2,319
Views
44
CrossRef citations to date
0
Altmetric
Review

Upadacitinib for the treatment of rheumatoid arthritis

&
Pages 13-25 | Received 25 Jul 2018, Accepted 02 Nov 2018, Published online: 19 Nov 2018

References

  • Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388:2023–2038.
  • Cojocaru M, Cojocaru IM, Silosi I, et al. Extra-articular manifestations in rheumatoid arthritis. Maedica. 2010;5:286–291.
  • Smolen JS, Aletaha D, Barton A, et al. Rheumatoid arthritis. Nat Rev Dis Prim. 2018;4.
  • van der Heide A, Jacobs JW, Bijlsma JW, et al. The effectiveness of early treatment with “second-line” antirheumatic drugs: a randomized, controlled trial. Ann Intern Med. 1996;124(8):699–707.
  • Emery P, Solem C, Majer I, et al. A European chart review study on early rheumatoid arthritis treatment patterns, clinical outcomes, and healthcare utilization. Rheumatol Int. 2015;35(11):1837–1849.
  • Smolen JS, Aletaha D. Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges. Nat Rev Rheumatol. 2015;11:276–289.
  • Smolen JS, Landewé J, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017.
  • Singh JA, Saag KG, Bridges SL Jr., et al. 2015 American college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016;68(1):1–26.
  • Yamaoka K. Janus kinase inhibitors for rheumatoid arthritis. Curr Opin Chem Biol. 2016;32:29–33.
  • Banerjee S, Biehl A, Gadina M, et al. JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs. 2017;77(5):521–546.
  • Nakayamada S, Kubo S, Iwata S, et al. Recent progress in JAK inhibitors for the treatment of Rheumatoid arthritis. BioDrugs. 2016;30(5):407–419.
  • Semerano L, Decker P, Clavel G, et al. Developments with investigational Janus Kinase inhibitors for rheumatoid arthritis. Expert Opin Invest Drugs. 2016;25(12):1355–1359.
  • Perry E, Kelly C, Eggleton P, et al. The lung in ACPA-positive rheumatoid arthritis: an initiating site of injury? Rheumatology (Oxford). 2014;53(11):1940–1950.
  • Derksen VFAM, Huizinga TWJ. The role of autoantibodies in the pathophysiology of rheumatoid arthritis. Semin Immunopathol. 2017;39(4):437–446.
  • Firestein GS, McInnes IB. Immunopathogenesis of Rheumatoid Arthritis. Immunity. 2017;46(2):183–196.
  • Holers VM. Autoimmunity to citrullinated proteins and the initiation of rheumatoid arthritis. Curr Opin Immunol. 2013;25(6):728–735.
  • Muller S, Radic M. Citrullinated autoantigens: from diagnostic markers to pathogenetic mechanisms. Clin Rev Allerg Immunol. 2015;42(2):232–239.
  • Laurent L, Clavel C, Lemaire O, et al. Fcγ receptor profile of monocytes and macrophages from rheumatoid arthritis patients and their response to immune complexes formed with autoantibodies to citrullinated proteins. Ann Rheum Dis. 2011;70(6):1052–1059.
  • Pratesi F, Dioni I, Tommasi C. Antibodies from patients with rheumatoid arthritis target citrullinated histone 4 contained in neutrophils extracellular traps. Ann Rheum Dis. 2014;73(7):1414–1422.
  • Arend WP, Firestein GS. Pre-rheumatoid arthritis: predisposition and transition to clinical synovitis. Nat Rev Rheumatol. 2012;8(10):573–586.
  • Guo Q, Wang Y, Xu D, et al. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res. 2018;6(15).
  • Zhang Y, Wei F, Liu CJ. Overexpression of ADAMTS-7 leads to accelerated initiation and progression of collagen-induced arthritis in mice. Mol Cell Biochem. 2015;404:171–179.
  • Liu CJ. The role of ADAMTS-7 and ADAMTS-12 in the pathogenesis of arthritis. Nat Clin Pract Rheumatol. 2009;5(1):38–45.
  • McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205–2219.
  • Hwang D, Kim WU. Modelling cytokine signalling networks. Nat Rev Rheumatol. 2017;1:5–6.
