Skip to main content
SpringerLink
Log in

Infektionsrisiko durch Biologika

Risk of infection by biologics

  • Leitthema
  • Published:
Zeitschrift für Rheumatologie Aims and scope Submit manuscript

Zusammenfassung

Tumor-Nekrose-Faktor- (TNF-)α spielt eine essenzielle Rolle in der Vermittlung und Aufrechterhaltung entzündlicher Prozesse, sowohl bei Autoimmunerkrankungen als auch in der Infektabwehr einschließlich der Granulomformation. TNF-α-Antagonisten sind hocheffektiv in der Therapie der rheumatoiden Arhritis (RA) und weiterer Autoimmunerkrankungen. Sie kompromittieren jedoch die ohnehin durch eine Autoimmunerkrankung reduzierte Infektabwehr, insbesondere bei der Kontrolle von Infektionen, die mit einer Granulombildung einhergehen, wie z. B. der Tuberkulose. Weitere Biologika mit anderen Wirkprinzipien wie Inhibition von Interleukin- (IL-)1 (Anakinra), B-Zell-Depletion (Rituximab) und Blockierung der T-Zell-Kostimulation (Abatacept) sind mittlerweile entwickelt und für die Therapie der RA zugelassen. Nach anfänglicher Skepsis, die insbesondere durch die erhöhte Inzidenz von Tuberkulosereaktivierungen unter TNF-α-Antagonisten geschürt wurde, haben Biologika heute eine feste Rolle in der Anwendung als Immunsuppressiva bei verschiedenen Autoimmunerkrankungen. Zur Reduktion unerwünschter Nebenwirkungen – vor allem von Infektionen – gibt es heute Richtlinien für Screening-Untersuchungen und Verlaufskontrollen. Die Effizienz dieser Untersuchungen und Kontrollen wurde eindrucksvoll anhand der drastischen Reduktion der Tuberkulosefälle unter der Therapie mit TNF-α-Antagonisten belegt. Diese Übersicht fasst die aktuelle Datenlage hinsichtlich des Infektionsrisikos der Biologika zusammen und gibt Aufschluss über notwendige Screening-Untersuchungen und Verlaufskontrollen vor und unter Therapie, um Nebenwirkungen wie Infektionen zu vermeiden oder frühzeitig zu erkennen sowie Kontraindikationen und Abbruchgründe.

Abstract

Tumor necrosis factor (TNF-α) plays an essential role in the orchestration of inflammatory processes including autoimmune disorders, host defence and granuloma formation. TNF antagonists are highly effective in the therapy of rheumatoid arthritis, but they compromise host defence mechanisms, especially concerning bacterial infections inducing granuloma formation, such as tuberculosis. Other biologics have been developed and approved for the therapy of rheumatoid arthritis, e.g. an interleukin (IL-1) blocking agent (anakinra), an antibody that depletes CD20 positive B-cells (rituximab) and an inhibitor of T-cell co-stimulation (abatacept). In spite of initial skepticism regarding side effects, such as an increased risk of infections, biologics now play an essential role in the therapy of autoimmune diseases due to the implementation of efficient screening measures concerning side effects (such as reactivation of tuberculosis). This review summarizes the current available data regarding risk of infection and gives and overview on recommended screening, contraindications and events that require withdrawal of therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Askling J, Fored CM (2007) Time-dependent increase in risk of hospitalization with infection among Swedish RA patients treated with TNF antagonists. Ann Rheum Dis 66: 1339–1344

    Article  PubMed  Google Scholar 

  2. Bigbee CL, Gonchoroff DG (2007) Abatacept treatment does not exacerbate chronic mycobacterium tuberculosis infection in mice. Arthritis Rheum 56: 2557–2565

    Article  PubMed  CAS  Google Scholar 

  3. Bongartz T, Sutton AJ (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies. Systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295: 2275–2482

    Article  PubMed  CAS  Google Scholar 

  4. British Thoracic Society Standards of Care Committee (2005) BTS recommendations for asessing risk and for managing Mycobacterium tuberculosis infection and disease in patients due to start anti-TNF-a treatment. Thorax 60: 800–805

    Article  Google Scholar 

  5. Carmona L, Gomet-Reino JJ (2005) Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. Arthritis Rheum 52: 1766–1772

    Article  PubMed  CAS  Google Scholar 

  6. Carroll MB, Bond ML (2008) Use of tumor necrosis factor-alpha inhibitors in patients with chronic hepatitis B infection. Semin Arthritis Rheum [Epub ahead of print]

  7. Cepeda EJ, Williams FM (2007) The use of anti-tumor necrosis factor therapy in HIV positive individuals with rheumatic disease. Ann Rheum Dis 76: 710–712

    Article  CAS  Google Scholar 

  8. Curtis JR, Patkar N (2007) Risk of serious infections among rheumatoid arthritis patients exposed to tumor necrosis factor alpha antagonists. Arthritis Rheum 56: 1125–1133

    Article  PubMed  CAS  Google Scholar 

  9. Denis B, Lefort A (2008) Long-term follow-up of patients with tuberculosis as a complication of tumor necrosis (TNF)-α antagonist therapy: safe re-initiation of TNF-α blockers after appropriate anti-tuberculous treatment. Clin Microbiol Infect 14: 183–186

    PubMed  CAS  Google Scholar 

  10. Dixon WG, Watson K (2006) Rates of serious infection, including site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti-tumor necrosis factor therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum 54: 2368–2376

