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Biologikatherapie bei rheumatologischen Erkrankungen

Biological therapy for the treatment of rheumatic diseases

  • Schwerpunkt: Biologika in der Therapie
  • Published:
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Zusammenfassung

Seit etwa 25 Jahren hat die Analyse von Zytokinen (Interleukine, Interferone, Kolonie stimulierende Faktoren) die Erkenntnisse der Pathophysiologie und daraus folgend die Therapie der rheumatoiden Arthritis (RA) revolutioniert. Als proinflammatorische Zytokine stellten sich u. a. Tumornekrosefaktor-α (TNF-α), Interleukin-1 (IL-1) und -6 (IL-6) heraus. Insbesondere TNF-α spielt eine zentrale Rolle, und es wurden große Anstrengungen unternommen, eine gegen TNF-α gerichtete RA-Therapie zu etablieren. Bereits 1992 wurde die erste Studie mit einem monoklonalen Antikörper gegen TNF-α durchgeführt, die das therapeutische Prinzip eindrucksvoll bestätigte. Bis heute sind folgende Biologika in der Therapie rheumatologischer Krankheitsbilder etabliert: die Anti-TNF-Therapeutika Etanercept, Infliximab und Adalimumab, der Interleukin-1-Rezeptor-Antagonist Anakinra, der gegen B-Lymphozyten gerichtete Antikörper Rituximab und das gegen CD80/86 gerichtete Fusionsprotein Abatacept. Im vorliegenden Beitrag werden die Modalitäten der Biologikatherapie in der Rheumatologie dargestellt und ein Ausblick auf zu erwartende Behandlungen gegeben.

Abstract

The analysis of cytokines (i.e. interleukins, interferons and colony-stimulating factors) has only flourished in the last 25 years subsequently revealing new insights into the pathogenesis of rheumatic diseases that revolutionised the management of patients with chronic rheumatic disorders. Tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) have been found to play a pivotal role in rheumatic inflammation. As early as in 1992 the first proof of concept study with a monoclonal antibody against TNF was able to demonstrate positive effects in rheumatoid arthritis. Since the approval of the first anti-TNF-α therapy, further agents against TNF and other proinflammatory cytokines were approved and even more biological drugs are under development aimed at modulating the disturbed immune system in patients with rheumatic diseases. To date the following biologics are approved for therapy of chronic rheumatic diseases: the TNF antagonists Etanercept, Infliximab and Adalimumab; Anakinra as an IL-1 receptor antagonist; the anti-CD20 monoclonal antibody Rituximab and the anti-CD80/86 fusion protein Abatacept. In the present article, we report on biological therapy modalities in rheumatic diseases as well as the recommendations for initiation of these agents.

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Abb. 1

Abbreviations

ACR:

American College of Rheumatology

ANCA:

Anti-Neutrophilen-zytoplasmatische Antikörper

AS:

Ankylosierende Spondylitis

BASDAI:

Bath Ankylosing Spondylitis Disease Activity Score

BSG:

Blutkörperchensenkungsgeschwindigkeit

CCP:

Zyklisches zitrulliniertes Peptid

CCR5:

Chemokinrezeptor 5

CD:

„cluster of differentiation“

CINCA:

„chronic infantile neurological cutaneous and articular syndrome“

COPD:

Chronische Lungenerkrankung („chronic obstructive pulmonary disease“)

CTLA:

T-Lymphozyten-Antigen 4

DAS:

„disease activity score“

DGRh:

Deutsche Gesellschaft für Rheumatologie

DMARD:

„disease modifyig antirheumatic drugs“

EULAR:

European League Against Rheumatism

Fc:

Konstante Region („fragment crystallizable region“) der Antikörper

FCAS:

Familiäres kälteinduziertes autoinflammatorisches Syndrom

Fv:

Variable Region der Antikörper

HAQ:

„health assessment questionnaire“

HIV:

Humanes Immundefizienzvirus

HLA:

Humanes Leukozytenantigen („human leucocyte antigen“)

IFN:

Interferon

IgG1:

Humanes Immunglobulin G1

IL-1:

Interleukin-1

IL-6:

Interleukin-6

INH:

Isoniazid

JIA:

Juvenile idiopathische Arthritis

MRT:

Magnetresonanztomographie

Mtx:

Methotrexat

NSAR:

Nichtsteroidale Antirheumatika

RA:

Rheumatoide Arthritis

SLE:

Systemischer Lupus erythematodes

Tb:

Tuberkulose

Th1-Zellen:

T-Helfer-Zellen 1

TNF-α:

Tumornekrosefaktor-α

Treg:

Regulatorische T-Zellen

VAS:

Visuelle Analogskala

Literatur

  1. Abrams JR, Lebwohl MG, Guzzo CA et al. (1999) CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris. J Clin Invest 103: 1243–1252

    Article  PubMed  CAS  Google Scholar 

  2. Aringer M, Smolen JS (2004) Tumour necrosis factor and other proinflammatory cytokines in systemic lupus erythematosus: a rationale for therapeutic intervention. Lupus 13: 344–347

    Article  PubMed  CAS  Google Scholar 

  3. Askling J, Bongartz T (2008) Malignancy and biologic therapy in rheumatoid arthritis. Curr Opin Rheumatol 20: 334–339

    Article  PubMed  CAS  Google Scholar 

  4. Braun J, Sieper J (2007) Ankylosing spondylitis. Lancet 369: 1379–1390

    Article  PubMed  Google Scholar 

  5. Brezinschek HP, Hofstaetter T, Leeb BF et al. (2008) Immunization of patients with rheumatoid arthritis with antitumor necrosis factor alpha therapy and methotrexate. Curr Opin Rheumatol 20: 295–299

    Article  PubMed  CAS  Google Scholar 

  6. Chitale S, Moots R (2008) Abatacept: the first T lymphocyte co-stimulation modulator, for the treatment of rheumatoid arthritis. Expert Opin Biol Ther 8: 115–122

    Article  PubMed  CAS  Google Scholar 

  7. Chung ES, Packer M, Lo KA et al. (2003) Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF therapy against congestive heart failure (ATTACH) trial. Circulation 107: 3133–3140

    Article  PubMed  CAS  Google Scholar 

  8. Davis JC Jr, Mease PJ (2007) Insights into the pathology and treatment of spondyloarthritis: from the bench to the clinic. Semin Arthritis Rheum 2007 Dec 29 [Epub ahead of print]

  9. Davis JC Jr, Van der Heijde DM, Braun J et al. (2008) Efficacy and safety of up to 192 weeks of etanercept therapy in patients with ankylosing spondylitis. Ann Rheum Dis 67: 346–352

    Article  PubMed  CAS  Google Scholar 

  10. Dixon WG, Watson KD, Lunt M et al. (2007) Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis factor alpha therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum 56: 2905–2912

    Article  PubMed  CAS  Google Scholar 

  11. Dörner T, Burmester GR (2008) New approaches of B-cell-directed therapy: beyond rituximab. Curr Opin Rheumatol 20: 263–268

    PubMed  Google Scholar 

  12. Finckh A, Gabay C (2008) At the horizon of innovative therapy in rheumatology: new biologic agents. Curr Opin Rheumatol 20: 269–275

    Article  PubMed  CAS  Google Scholar 

  13. Furst DE, Breedveld FC, Kalden JR et al. (2007) Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007. Ann Rheum Dis [Suppl 3] 66: III2–III22

  14. Gartlehner G, Hansen RA, Jonas BL et al. (2008) Biologics for the treatment of juvenile idiopathic arthritis: a systematic review and critical analysis of the evidence. Clin Rheumatol 27: 67–76

    Article  PubMed  Google Scholar 

  15. Gödde A, Müller-Ladner U (2006) Therapy for secondary arthropathies: from psoriasis and Reiter’s disease to hemochromatosis. Internist (Berl) 47: 1263–1268

    Google Scholar 

  16. Harrison MJ, Dixon WG, Watson KD et al. (2008) Rates of new-onset psoriasis in patients with rheumatoid arthritis receiving anti-TNF{alpha} therapy. Results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis 2008 Apr 2 [Epub ahead of print]]

  17. Heiberg MS, Nordvag BY, Mikkelsen K et al. (2005) The comparative effectiveness of tumor necrosis factor-blocking agents in patients with rheumatoid arthritis and patients with ankylosing spondylitis: a six-month, longitudinal, observational, multicenter study. Arthritis Rheum 52: 2506–2512