  • Hammaker D, Sweeney S, Firestein GS. Signal transduction networks in rheumatoid arthritis. Ann Rheum Dis. 2003;62(2):86–89.
  • Kumar S, Boehm J, Lee JC. P38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases. Nature Rev Drug Discov. 2003;2:717–726.
  • Smolen JS, Steiner G. Therapeutic strategies for rheumatoid arthritis. Nature Rev Drug Discov. 2003;2:473–488.
  • O’Shea JJ, Laurence A, McInnes IB. Back to the future: oral targeted therapy for RA and other autoimmune diseases. Nat Rev Rheumatol. 2013;9(3):173–182.
  • Patterson H, Nibbs R, McInnes I, et al. Protein kinase inhibitors in the treatment of inflammatory and autoimmune diseases. Clin Exp Immunol. 2013;176:1–10.
  • Hawkins PT, Stephens LR. PI3K signalling in inflammation. Biochim Biophys Acta. 2015;1851:882–897.
  • Rommel C, Camps M, Ji H. PI3Kδ and PI3Kγ: partners in crime in inflammation in rheumatoid arthritis and beyond? Nat Rev Immunol. 2007;7:191–201.
  • Malemud C. The role of the JAK/STAT signal pathway in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2018;10:117–127.
  • Malemud C. Intracellular signaling pathways in rheumatoid arthritis. J Clin Cell Immunol. 2013;4:160.
  • Mori T, Miyamoto T, Yoshida H, et al. IL-1β and TNFα-initiated IL-6-STAT3 pathway is critical in mediating inflammatory cytokines and RANKL expression in inflammatory arthritis. Int Immunol. 2011;23(11):701–712.
  • Farlik M, Reutterer B, Schindler C, et al. Nonconventional initiation complex assembly by STAT and NF-κB transcription factors regulates nitric oxide synthase expression. Immunity. 2010;33(1):25–34.
  • Yang XO, Panopoulos AD, Nurieva R, et al. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem. 2007;282(13):9358–9363.
  • Schwartz DM, Kanno Y, Villarino A, et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;16(12):843–862.
  • Walker JG, Ahern MJ, Coleman M, et al. Expression of Jak3, STAT1, STAT4, and STAT6 in inflammatory arthritis: unique Jak3 and STAT4 expression in dendritic cells in seropositive rheumatoid arthritis. Ann Rheum Dis. 2006;65(2):149–156.
  • Walker JG, Ahern MJ, Coleman M, et al. Changes in synovial tissue Jak-STAT expression in rheumatoid arthritis in response to successful DMARD treatment1. Ann Rheum Dis. 2006;65(2):558–1564.
  • Schwartz D, Bonelli M, Gadina M, et al. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat Rev Rheumatol. 2016;12(1):1558–1562.
  • Leonard WJ, O’Shea JJ. JAKs and STATs: biological implications. Ann Rev Immunol. 1998;16:293–322.
  • Villarino AV, Kanno Y, O’Shea JJ. Mechanisms and consequences of JAK-STAT signaling in the immune system. Nat Immunol. 2017;18(4):374–484.
  • Mascarenhas J, Hoffman R. Ruxolitinib: the first FDA approved therapy for the treatment of myelofibrosis. Clin Cancer Res. 2012;18(11):3008–3014.
  • van der Heijde D, Tanaka Y, Fleischmann R, et al. Tofacitinib (CP-690,550) in patients with rheumatoid arthritis receiving methotrexate twelve-month data from a twenty-four–month phase III randomized radiographic study. Arthritis Rheumatism. 2013;65(3):559–570.
  • Cosgrove SB, Wren JA, Cleaver DM, et al. A blinded, randomized, placebo-controlled trial of the efficacy and safety of the Janus kinase inhibitor oclacitinib (Apoquel®) in client-owned dogs with atopic dermatitis. Vet Dermatol. 2013;24(6):587–597.
  • Wollenhaupt J, Silverfield J, Lee EB, et al. Tofacitinib, an oral Janus kinase inhibitor, in the treatment of rheumatoid arthritis: safety and efficacy in open-label, long-term extension studies over 9 years. Arthritis Rheumatol. 2017;69(10):Abstract 522.
