Skip to main content

Tipp

Weitere Artikel dieser Ausgabe durch Wischen aufrufen

Erschienen in: rheuma plus 6/2020

07.08.2020 | Rheumatologie | tsDMARDs

Januskinase-Inhibitoren

State of the Art im klinischen Einsatz und Zukunftsperspektiven

verfasst von: Prof. Dr. R. Alten, M. Mischkewitz, A.-L. Stefanski, T. Dörner

Erschienen in: rheuma plus | Ausgabe 6/2020

Einloggen, um Zugang zu erhalten
share
TEILEN

Zusammenfassung

Hintergrund

In der Pathogenese von Autoimmunerkrankungen spielen Zytokine und deren intrazelluläre Signalkaskaden eine zentrale Rolle. An dieser intrazellulären Signalübertragung sind auch sog. Januskinasen (JAK) beteiligt. Die zur Gruppe der „targeted synthetic disease-modifying antirheumatic drugs“ (tsDMARDs) zählenden Januskinase-Inhibitoren (JAKi) sind eine relativ junge und vielversprechende Wirkstoffklasse in der Therapie autoimmuner Krankheitsbilder.

Wirksamkeit

Mittlerweile sind für die Behandlung der rheumatoiden Arthritis (RA) drei Wirkstoffe, Tofacitinib, Baricitinib und Upadacitinib, in den USA, der Schweiz und der EU zugelassen. Auch Filgotinib, ein weiterer JAKi, zeigt vielversprechende Ergebnisse in der Therapie der RA. Darüber hinaus wurde Tofacitinib auch für die Therapie der ulzerativen Kolitis und der Psoriasisarthritis zugelassen. Zusätzlich zu den bereits genannten wurden und werden weitere JAKi wie Filgotinib oder Peficitinib in zahlreichen Studien zu Indikationen wie atopische Dermatitis, ankylosierende Spondylitis oder systemischer Lupus erythematodes untersucht.

