritis under biologic, targeted synthetic and conventional synthetic DMARD treatment: data from the German RABBIT register. Ann Rheum Dis. 2022;81(1):41–47. doi:10.1136/annrheumdis-2021-220651
   PubMed Web of Science ®Google Scholar
• Cohen SB, Tanaka Y, Mariette X, et al. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017;76(7):1253–1262. doi:10.1136/annrheumdis-2016-210457
   PubMed Web of Science ®Google Scholar
• Cohen SB, Tanaka Y, Mariette X, et al. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open. 2020;6(3):e001395. doi:10.1136/rmdopen-2020-001395
   PubMed Web of Science ®Google Scholar
• Cohen SB, van Vollenhoven RF, Winthrop KL, et al. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis. 2021;80(3):304–311. doi:10.1136/annrheumdis-2020-218510
   PubMed Web of Science ®Google Scholar
• Winthrop KL, Harigai M, Genovese MC, et al. Infections in baricitinib clinical trials for patients with active rheumatoid arthritis. Ann Rheum Dis. 2020;79(10):1290–1297. doi:10.1136/annrheumdis-2019-216852
   PubMed Web of Science ®Google Scholar
• Harrington R, Al Nokhatha SA, Conway R. JAK inhibitors in rheumatoid arthritis: an evidence-based review on the emerging clinical data. J Inflamm Res. 2020;13:519–531. doi:10.2147/JIR.S219586
   PubMed Web of Science ®Google Scholar
• Felson DT, Anderson JJ, Boers M, et al. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995;38(6):727–735. doi:10.1002/art.1780380602
   PubMed Web of Science ®Google Scholar
• Tóth L, Juhász MF, Szabó L, et al. Janus kinase inhibitors improve disease activity and patient-reported outcomes in rheumatoid arthritis: a systematic review and meta-analysis of 24,135 patients. Int J Mol Sci. 2022;23(3). doi:10.3390/ijms23031246
   Web of Science ®Google Scholar
• Aletaha D, Westhovens R, Combe B, et al. POS0676 Efficacy and safety of filgotinib in patients aged greater than 75 years: a post hoc subgroup analysis of the FINCH 4 long-term extension (LTE) study. Ann Rheum Dis. 2022;81(1):612–613. doi:10.1136/annrheumdis-2022-eular.1563
   Google Scholar
• Bingham CO, Walker D, Nash P, et al. The impact of filgotinib on patient-reported outcomes and health-related quality of life for patients with active rheumatoid arthritis: a post hoc analysis of phase 3 studies. Arthritis Res Ther. 2022;24(1):11. doi:10.1186/s13075-021-02677-7
   PubMedGoogle Scholar
• Genovese M, Westhovens R, Meuleners L, et al. Effect of filgotinib, a selective JAK 1 inhibitor, with and without methotrexate in patients with rheumatoid arthritis: patient-reported outcomes. Arthritis Res Ther. 2018;20(1):57. doi:10.1186/s13075-018-1541-z
   PubMed Web of Science ®Google Scholar
• Taylor PC, Fautrel B, Piette Y, et al. Treat-to-target in rheumatoid arthritis: a real-world study of the application and impact of treat-to-target within the wider context of patient management, patient centricity and advanced therapy use in Europe. RMD Open. 2022;8(2):e002658. doi:10.1136/rmdopen-2022-002658
   PubMed Web of Science ®Google Scholar
• Taylor P, Fautrel B, Piette Y, et al. Physicians’ reasons for prescribing Janus kinase inhibitors (JAKi) in patients with rheumatoid arthritis, and associated alignment between physicians and patients in a real-world clinical setting. Arthritis Rheumatol. 2021;73(suppl 9):1.
   Google Scholar
• Traves PG, Murray B, Campigotto F, Galien R, Meng A, Di Paolo JA. JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib. Ann Rheum Dis. 2021;80(7):865–875. doi:10.1136/annrheumdis-2020-219012
   PubMed Web of Science ®Google Scholar
• Food and Drug Administration. Gilead receives complete response letter for filgotinib for the treatment of moderately to severely active rheumatoid arthritis; 2020. Available from: https://wwwam10.gilead.com/en/news-and-press/press-room/press-releases/2020/8/gilead-receives-complete-response-letter-for-filgotinib-for-The-treatment-of-moderately-to-severely-active-rheumatoid-arthritis. Accessed February 17, 2023.
   Google Scholar
• Hellstrom WJG, Dolhain R, Ritter TE, et al. MANTA and MANTA-RAy: rationale and design of trials evaluating effects of filgotinib on semen parameters in patients with inflammatory diseases. Adv Ther. 2022;39(7):3403–3422. doi:10.1007/s12325-022-02168-4
   PubMed Web of Science ®Google Scholar
• Galapagos NV. Prospective observational study of filgotinib in subjects with rheumatoid arthritis (FILOSOPHY). NLM identifier: NCT04871919. Available from: https://clinicaltrials.gov/ct2/show/NCT04871919. Accessed February 17, 2023.
   Google Scholar
• Galapagos NV. Prospective observational study of filgotinib in female participants with rheumatoid arthritis in France (PARROTFISH). NLM identifier: NCT05323591. Available from: https://www.clinicaltrials.gov/ct2/show/NCT05323591?term=filgotinib&cond=rheumatoid+arthritis&draw=2&rank=1. Accessed February 17, 2023.
   Google Scholar