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Arthritis und Rheuma 2024; 44(02): 95-100
DOI: 10.1055/a-2214-5085
Schwerpunkt

Interferon-Inhibition beim systemischen Lupus erythematodes

Johanna Mucke
1   Klinik für Rheumatologie, Medizinische Fakultät und Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf
1   Klinik für Rheumatologie, Medizinische Fakultät und Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität Düsseldorf
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ZUSAMMENFASSUNG

Typ-I-Interferone (IFN) spielen über die Bindung an den Interferon-alpha-Rezeptor und die Aktivierung des JAK-STAT-Weges eine wichtige Rolle in der Abwehr viraler Organismen. Beim SLE findet sich eine Überproduktion von Typ-I-IFN, die zu einer vermehrten Aktivierung von B-Zellen führen. Die IFN-Level korrelieren dabei mit Krankheitsaktivität und -schwere. Typ-I-IFN stellen damit ein vielversprechendes Therapieziel dar und mit der Zulassung des IFN-alpha-Rezeptor-Inhibitors Anifrolumab zur Therapie des extrarenalen SLE steht bereits ein wirksames Medikament zur Interferon-Blockade zu Verfügung. Zudem gibt es weitere Ansätze, wie die JAK-Inhibition oder Hemmung der IFN-produzierenden plasmazytoiden dendritischen Zellen, die derzeit als mögliche Therapieziele bei SLE getestet werden.