Sicherheit

Als Immunsuppressiva weisen JAKi eine mit Biologika vergleichbare erhöhte Inzidenz für schwere Infekte auf. Bemerkenswert ist die erhöhte Reaktivierung des Varicella-Zoster-Virus. Auch Zytopenien treten unter JAKi-Therapie überhäufig auf. Klinisch relevant ist hierbei v. a. die beobachtete Lymphopenie, die mit einem erhöhten Auftreten von schweren Infekten assoziiert ist. Ein erhöhtes Risiko besteht weiterhin für thromboembolische Ereignisse, insbesondere Lungenembolien. Die Risiken hinsichtlich metabolischer Veränderungen und des Auftretens maligner Neoplasien sind vergleichbar mit denen unter Biologikatherapie.
Literatur
1.
Zurück zum Zitat Banerjee S et al (2017) JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs 77(5):521–546 PubMedPubMedCentralCrossRef Banerjee S et al (2017) JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs 77(5):521–546 PubMedPubMedCentralCrossRef
2.
Zurück zum Zitat Rodig SJ et al (1998) Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses. Cell 93:373–383 CrossRefPubMed Rodig SJ et al (1998) Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses. Cell 93:373–383 CrossRefPubMed
3.
Zurück zum Zitat Neubauer H et al (1998) Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis. Cell 93:397–409 CrossRefPubMed Neubauer H et al (1998) Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis. Cell 93:397–409 CrossRefPubMed
4.
Zurück zum Zitat Leonard WJ et al (1994) The molecular basis of X‑linked severe combined Immunodeficiency: the role of the Interleukin‑2 receptor γ chain as a common γ chain, γc. Immunol Rev 138(1):61–86 CrossRefPubMed Leonard WJ et al (1994) The molecular basis of X‑linked severe combined Immunodeficiency: the role of the Interleukin‑2 receptor γ chain as a common γ chain, γc. Immunol Rev 138(1):61–86 CrossRefPubMed
5.
Zurück zum Zitat McIntosh LA et al (2017) Genome-wide association meta-analysis reveals novel juvenile idiopathic arthritis susceptibility loci. Arthritis Rheumatol 69(11):2222–2232 PubMedPubMedCentralCrossRef McIntosh LA et al (2017) Genome-wide association meta-analysis reveals novel juvenile idiopathic arthritis susceptibility loci. Arthritis Rheumatol 69(11):2222–2232 PubMedPubMedCentralCrossRef
6.
Zurück zum Zitat Tao J‑H et al (2011) Meta-analysis of TYK2 gene polymorphisms association with susceptibility to autoimmune and inflammatory diseases. Mol Biol Rep 38(7):4663–4672 CrossRefPubMed Tao J‑H et al (2011) Meta-analysis of TYK2 gene polymorphisms association with susceptibility to autoimmune and inflammatory diseases. Mol Biol Rep 38(7):4663–4672 CrossRefPubMed
7.
Zurück zum Zitat Nangalia J, Grinfeld J, Green AR (2016) Pathogenesis of myeloproliferative disorders. Annu Rev Pathol 11(1):101–126 CrossRefPubMed Nangalia J, Grinfeld J, Green AR (2016) Pathogenesis of myeloproliferative disorders. Annu Rev Pathol 11(1):101–126 CrossRefPubMed
8.
Zurück zum Zitat O’Shea JJ, Gadina M (2019) Selective Janus kinase inhibitors come of age. Nat Rev Rheumatol 15(2):74–75 CrossRefPubMed O’Shea JJ, Gadina M (2019) Selective Janus kinase inhibitors come of age. Nat Rev Rheumatol 15(2):74–75 CrossRefPubMed
9.
Zurück zum Zitat Choy EH (2019) Clinical significance of Janus Kinase inhibitor selectivity. Rheumatology 58(6):953–962 CrossRefPubMed Choy EH (2019) Clinical significance of Janus Kinase inhibitor selectivity. Rheumatology 58(6):953–962 CrossRefPubMed
10.
Zurück zum Zitat Fleischmann R et al (2012) Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med 367(6):495–507 CrossRefPubMed Fleischmann R et al (2012) Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N Engl J Med 367(6):495–507 CrossRefPubMed
11.
Zurück zum Zitat Burmester GR et al (2013) 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 381(9865):451–460 CrossRefPubMed Burmester GR et al (2013) 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 381(9865):451–460 CrossRefPubMed
12.