  • Lee EB, Fleischmann R, Hall S, et al. Tofacitinib versus methotrexate in rheumatoid arthritis. N Engl J Med. 2014;370(25):2377–2386.
  • Vollenhoven RF, Fleischmann R, Cohen S, et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med. 2012;367(6):508–519.
  • Fleischmann R, Kremer J, Cush J, et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med. 2012;367(6):495–507.
  • Kremer K, Hall ZG, Li S, et al. Tofacitinib in combination with nonbiologic disease- modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2013;159(4):253–261.
  • Burmester GR, Blanco R, Charles-Schoeman C, et al. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Lancet. 2013;381(9865):451–460.
  • Fleischmann R, Schiff M, van der Heijde D, et al. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arhritis Rheumatol. 2017;69(3):506–517.
  • Taylor P, Keystone E, van der Heijde D, et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med. 2017;376(7):652–662.
  • Dougados M, van der Heijde D, Chen Y, et al. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study. Clin Epidemiol Res. 2017;76(1):88–95.
  • Genovese M, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374(13):1243–1252.
  • 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 Rheumatic Dis. 2017;76:998–1008.
  • 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 Rheumatic Dis. 2017;76:1009–1019.
  • 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(10066):266–275.
  • D’Amico F, Fiorino G, Furfaro F, et al. Janus kinase inhibitors for the treatment of inflammatory bowel diseases: developments from phase I and phase II clinical trials. Expert Opin Invest Drugs. 2018;27(7):595–599.
  • Genovese MC, Yang F, Østergaard M, et al. 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(11):1979–1983.
  • Genovese MC, van Vollenhoven RF, Pacheco-Tena C, et al. VX-509 (Decernotinib), an oral selective JAK-3 inhibitor, in combination with methotrexate in patients with rheumatoid arthritis. Arthritis Rheumatol. 2016;68(1):46–55.
  • Telliez JB, Dowty ME, Wang L, et al. Discovery of a JAK3-selective inhibitor: functional differentiation of JAK3-selective inhibition over pan-JAK or JAK1-selective inhibition. ACS Chem Biol. 2016;11(12):3442–3451.
  • Voss J, Graff C, Schwartz A, et al. Pharmacodynamics of a novel JAK1 selective inhibitors in rat arthritis and anemia models and in helathy human subjects [Abstract]. Ann Rheum Dis. 2014;73(2):222.
  • Moy LY, Chiu CS, Faltus R, et al. Efficay of a novel orally bioavailable JAK1 selective compound in a preclinical rat collagen-induced arthritis model [Abstract number 2354]. In: ACR/ARHP annual meeting. 2014. Rheumatoid Arthritis - Animal Models. Available from: https://acrabstracts.org
  • Clinicaltrials.gov. A study comparing ABT-494 to placebo and to adalimumab in participants with psoriatic arthritis who have an inadequate response to at least one non-biologic disease modifying anti-rheumatic drug (SELECT - PsA 1). NCT03104400, 2017.
  • Clinicaltrials.gov. A study comparing ABT-494 to placebo in participants with active psoriatic arthritis who have a history of inadequate response to at least one biologic disease modifying anti-rheumatic drug (SELECT - PsA 2). NCT03104374, 2017.
  • ClinicalTrials.gov. A multicenter, randomized, double-blind, placebo-controlled study of ABT-494 for the induction of symptomatic and endoscopic remission in subjects with moderately to severely active Crohn’s disease who have inadequately responded to or are intolerant to I. NCT02365649.
  • Clinicaltrials.gov. A study to evaluate the safety and efficacy of ABT-494 for induction and maintenance therapy in subjects with moderately to severely active ulcerative colitis. NCT02819635, 2017.
  • Clinicaltrials.gov. A study to evaluate ABT-494 in adult subjects with moderate to severe atopic dermatitis. NCT02925117, 2017.
  • Mohamed MF, Camp HS, Jiang P, et al. Pharmacokinetics, safety and tolerability of ABT-494, a novel selective JAK1 inhibitor, in healthy volunteers and subjects with rheumatoid arthritis. Clin Pharmacokinet. 2016;55(12):1547–1558.