Schlüsselwörter

Systemischer Lupus erythematodes - IFN-Inhibition - Antikörpertherapie


Publication History

Article published online:
16 April 2024

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  • Literatur

  • 1 Tsokos GC, Lo MS, Costa Reis P. et al New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol 2016; 12: 716-730
    CrossrefPubMedSearch in Google Scholar
  • 2 Herrada AA, Escobedo N, Iruretagoyena M. et al Innate Immune Cells’ Contribution to Systemic Lupus Erythematosus. Front Immunol 2019; 10: 772
    CrossrefPubMedSearch in Google Scholar
  • 3 Rönnblom L, Pascual V. The innate immune system in SLE: type I interferons and dendritic cells. Lupus 2008; 17: 394-399
    CrossrefPubMedSearch in Google Scholar
  • 4 Bruera S, Chavula T, Madan R. et al Targeting type I interferons in systemic lupus erythematous. Front Pharmacol 2022; 13: 1046687
    CrossrefPubMedSearch in Google Scholar
  • 5 Kim J-M, Park S-H, Kim H-Y. et al A Plasmacytoid Dendritic Cells-Type I Interferon Axis Is Critically Implicated in the Pathogenesis of Systemic Lupus Erythematosus. Int J Mol Sci 2015; 16: 14158-14170
    CrossrefPubMedSearch in Google Scholar
  • 6 Montoya M, Schiavoni G, Mattei F. et al Type I interferons produced by dendritic cells promote their phenotypic and functional activation. Blood 2002; 99: 3263-3271
    CrossrefPubMedSearch in Google Scholar
  • 7 Choi J, Kim ST, Craft J. The pathogenesis of systemic lupus erythematosus-an update. Curr Opin Immunol 2012; 24: 651-657
    CrossrefPubMedSearch in Google Scholar
  • 8 Wahadat MJ, Bodewes ILA, Maria NI. et al Type I IFN signature in childhood-onset systemic lupus erythematosus: a conspiracy of DNA- and RNA-sensing receptors?. Arthritis Res Ther 2018; 20: 4
    CrossrefPubMedSearch in Google Scholar
  • 9 Khamashta M, Merrill JT, Werth VP. et al Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study. Ann Rheum Dis 2016; 75: 1909-1916
    CrossrefPubMedSearch in Google Scholar
  • 10 Kalunian KC, Merrill JT, Maciuca R. et al A Phase II study of the efficacy and safety of rontalizumab (rhuMAb interferon-α) in patients with systemic lupus erythematosus (ROSE). Ann Rheum Dis 2016; 75: 196-202
    CrossrefPubMedSearch in Google Scholar
  • 11 Houssiau FA, Thanou A, Mazur M. et al IFN-α kinoid in systemic lupus erythematosus: results from a phase IIb, randomised, placebo-controlled study. Ann Rheum Dis 2020; 79: 347-355
    CrossrefPubMedSearch in Google Scholar
  • 12 Furie R, Khamashta M, Merrill JT. et al Anifrolumab, an Anti-Interferon-α Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus. Arthritis & rheumatology (Hoboken, N.J.) 2017; 69: 376-386
    CrossrefPubMedSearch in Google Scholar
  • 13 Furie RA, Morand EF, Bruce IN. et al Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. The Lancet Rheumatology 2019; 01: e208-e219
    CrossrefPubMedSearch in Google Scholar
  • 14 Morand EF, Furie R, Tanaka Y. et al Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med 2020; 382: 211-221
    CrossrefPubMedSearch in Google Scholar
  • 15 Furie R, Morand EF, Askanase AD. et al Anifrolumab reduces flare rates in patients with moderate to severe systemic lupus erythematosus. Lupus 2021; 30: 1254-1263
    CrossrefPubMedSearch in Google Scholar
  • 16 Bruce IN, van Vollenhoven RF, Psachoulia K. et al Time to onset of clinical response to anifrolumab in patients with SLE: pooled data from the phase III TULIP-1 and TULIP-2 trials. Lupus Sci Med 2023: 10
    CrossrefPubMedSearch in Google Scholar
  • 17 Kalunian KC, Furie R, Morand EF. et al A Randomized, Placebo-Controlled Phase III Extension Trial of the Long-Term Safety and Tolerability of Anifrolumab in Active Systemic Lupus Erythematosus. Arthritis & rheumatology (Hoboken, N.J./USA) 2023; 75: 253-265
    CrossrefPubMedSearch in Google Scholar
  • 18 Fanouriakis A, Kostopoulo M, Andersen J. et al Eular recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis 2024; 83 (01) 15-29
    CrossrefPubMedSearch in Google Scholar
  • 19 Jayne D, Rovin B, Mysler E. et al Anifrolumab in lupus nephritis: results from second-year extension of a randomised phase II trial. Lupus Sci Med 2023; 10 (02) e000910
    CrossrefPubMedSearch in Google Scholar
  • 20 Furie RA, van Vollenhoven RF, Kalunian K. et al Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus. N Engl J Med 2022; 387: 894-904
    CrossrefPubMedSearch in Google Scholar
  • 21 Werth VP, Furie RA, Romero-Diaz J. et al Trial of Anti-BDCA2 Antibody Litifilimab for Cutaneous Lupus Erythematosus. N Engl J Med 2022; 387: 321-331
    CrossrefPubMedSearch in Google Scholar
  • 22 Wallace DJ, Gudsoorkar VS, Weisman MH. et al New insights into mechanisms of therapeutic effects of antimalarial agents in SLE. Nat Rev Rheumatol 2012; 08: 522-533
    CrossrefPubMedSearch in Google Scholar
  • 23 Morand EF, Vital EM, Petri M. et al Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-I). Lancet 2023; 401: 1001-1010
    CrossrefPubMedSearch in Google Scholar
  • 24 Petri M, Bruce IN, Dörner T. et al Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-II). Lancet 2023; 401: 1011-1019
    CrossrefPubMedSearch in Google Scholar
  • 25 Merrill JT, Tanaka Y, D’cruz D. et al OP0139 Efficacy and safety of ABBV-599 high dose (Elsubrutinib 60 mg and Upadacitinib 30 mg) and Upadacitinib monotherapy for the treatment of systemic lupus erythemotosus: a phase 2, double-blind, placebo-controlled trial. In: Scientific Abstracts. BMJ Publishing Group Ltd and European League Against Rheumatism. 2023: 91-92
    CrossrefSearch in Google Scholar
  • 26 Morand E, Pike M, Merrill JT. et al Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis & rheumatology (Hoboken, N.J./USA) 2023; 75: 242-252
    CrossrefPubMedSearch in Google Scholar