Zurück zum Zitat Kremer J et al (2013) Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann Intern Med 159(4):253–261 CrossRefPubMed Kremer J et al (2013) Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann Intern Med 159(4):253–261 CrossRefPubMed
13.
Zurück zum Zitat van Vollenhoven RF et al (2012) Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med 367(6):508–519 CrossRefPubMed van Vollenhoven RF et al (2012) Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N Engl J Med 367(6):508–519 CrossRefPubMed
14.
Zurück zum Zitat Lee EB et al (2014) Tofacitinib versus methotrexate in rheumatoid arthritis. N Engl J Med 370(25):2377–2386 CrossRefPubMed Lee EB et al (2014) Tofacitinib versus methotrexate in rheumatoid arthritis. N Engl J Med 370(25):2377–2386 CrossRefPubMed
15.
Zurück zum Zitat Fleischmann R et al (2017) Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial. Lancet 390(10093):457–468 CrossRefPubMed Fleischmann R et al (2017) Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial. Lancet 390(10093):457–468 CrossRefPubMed
16.
Zurück zum Zitat van der Heijde D et al (2013) 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 Rheum 65(3):559–570 CrossRefPubMed van der Heijde D et al (2013) 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 Rheum 65(3):559–570 CrossRefPubMed
19.
Zurück zum Zitat Wollenhaupt J et al (2019) Safety and efficacy of tofacitinib for up to 9.5 years in the treatment of rheumatoid arthritis: final results of a global, open-label, long-term extension study. Arthritis Res Ther 21(1):89 PubMedPubMedCentralCrossRef Wollenhaupt J et al (2019) Safety and efficacy of tofacitinib for up to 9.5 years in the treatment of rheumatoid arthritis: final results of a global, open-label, long-term extension study. Arthritis Res Ther 21(1):89 PubMedPubMedCentralCrossRef
20.
Zurück zum Zitat Fleischmann R et al (2017) Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Rheumatol 69(3):506–517 PubMedPubMedCentralCrossRef Fleischmann R et al (2017) Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Rheumatol 69(3):506–517 PubMedPubMedCentralCrossRef
21.
Zurück zum Zitat Dougados M et al (2017) Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study. Ann Rheum Dis 76(1):88–95 CrossRefPubMed Dougados M et al (2017) Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study. Ann Rheum Dis 76(1):88–95 CrossRefPubMed
22.
Zurück zum Zitat Taylor PC et al (2017) Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med 376(7):652–662 CrossRefPubMed Taylor PC et al (2017) Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med 376(7):652–662 CrossRefPubMed
23.
Zurück zum Zitat Genovese MC et al (2016) Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med 374(13):1243–1252 CrossRefPubMed Genovese MC et al (2016) Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med 374(13):1243–1252 CrossRefPubMed
24.
Zurück zum Zitat Emery P et al (2017) Patient-reported outcomes from a phase III study of baricitinib in patients with conventional synthetic DMARD-refractory rheumatoid arthritis. RMD Open 3(1):e410 PubMedPubMedCentralCrossRef Emery P et al (2017) Patient-reported outcomes from a phase III study of baricitinib in patients with conventional synthetic DMARD-refractory rheumatoid arthritis. RMD Open 3(1):e410 PubMedPubMedCentralCrossRef
25.
Zurück zum Zitat Smolen JS et al (2017) Patient-reported outcomes from a randomised phase III study of baricitinib in patients with rheumatoid arthritis and an inadequate response to biological agents (RA-BEACON). Ann Rheum Dis 76(4):694–700 CrossRefPubMed Smolen JS et al (2017) Patient-reported outcomes from a randomised phase III study of baricitinib in patients with rheumatoid arthritis and an inadequate response to biological agents (RA-BEACON). Ann Rheum Dis 76(4):694–700 CrossRefPubMed
26.
Zurück zum Zitat Schiff M et al (2017) Patient-reported outcomes of baricitinib in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Res Ther 19(1):208 PubMedPubMedCentralCrossRef Schiff M et al (2017) Patient-reported outcomes of baricitinib in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Res Ther 19(1):208 PubMedPubMedCentralCrossRef