  • Klunder B, Mohamed MF, Othman AA. Population pharmacokinetics of upadacitinib in healthy subjects and subjects with rheumatoid arthritis: analyses of phase I and II clinical trials. Clin Pharmacokinet. 2018;57(8):977–988.
  • Kremer JM, Emery P, Camp HS, et al. Phase IIB study of ABT-494, a selective JAK-1 inhibitor, in patients with rheumatoid arthritis and an inadequate response to anti-tumor necrosis factor therapy. Arthritis Rheumatol. 2016;68(12):2867–2877.
  • 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 inadequate response to methotrexate. Arthritis Rheumatol. 2016;68(12):2857–2866.
  • Mohamed MEF, Coppola S, Feng T, et al. Characterisation of the effect of renal impairement on Upadacitinib pharamcokinetics [Abstract]. Ann Rheum Dis. 2018;77(2):1400–1401.
  • Mohamed MEF, Coppola S, Feng T, et al. Mild and moderate hepatic impairement have no clinically relevant impact on Upadacitinib pharmacokinetics: results from a dedicated phase I study [Abstract]. Ann Rheum Dis. 2018;77(2):1400.
  • Mohamed ME, Jungerwirth S, Asatryan A, et al. Assessment of the effect of CYP3A inhibition, CYP induction, OATP1B inhibition and administration of high-fat meal on the pharmacokinetics of the potent and selective JAK1 inhibitor ABT-494 [Abstract]. Br J Clin Pharmacol. 2017;83(10):2242–2248.
  • Mohamed MEF, Trueman S, Feng T, et al. The selective JAK1 inhibitor upadacitinib has no effect on pharmacokinetics of the hormonal contraceptives levonorgestrel and ethinylestradiol [Abstract number 506]. Arthritis Rheumatol. 2017;69(10).
  • Genovese MC, Kremer J, Zhong S, et al. Long-term safety and efficacy of upadacitinib (ABT-494), an oral JAK-1 inhibitor in patients with rheumatoid arthritis in an open label extension study [Abstract]. Ann Rheumatic Dis. 2017;69(10):979.
  • Klunder B, Mohamed MEF, Camp HS, et al. Exposure-response analysis of the effect of upadacitinib on ACR responses in the phase 2b rheumatoid arthritis trials in patients with inadequate response to methotrexate or to anti-tumor necrosis factor therapy [Abstract number 505]. Arthritis Rheumatol. 2017;69(10).
  • Burmester GR, Kremer JM, Den Bosch V, 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.
  • Genovese MC, Fleishmann 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.
  • Van Vollenhoven R, Dore R, Chen K, et al. Impact of 12 weeks of upadacitinib treatment on individual and composite disease measures in patiens with rheumatoid arthritis and inadequate response to conventional synthetic and biologic dmards. Ann Rheumatic Dis. 2018;77(2):A984.
  • Smolen JS, Cohen S, Emery P, et al. Upadacitinib as monotherapy: a phase 3 randomised controlled double-blind study in patients with active rheumatoid arthritis and inadequate response to methotrexate [Abstract]. Ann Rheum Dis. 2018;77(2):A67.
  • Van Vollenhoven R, Takeuchi T, Pangan AL, et al. A phase 3, randomized, controlled trial comparing upadacitinib monotherapy to MTX monotherapy in MTX-Naïve patients with active rheumatoid arthritis [Abstract number 891]. Arthtitis Rheumatol. 2018;70(10,).
  • Fleischmann R, Pangan AL, Mysler E, et al. A phase 3, randomized, double-blind study comparing upadacitinib to placebo and to adalimumab, in patients with active rheumatoid arthritis with inadequate response to methotrexate [Abstract number 890]. Arthritis Rheumatol. 2018;70(10).
  • Clincaltrials.gov. [cited 2018 Oct 15]. A phase 3 study to compare upadacitinib to abatacept in subjects with rheumatoid arthritis on stable dose of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) who have inadequate response or intolerance to biologic DMARDs SELECT-CHOICE. NCT03086343, 2018.
  • McInnes IB, Higgs R, Lee J, et al. Ex vivo comparison of baricitinib, upadacitinib, filgotinib and tofacitinib for cytokine signalling in human leucocyte subpopulations [Abstract]. Ann Rheum Dis. 2018;77(1).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.