    Article  PubMed  CAS  Google Scholar 

  11. Dixon WG, Symmons DPM, Lunt M et al. (2007) Serious infection following anti-tumor necrosis factor α therapy in patients with rheumatoid arthritis: lessons form interpreting data from observational studies. Arthritis Rheum 56: 2896–2904

    Article  PubMed  CAS  Google Scholar 

  12. Eissner G, Kolch W (2004) Ligands working as receptors: reverse signaling by members of the TNF superfamily enhance the plasticity of the immune system. Cytokine Growth Factor Rev 15: 353–366

    Article  PubMed  CAS  Google Scholar 

  13. Fachinformation Anakinra, Stand 2003

  14. Fachinformation Orencia, Stand: Mai 2007

  15. Fachinformation MabThera, Stand Januar 2008

  16. Ferrara G, Losi M (2005) Routine hospital use of a new commercial whole blood interferon-gamma assay for the diagnosis of tuberculosis infection. Am J Respir Crit Care Med 172: 631–635

    Article  PubMed  Google Scholar 

  17. Ferrara G, Losi M (2006) Use in routine clinical practice of two commercial blood tests for diagnosis of infection with mycobacterium tuberculosis: a prospective study. Lancet 367: 1328–1334

    Article  PubMed  CAS  Google Scholar 

  18. Fleischmann R, Schechtmann J (2003) Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis: a large, international, multicenter, placebo-controlled trial. Arthritis Rheum 48: 927–934

    Article  PubMed  CAS  Google Scholar 

  19. Fleischmann RM (2006) Safety of extended treatment in patients with rheumatoid arthritis. Ann Rheum Dis 65: 1006–1012

    Article  PubMed  CAS  Google Scholar 

  20. Furst DE, Breedveld FC (2007) Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007. Ann Rheum Dis 66: 2–22

    Google Scholar 

  21. Gomez-Reino JJ, Carmona L for the BIOBADASER Group (2007) Risk of tuberculosis in patients treated with tumor necrosis factor a antagonists due to incomplete prevention of reactivation of latent infection. Arthritis Rheum 57: 756–761

    Article  PubMed  CAS  Google Scholar 

  22. Listing J, Strangfeld A (2005) Infections in patients with rheumatoid arthritis treated with biologic agents. Arthritis Rheum 52: 3404–3412

    Article  CAS  Google Scholar 

  23. Matulis G Jüni P (2008) Detection of latent tuberculosis in immunosuppressed patients with autoimmune disease: performance of a Mycobacterium tuberculosis antigen-specific interferon gamma assay. Ann Rheum Dis 67: 84–90

    Article  PubMed  CAS  Google Scholar 

  24. Patkar N, Teng GG (2008) Association of infections and tuberculosis with antitumor necrosis factor alpha therapy. Curr Opin Rheumatol 20: 320–326

    Article  PubMed  CAS  Google Scholar 

  25. Peterson JR, Hsu FC (2003) Effect of tumor necrosis factor alpha antagonists on serum transaminases and viremia in patients with rheumatoid arthritis and chronic hepatitis C infection. Ann Rheum Dis 62: 1078–1082

    Article  PubMed  CAS  Google Scholar 

  26. Salliot C, Dougados M (2008) Risk of serious infections during rituximab, abatacept and anakinra therapies for rheumatoid arthritis: meta-analysis of randomized placebo-controlled trials. Ann Rheum Dis [Epub 18 Jan 2008]

  27. Schneeweiss S, Setoguchi, Weinblatt ME et al. (2007) Anti-tumor necrosis factor α therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis. Arthritis Rheum 56: 1754–1764

    Article  PubMed  CAS  Google Scholar 

  28. Tracey D, Klareskog L (2008) Tumor necrosis factor antagonist mechanism of action: a comprehensive review. Pharm Ther 117: 224–279

    Google Scholar 

  29. Tsiodras S, Samonis G (2008) Fungal infections complicating tumor necrosis factor blockade therapy. Mayo Clin Proc 83: 181–194

    Article  PubMed  CAS  Google Scholar 

  30. Tubach F, Ravaud P (2006) Emergence of Legionella pneumophila penumonia in patients receiving tumor necrosis factor-alpha antagonists. Clin Infect Dis 43: e95–e100

    Article  PubMed  CAS  Google Scholar 

  31. Wallis RS, Kyambadde P (2004) A study of safety, immunology, virology, and microbiology of adjunctive etanercept in HIV-1-associated tuberculosis. AIDS 18: 257–264

    Article  PubMed  CAS  Google Scholar 

  32. Westhovens R, Yocum D (2006) The safety of infliximab, combined with background treatments among patients with rheumatoid arthritis and various comorbidities: a large, randomized, controlled, placebo-controlled trial. Arthritis Rheum 54: 1075–1086

    Article  PubMed  CAS  Google Scholar 

  33. Wolfe F, Caplan L, Michaud K (2006) Treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy. Arthritis Rheum 54: 628–634

    Article  PubMed  CAS  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Poliklinik für Rheumatologie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 24576, Lübeck, Deutschland

    J.U. Holle, S. Schinke & W.L. Gross

Authors
  1. J.U. Holle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Schinke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W.L. Gross
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J.U. Holle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Holle, J., Schinke, S. & Gross, W. Infektionsrisiko durch Biologika. Z. Rheumatol. 67, 295–304 (2008). https://doi.org/10.1007/s00393-008-0307-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00393-008-0307-4

Schlüsselwörter

Keywords

Search

Navigation