27.
Zurück zum Zitat Keystone EC et al (2017) Patient-reported outcomes from a phase 3 study of baricitinib versus placebo or adalimumab in rheumatoid arthritis: secondary analyses from the RA-BEAM study. Ann Rheum Dis 76(11):1853–1861 PubMedCrossRef Keystone EC et al (2017) Patient-reported outcomes from a phase 3 study of baricitinib versus placebo or adalimumab in rheumatoid arthritis: secondary analyses from the RA-BEAM study. Ann Rheum Dis 76(11):1853–1861 PubMedCrossRef
28.
Zurück zum Zitat Takeuchi T et al (2019) Dose reduction of baricitinib in patients with rheumatoid arthritis achieving sustained disease control: results of a prospective study. Ann Rheum Dis 78(2):171–178 CrossRefPubMed Takeuchi T et al (2019) Dose reduction of baricitinib in patients with rheumatoid arthritis achieving sustained disease control: results of a prospective study. Ann Rheum Dis 78(2):171–178 CrossRefPubMed
31.
Zurück zum Zitat Markham A, Keam Peficitinib SJ (2019) Peficitinib: first global approval. Drugs 79(8):887–891 PubMedCrossRef Markham A, Keam Peficitinib SJ (2019) Peficitinib: first global approval. Drugs 79(8):887–891 PubMedCrossRef
32.
Zurück zum Zitat Takeuchi T et al (2019) Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III randomised, double-blind, placebo-controlled trial (RAJ4) in Japan. Ann Rheum Dis 78(10):1305–1319 Takeuchi T et al (2019) Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III randomised, double-blind, placebo-controlled trial (RAJ4) in Japan. Ann Rheum Dis 78(10):1305–1319
33.
Zurück zum Zitat Tanaka Y et al (2019) Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to conventional DMARDs: a randomised, double-blind, placebo-controlled phase III trial (RAJ3). Ann Rheum Dis 78(10):1320–1332 Tanaka Y et al (2019) Efficacy and safety of peficitinib (ASP015K) in patients with rheumatoid arthritis and an inadequate response to conventional DMARDs: a randomised, double-blind, placebo-controlled phase III trial (RAJ3). Ann Rheum Dis 78(10):1320–1332
34.
Zurück zum Zitat Genovese MC et al (2019) 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 322(4):315–325 PubMedPubMedCentralCrossRef Genovese MC et al (2019) 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 322(4):315–325 PubMedPubMedCentralCrossRef
35.
Zurück zum Zitat Genovese M et al (2018) Effect of filgotinib, a selective JAK 1 inhibitor, with and without methotrexate in patients with rheumatoid arthritis: patient-reported outcomes. Arthritis Res Ther 20(1):57 PubMedPubMedCentralCrossRef Genovese M et al (2018) Effect of filgotinib, a selective JAK 1 inhibitor, with and without methotrexate in patients with rheumatoid arthritis: patient-reported outcomes. Arthritis Res Ther 20(1):57 PubMedPubMedCentralCrossRef
36.
Zurück zum Zitat Burmester GR et al (2018) 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 391(10139):2503–2512 PubMedCrossRef Burmester GR et al (2018) 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 391(10139):2503–2512 PubMedCrossRef
37.
Zurück zum Zitat Smolen JS et al (2019) Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study. Lancet 393(10188):2303–2311 PubMedCrossRef Smolen JS et al (2019) Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study. Lancet 393(10188):2303–2311 PubMedCrossRef
38.
Zurück zum Zitat Genovese MC et al (2018) 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 391(10139):2513–2524 CrossRefPubMed Genovese MC et al (2018) 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 391(10139):2513–2524 CrossRefPubMed
39.
Zurück zum Zitat Fleischmann RM et al (2019) Upadacitinib versus Placebo or Adalimumab in Patients with Rheumatoid Arthritis and an inadequate response to methotrexate: results of a phase III, double-blind, randomized controlled trial. Arthritis Rheumatol 71:1788– 1800 Fleischmann RM et al (2019) Upadacitinib versus Placebo or Adalimumab in Patients with Rheumatoid Arthritis and an inadequate response to methotrexate: results of a phase III, double-blind, randomized controlled trial. Arthritis Rheumatol 71:1788– 1800
