Clinical efficacy of new JAK inhibitors under development. Just more of the same?

Rheumatology (United Kingdom)

Volumn 58, Issue , 2019, Pages i27-i33

  Westhovens, Rene ^a  

^a UNIVERSITY HOSPITALS LEUVEN   (Belgium)

Author keywords

decernotinib; filgotinib; Janus kinase inhibitor; peficitinib; RA; upadacitinib

Indexed keywords

DECERNOTINIB; FILGOTINIB; JANUS KINASE INHIBITOR; PEFICITINIB; UPADACITINIB; 2-((2-(1H-PYRROLO(2,3-B)PYRIDIN-3-YL)PYRIMIDIN-4-YL)AMINO)-2-METHYL-N-(2,2,2-TRIFLUOROETHYL)BUTANAMIDE; ADAMANTANE; AZETIDINE DERIVATIVE; BARICITINIB; FUSED HETEROCYCLIC RINGS; JANUS KINASE 1; JANUS KINASE 3; NICOTINAMIDE; PIPERIDINE DERIVATIVE; PYRIDINE DERIVATIVE; PYRIMIDINE DERIVATIVE; PYRROLE DERIVATIVE; SULFONAMIDE; TOFACITINIB; TRIAZOLE DERIVATIVE; VALINE;

ARTICLE; CLINICAL EFFECTIVENESS; HUMAN; INFLAMMATION; MEDICAL RESEARCH; NONHUMAN; PRIORITY JOURNAL; RHEUMATOID ARTHRITIS; THERAPY EFFECT; TREATMENT OUTCOME;

ADAMANTANE; ARTHRITIS, RHEUMATOID; AZETIDINES; HETEROCYCLIC COMPOUNDS, 2-RING; HETEROCYCLIC COMPOUNDS, 3-RING; HUMANS; JANUS KINASE 1; JANUS KINASE 3; JANUS KINASE INHIBITORS; NIACINAMIDE; PIPERIDINES; PYRIDINES; PYRIMIDINES; PYRROLES; SULFONAMIDES; TREATMENT OUTCOME; TRIAZOLES; VALINE;

EID: 85062190913     PISSN: 14620324     EISSN: 14620332     Source Type: Journal    
DOI: 10.1093/rheumatology/key256     Document Type: Article

References (41)