    Article  PubMed  CAS  Google Scholar 

  18. Horneff G (2006) Biologics for treatment of juvenile idiopathic arthritis. Consensus statement of the 7th Worlitzer Expertengesprache 2004 for the German Arbeitsgemeinschaft Kinder- und Jugendrheumatologie. Z Rheumatol 65: 152–158

    Article  PubMed  CAS  Google Scholar 

  19. Hyrich KL, Lunt M, Watson KD et al. (2007) Outcomes after switching from one anti-tumor necrosis factor alpha agent to a second anti-tumor necrosis factor alpha agent in patients with rheumatoid arthritis: results from a large UK national cohort study. Arthritis Rheum 56: 13–20

    Article  PubMed  CAS  Google Scholar 

  20. Lee RW, D’Cruz DP (2008) Novel therapies for anti-neutrophil cytoplasmic antibody-associated vasculitis. Drugs 68: 747–770

    Article  PubMed  CAS  Google Scholar 

  21. Manger B, Michels H, Nüsslein HG et al. (2007) Revision of the recommendations of the Commission on Pharmacotherapy of the German Society for Rheumatology. Therapy with tumour necrosis factor blockers for inflammatory rheumatic illnesses. Z Rheumatol 66: 72–75

    Article  PubMed  CAS  Google Scholar 

  22. Patkar NM, Teng GG, Curtis JR et al. (2008) Association of infections and tuberculosis with antitumor necrosis factor alpha therapy. Curr Opin Rheumatol 20: 320–326

    Article  PubMed  CAS  Google Scholar 

  23. Punzi L, Podswiadek M, Sfriso P et al. (2007) Pathogenetic and clinical rationale for TNF-blocking therapy in psoriatic arthritis. Autoimmun Rev 6: 524–528

    Article  PubMed  CAS  Google Scholar 

  24. Scherer HU, Burmester GR (2006) Biologicals in the treatment of rheumatic diseases. Dtsch Med Wochenschr 131: 2279–2285

    Article  PubMed  CAS  Google Scholar 

  25. Sibilia J, Westhovens R (2007) Safety of T-cell co-stimulation modulation with abatacept in patients with rheumatoid arthritis. Clin Exp Rheumatol 25: S46–S56

    PubMed  CAS  Google Scholar 

  26. Smolen JS, Aletaha D (2008) Activity assessments in rheumatoid arthritis. Curr Opin Rheumatol 20: 306–313

    Article  PubMed  Google Scholar 

  27. Smolen JS, Aletaha D, Koeller M et al. (2007) New therapies for treatment of rheumatoid arthritis. Lancet 370: 1861–1874

    Article  PubMed  CAS  Google Scholar 

  28. Soriano ER, McHugh NJ (2006) Therapies for peripheral joint disease in psoriatic arthritis. A systematic review. J Rheumatol 33: 1422–1430

    PubMed  Google Scholar 

  29. Strand V, Kimberly R, Isaacs JD (2007) Biologic therapies in rheumatology: lessons learned, future directions. Nat Rev Drug Discov 6: 75–92

    Article  PubMed  CAS  Google Scholar 

  30. Toussirot E, Wendling D (2007) The use of TNF-alpha blocking agents in rheumatoid arthritis: an update. Expert Opin Pharmacother 8: 2089–2107

    Article  PubMed  CAS  Google Scholar 

  31. Van der Kooij SM, Allaart CF, Dijkmans BA et al. (2008) Innovative treatment strategies for patients with rheumatoid arthritis. Curr Opin Rheumatol 20: 287–294

    Article  Google Scholar 

  32. Vincenti F (2008) Costimulation blockade in autoimmunity and transplantation. J Allergy Clin Immunol 121: 299–306

    Article  PubMed  CAS  Google Scholar 

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  1. Sektion Rheumatologie/Gerontologie,Medizinische Klinik & Poliklinik II, Universitätsklinikum Leipzig, AöR, Liebigstraße 22, 04103, Leipzig, Deutschland

    M. Pierer & C. Baerwald

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  1. M. Pierer
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  2. C. Baerwald
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Correspondence to M. Pierer.

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Pierer, M., Baerwald, C. Biologikatherapie bei rheumatologischen Erkrankungen. Internist 49, 938–946 (2008). https://doi.org/10.1007/s00108-008-2059-2

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