40.
Zurück zum Zitat Fleischmann RM et al (2019) Safety and effectiveness of upadacitinib or adalimumab plus methotexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response. Ann Rheum Dis Fleischmann RM et al (2019) Safety and effectiveness of upadacitinib or adalimumab plus methotexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response. Ann Rheum Dis
41.
Zurück zum Zitat v. Vollenhoven R et al (2019) THU0197 monotherapy with upadacitinib in MTX-Naïve patients with rheumatoid arthritis: results at 48 weeks from the select-early study. Ann Rheum Dis 78(Suppl 2):376–377 v. Vollenhoven R et al (2019) THU0197 monotherapy with upadacitinib in MTX-Naïve patients with rheumatoid arthritis: results at 48 weeks from the select-early study. Ann Rheum Dis 78(Suppl 2):376–377
44.
Zurück zum Zitat Asahina A et al (2016) Oral tofacitinib efficacy, safety and tolerability in Japanese patients with moderate to severe plaque psoriasis and psoriatic arthritis: A randomized, double-blind, phase 3 study. J Dermatol 43(8):869–880 PubMedPubMedCentralCrossRef Asahina A et al (2016) Oral tofacitinib efficacy, safety and tolerability in Japanese patients with moderate to severe plaque psoriasis and psoriatic arthritis: A randomized, double-blind, phase 3 study. J Dermatol 43(8):869–880 PubMedPubMedCentralCrossRef
45.
Zurück zum Zitat Mease P et al (2017) Tofacitinib or adalimumab versus placebo for psoriatic arthritis. N Engl J Med 377(16):1537–1550 PubMedCrossRef Mease P et al (2017) Tofacitinib or adalimumab versus placebo for psoriatic arthritis. N Engl J Med 377(16):1537–1550 PubMedCrossRef
46.
Zurück zum Zitat Gladman D et al (2017) Tofacitinib for psoriatic arthritis in patients with an inadequate response to TNF inhibitors. N Engl J Med 377(16):1525–1536 PubMedCrossRef Gladman D et al (2017) Tofacitinib for psoriatic arthritis in patients with an inadequate response to TNF inhibitors. N Engl J Med 377(16):1525–1536 PubMedCrossRef
48.
Zurück zum Zitat Mease P et al (2018) Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo-controlled, phase 2 trial. Lancet 392(10162):2367–2377 CrossRefPubMed Mease P et al (2018) Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo-controlled, phase 2 trial. Lancet 392(10162):2367–2377 CrossRefPubMed
50.
Zurück zum Zitat van der Heijde D et al (2017) Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study. Ann Rheum Dis 76(8):1340–1347 PubMedCrossRef van der Heijde D et al (2017) Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study. Ann Rheum Dis 76(8):1340–1347 PubMedCrossRef
51.
Zurück zum Zitat van der Heijde D et al (2018) Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomised, placebo-controlled, phase 2 trial. Lancet 392(10162):2378–2387 CrossRefPubMed van der Heijde D et al (2018) Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomised, placebo-controlled, phase 2 trial. Lancet 392(10162):2378–2387 CrossRefPubMed
52.
Zurück zum Zitat A Study Evaluating the Safety and Efficacy of Upadacitinib in Subjects With Active Ankylosing Spondylitis ( SELECT Axis 1 ) (SELECT Axis 1). ClinicalTrials.gov, Z.a. Zugegriffen: 30. Aug. 2019 A Study Evaluating the Safety and Efficacy of Upadacitinib in Subjects With Active Ankylosing Spondylitis ( SELECT Axis 1 ) (SELECT Axis 1). ClinicalTrials.gov, Z.a. Zugegriffen: 30. Aug. 2019
53.
Zurück zum Zitat Sandborn WJ et al (2017) Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med 376(18):1723–1736 CrossRefPubMed Sandborn WJ et al (2017) Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med 376(18):1723–1736 CrossRefPubMed
54.
Zurück zum Zitat Panes J et al (2018) Tofacitinib in patients with ulcerative colitis: health-related quality of life in phase 3 randomised controlled induction and maintenance studies. J Crohns Colitis 12(2):145–156 CrossRefPubMed Panes J et al (2018) Tofacitinib in patients with ulcerative colitis: health-related quality of life in phase 3 randomised controlled induction and maintenance studies. J Crohns Colitis 12(2):145–156 CrossRefPubMed