1. Smolen JS, Landewé R, Bijlsma J. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76:1102-977.
2. Meyfroidt S, Hulscher M, De Cock D et al. A maximum difference scaling survey of barriers to intensive combination treatment strategies with glucocorticoids in early rheumatoid arthritis. Clin Rheumatol 2015;34:861-9.
3. Leon L, Rodriguez-Rodriguez L, Rosales Z et al. Longterm drug survival of biological agents in patients with rheumatoid arthritis in clinical practice. Scand J Rheumatol 2016;45:456-60.
4. Favalli EG, Pregnolato F, Biggioggero M et al. Twelve-year retention rate of first-line tumor necrosis factor inhibitors in rheumatoid arthritis: real-life data from a local registry. Arthritis Care Res (Hoboken) 2016;68:432-9.
5. Westhovens R, Annemans L. Costs of drugs for treatment of rheumatic diseases. RMD Open 2016;2:e000259.
6. Taylor PC. Clinical efficacy of launched JAK inhibitors in rheumatoid arthritis. Rheumatology 2019;58:i17-i26.
7. Van Rompaey L, Galien R, van der Aar EM et al. Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases. J Immunol 2013;191:3568-77.
8. Vanhoutte F, Mazur M, Voloshyn O et al. Efficacy, safety, pharmacokinetics, and pharmacodynamics of filgotinib, a selective JAK-1 inhibitor, after short-term treatment of rheumatoid arthritis: results of two randomized phase IIa trials. Arthritis Rheumatol 2017;69:1949-59.
9. Namour F, Diderichsen PM, Cox E et al. Pharmacokinetics and pharmacokinetic/pharmacodynamic modeling of filgotinib (GLPG0634), a selective JAK1 inhibitor, in support of phase IIB dose selection. Clin Pharmacokinet 2015;54:859-74.
10. 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, dosefinding study (DARWIN 1). Ann Rheum Dis 2017;76:998-1008.
11. 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, dosefinding study (DARWIN 2). Ann Rheum Dis 2017;76:1009-1019.
12. Genovese M, Kavanaugh A, Winthrop K et al. Long term safety of filgotinib in the treatment of rheumatoid arthritis: week 84 data from a phase 2b open-label extension study. Arthritis Rheumatol 2017;69(Suppl 10):Abstract 1909.
13. Voss J, Graff C, Schwartz A et al. Pharmacodynamics of a novel Jak1 selective inhibitor in rat arthritis and anemia models and in healthy human subjects. Ann Rheum Dis 2014;73:222.
14. Mohamed MF, Camp HS, Jiang P et al. Pharmacokinetics, safety and tolerability of ABT-494, a novel selective JAK 1 inhibitor, in healthy volunteers and subjects with rheumatoid arthritis. Clin Pharmacokinet 2016;55:1547-58.
15. Genovese MC, Smolen JS, Weinblatt ME et al. Efficacy and safety of ABT-494, a selective JAK-1 inhibitor, in a phase IIb study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Arthritis Rheumatol 2016;68:2857-66.
16. Kremer JM, Emery P, Camp HS et al. A phase IIb study of ABT-494, a selective JAK-1 inhibitor, in patients with rheumatoid arthritis and an inadequate response to antitumor necrosis factor therapy. Arthritis Rheumatol 2016;68:2867-77.
17. Genovese MC, Kremer J, Zhong S, Friedman A. Longterm safety and efficacy of upadacitinib (ABT-494), an oral JAK-1 inhibitor in patients with rheumatoid arthritis in an open label extension study. Arthritis Rheumatol 2017;69(Suppl 10):Abstract 509.
18. 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, placebocontrolled phase 3 trial. Lancet 2018;391:2503-12.
19. 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;391:2513-24.
20. Ito M, Yamazaki S, Yamagami K et al. A novel JAK inhibitor, peficitinib, demonstrates potent efficacy in a rat adjuvant-induced arthritis model. J Pharmacol Sci 2017;133:25-33.
21. Cao YJ, Sawamoto T, Valluri U et al. Pharmacokinetics, pharmacodynamics, and safety of ASP015K (peficitinib), a new Janus kinase inhibitor, in healthy subjects. Clin Pharmacol Drug Dev 2016;5:435-49.
22. Papp K, Pariser D, Catlin M et al. A phase 2a randomized, double-blind, placebo-controlled, sequential dose-escalation study to evaluate the efficacy and safety of ASP015K, a novel Janus kinase inhibitor, in patients with moderate-to-severe psoriasis. Br J Dermatol 2015;173:767-76.
23. Takeuchi T, Tanaka Y, Iwasaki M et al. Efficacy and safety of the oral Janus kinase inhibitor peficitinib (ASP015K) monotherapy in patients with moderate to severe rheumatoid arthritis in Japan: a 12-week, randomised, double-blind, placebo-controlled phase IIb study. Ann Rheum Dis 2016;75:1057-64.
24. Kivitz AJ, Gutierrez-Ureña SR, Poiley J et al. Peficitinib, a JAK inhibitor, in the treatment of moderate-to-severe rheumatoid arthritis in patients with an inadequate response to methotrexate. Arthritis Rheumatol 2017;69:709-19.
25. Genovese MC, Greenwald M, Codding C et al. Peficitinib, a JAK inhibitor, in combination with limited conventional synthetic disease-modifying antirheumatic drugs in the treatment of moderate-to-severe rheumatoid arthritis. Arthritis Rheumatol 2017;69:932-42.
26. Mahajan S, Hogan JK, Shlyakhter D et al. VX-509 (decernotinib) is a potent and selective Janus kinase 3 inhibitor that attenuates inflammation in animal models of autoimmune disease. J Pharmacol Exp Ther 2015;353:405-14.
27. Fleischmann RM, Damjanov NS, Kivitz AJ et al. A randomized, double-blind, placebo-controlled, twelve-week, dose-ranging study of decernotinib, an oral selective JAK- 3 inhibitor, as monotherapy in patients with active rheumatoid arthritis. Arthritis Rheumatol 2015;67:334-43.
28. Genovese MC, van Vollenhoven RF, Pacheco-Tena C, Zhang Y, Kinnman N. VX-509 (Decernotinib), an oral selective JAK-3 inhibitor, in combination with methotrexate in patients with rheumatoid arthritis. Arthritis Rheumatol 2016;68:46-55.
29. Genovese MC, Yang F, Østergaard M, Kinnman N. Efficacy of VX-509 (decernotinib) in combination with a disease-modifying antirheumatic drug in patients with rheumatoid arthritis: clinical and MRI findings. Ann Rheum Dis 2016;75:1979-83.
30. Gadina M, Schwartz DM, O'Shea JJ. Decernotinib: a nextgeneration Jakinib. Arthritis Rheumatol 2016;68:31-4.
31. Namour F, Desrivot J, Van der Aa A et al. Clinical confirmation that the selective JAK1 inhibitor filgotinib (GLPG0634) has a low liability for drug-drug interactions. Drug Metab Lett 2016;10:38-48.
32. Mohamed MF, Jungerwirth S, Asatryan A, Jiang P, Othman AA. Assessment of effect of CYP3A inhibition, CYP induction, OATP1B inhibition, and high-fat meal on pharmacokinetics of the JAK1 inhibitor upadacitinib. Br J Clin Pharmacol 2017;83:2242-8.
33. McInnes IB, Higgs R, Lee J. Ex vivo comparison of baricitinib, upadacitinib, filgotinib, and tofacitinib for cytokine signaling in human leukocyte subpopulations. Arthritis Rheumatol 2017;69(Suppl 10):Abstract 2870.
34. Han C, Rahman MU, Doyle MK et al. Association of anemia and physical disability among patients with rheumatoid arthritis. J Rheumatol 2007;34:2177-82.
35. Klamerus KJ, Alvey C, Li L et al. Evaluation of the potential interaction between tofacitinib and drugs that undergo renal tubular secretion using metformin, an in vivo marker of renal organic cation transporter 2. Clin Pharmacol Drug Dev 2014;3:499-507.
36. Baker KF, Isaacs JD. Novel therapies for immunemediated inflammatory diseases: what can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn's disease and ulcerative colitis? Ann Rheum Dis 2018;77:175-87.
37. Vermeire S, Schreiber S, Petryka R et al. Clinical remission in patients with moderate-to-severe Crohn's disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial. Lancet 2017;389:266-75.
38. Adis Insight. Find your Insights: make better informed strategic decisions with accurate, interlinked narratives about drug development. http://adisinsight.springer.com (19 January 2018, date last accessed).
39. Sands BE, Sandborn WJ, Feagan BG et al. Peficitinib, an oral Janus kinase inhibitor, in moderate-to-severe ulcerative colitis: results from a randomized, phase 2 study. J Crohns Colitis 2018;10:1158-69.
40. Westhovens R, Yocum D, Han J et al. The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: a large, randomized, placebo-controlled trial. Arthritis Rheum 2006;54:1075-86.
41. Verschueren P, Westhovens R. Optimal care for early RA patients: the challenge of translating scientific data into clinical practice. Rheumatology (Oxford) 2011;50:1194-200.