57.
Zurück zum Zitat Sands BE et al (2018) Peficitinib, an oral Janus Kinase inhibitor, in moderate-to-severe ulcerative colitis: results from a randomised, phase 2 study. J Crohns Colitis 12(10):1158–1169 CrossRefPubMed Sands BE et al (2018) Peficitinib, an oral Janus Kinase inhibitor, in moderate-to-severe ulcerative colitis: results from a randomised, phase 2 study. J Crohns Colitis 12(10):1158–1169 CrossRefPubMed
59.
Zurück zum Zitat Levy LL, Urban J, King BA (2015) Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate. J Am Acad Dermatol 73(3):395–399 CrossRefPubMed Levy LL, Urban J, King BA (2015) Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate. J Am Acad Dermatol 73(3):395–399 CrossRefPubMed
60.
Zurück zum Zitat Bissonnette R et al (2016) Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol 175(5):902–911 CrossRefPubMed Bissonnette R et al (2016) Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol 175(5):902–911 CrossRefPubMed
61.
Zurück zum Zitat Guttman-Yassky E et al (2019) Baricitinib in adult patients with moderate-to-severe atopic dermatitis: A phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study. J Am Acad Dermatol 80(4):913–921e9 CrossRefPubMed Guttman-Yassky E et al (2019) Baricitinib in adult patients with moderate-to-severe atopic dermatitis: A phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study. J Am Acad Dermatol 80(4):913–921e9 CrossRefPubMed
62.
Zurück zum Zitat Lilly’s BREEZE-AD1 & BREEZE-AD2 phase 3 studies of baricitinib in patients with moderate to severe AD meets primary endpoint. Indianapolis: Pharmabiz.com, Z.a. Zugegriffen: 30. Aug. 2019 Lilly’s BREEZE-AD1 & BREEZE-AD2 phase 3 studies of baricitinib in patients with moderate to severe AD meets primary endpoint. Indianapolis: Pharmabiz.com, Z.a. Zugegriffen: 30. Aug. 2019
64.
Zurück zum Zitat Wallace DJ et al (2018) Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet 392(10143):222–231 PubMedCrossRef Wallace DJ et al (2018) Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet 392(10143):222–231 PubMedCrossRef
66.
Zurück zum Zitat A Study to Investigate the Safety and Efficacy of ABBV-105 and Upadacitinib Given Alone or in Combination in Participants With Moderately to Severely Active Systemic Lupus Erythematosus. ClinicalTrials.gov. Zugegriffen: 30. Aug. 2019 A Study to Investigate the Safety and Efficacy of ABBV-105 and Upadacitinib Given Alone or in Combination in Participants With Moderately to Severely Active Systemic Lupus Erythematosus. ClinicalTrials.gov. Zugegriffen: 30. Aug. 2019
68.
Zurück zum Zitat Cohen S et al (2018) Worldwide, 3‑year, post-marketing surveillance experience with tofacitinib in rheumatoid arthritis. Rheumatol Ther 5(1):283–291 PubMedPubMedCentralCrossRef Cohen S et al (2018) Worldwide, 3‑year, post-marketing surveillance experience with tofacitinib in rheumatoid arthritis. Rheumatol Ther 5(1):283–291 PubMedPubMedCentralCrossRef
69.
Zurück zum Zitat Cohen SB et al (2017) 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 76(7):1253–1262 PubMedCrossRef Cohen SB et al (2017) 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 76(7):1253–1262 PubMedCrossRef
70.
Zurück zum Zitat Strand V et al (2015) Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials. Arthritis Res Ther 17:362 PubMedPubMedCentralCrossRef Strand V et al (2015) Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials. Arthritis Res Ther 17:362 PubMedPubMedCentralCrossRef
71.
Zurück zum Zitat Curtis JR et al (2016) Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis. Ann Rheum Dis 75(10):1843–1847 PubMedCrossRef Curtis JR et al (2016) Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis. Ann Rheum Dis 75(10):1843–1847 PubMedCrossRef
72.
Zurück zum Zitat Winthrop KL et al (2017) Herpes zoster and tofacitinib: clinical outcomes and the risk of concomitant therapy. Arthritis Rheumatol 69(10):1960–1968 PubMedPubMedCentralCrossRef Winthrop KL et al (2017) Herpes zoster and tofacitinib: clinical outcomes and the risk of concomitant therapy. Arthritis Rheumatol 69(10):1960–1968 PubMedPubMedCentralCrossRef
73.
Zurück zum Zitat Winthrop KL et al (2017) The safety and immunogenicity of live zoster vaccination in patients with rheumatoid arthritis before starting tofacitinib: a randomized phase II trial. Arthritis Rheumatol 69(10):1969–1977 PubMedPubMedCentralCrossRef Winthrop KL et al (2017) The safety and immunogenicity of live zoster vaccination in patients with rheumatoid arthritis before starting tofacitinib: a randomized phase II trial. Arthritis Rheumatol 69(10):1969–1977 PubMedPubMedCentralCrossRef
74.
Zurück zum Zitat Smolen JS et al (2019) Safety profile of baricitinib in patients with active rheumatoid arthritis with over 2 years median time in treatment. J Rheumatol 46(1):7–18 PubMedCrossRef Smolen JS et al (2019) Safety profile of baricitinib in patients with active rheumatoid arthritis with over 2 years median time in treatment. J Rheumatol 46(1):7–18 PubMedCrossRef
75.
Zurück zum Zitat Schulze-Koops H et al (2016) Analysis of haematological changes in tofacitinib-treated patients with rheumatoid arthritis across phase 3 and long-term extension studies. Baillieres Clin Rheumatol 56(1):46–57 Schulze-Koops H et al (2016) Analysis of haematological changes in tofacitinib-treated patients with rheumatoid arthritis across phase 3 and long-term extension studies. Baillieres Clin Rheumatol 56(1):46–57
76.
77.
Zurück zum Zitat Ogdie A et al (2018) Risk of venous thromboembolism in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a general population-based cohort study. Eur Heart J 39(39):3608–3614 PubMedCrossRef Ogdie A et al (2018) Risk of venous thromboembolism in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a general population-based cohort study. Eur Heart J 39(39):3608–3614 PubMedCrossRef
78.
Zurück zum Zitat Hoppe B, Dörner T (2012) Coagulation and the fibrin network in rheumatic disease: a role beyond haemostasis. Nat Rev Rheumatol 8:738 PubMedCrossRef Hoppe B, Dörner T (2012) Coagulation and the fibrin network in rheumatic disease: a role beyond haemostasis. Nat Rev Rheumatol 8:738 PubMedCrossRef
79.
Zurück zum Zitat McInnes IB et al (2015) Effect of interleukin‑6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study. Ann Rheum Dis 74(4):694–702 PubMedCrossRef McInnes IB et al (2015) Effect of interleukin‑6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study. Ann Rheum Dis 74(4):694–702 PubMedCrossRef
80.
Zurück zum Zitat Strangfeld A et al (2017) Risk for lower intestinal perforations in patients with rheumatoid arthritis treated with tocilizumab in comparison to treatment with other biologic or conventional synthetic DMARDs. Ann Rheum Dis 76(3):504–510 PubMedCrossRef Strangfeld A et al (2017) Risk for lower intestinal perforations in patients with rheumatoid arthritis treated with tocilizumab in comparison to treatment with other biologic or conventional synthetic DMARDs. Ann Rheum Dis 76(3):504–510 PubMedCrossRef
81.
Zurück zum Zitat Mariette X et al (2018) Lymphoma in the tofacitinib rheumatoid arthritis clinical development program. Arthritis Care Res 70(5):685–694 CrossRef Mariette X et al (2018) Lymphoma in the tofacitinib rheumatoid arthritis clinical development program. Arthritis Care Res 70(5):685–694 CrossRef
Metadaten
Titel
Januskinase-Inhibitoren
State of the Art im klinischen Einsatz und Zukunftsperspektiven
verfasst von
Prof. Dr. R. Alten
M. Mischkewitz
A.-L. Stefanski
T. Dörner
Publikationsdatum
07.08.2020
Verlag
Springer Vienna
Schlagwort
Rheumatologie
Erschienen in
rheuma plus / Ausgabe 6/2020
Print ISSN: 1868-260X
Elektronische ISSN: 2191-2610
DOI
https://doi.org/10.1007/s12688-020-00364-0

Weitere Artikel der Ausgabe 6/2020

rheuma plus 6/2020 Zur Ausgabe