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Empfehlungen für das Tuberkulose-Screening vor Gabe von TNF-α-Inhibitoren bei rheumatischen Erkrankungen

Recommendations for tuberculosis screening before initiation of TNF-α-inhibitor treatment in rheumatic diseases

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Zusammenfassung

Aufgrund des erhöhten Tuberkulose- (TB-) Risikos beim Einsatz von Tumor-Nekrose-Faktor- (TNF-)α-Inhibitoren in der Behandlung der rheumatoiden Arthritis und anderer Autoimmunkrankheiten sollte bei allen Patienten vor Anti-TNF-α-Therapie eine aktive Tuberkulose ausgeschlossen werden und ein Screening auf das Vorliegen einer latenten tuberkulösen Infektion (LTBI) erfolgen. Das Screening sollte eine Röntgenthoraxaufnahme, eine sorgfältige Anamnese und die Durchführung eines hochspezifischen Interferon-γ-Tests (IGRA) umfassen. (In Zukunft soll die bisherige Abrechenbarkeit der IGRA-Tests über Analogziffern durch eigene EBM-Ziffern abgelöst werden.) Da sowohl falsch-positive als auch falsch-negative Tuberkulin-Hauttest- (THT-) Ergebnisse in diesen Patientengruppen erwartet werden können, wird der früher durchgeführte THT nur noch in Ausnahmefällen empfohlen. Die Behandlung der LTBI umfasst in aller Regel eine Chemoprävention mit Isoniazid (INH) über 9 Monate.

Abstract

Due to the increased risk of tuberculosis (TB) under treatment with TNF-α inhibitors for rheumatoid arthritis and other autoimmune diseases, precautionary measures are required before initiating TNF-α-inhibitor therapy. Patients should have active TB ruled out and screening for latent TB infection should be performed. The screening should include chest X-ray, complete medical history, and the administration of a highly specific interferon-γ-release assay (IGRA). (In the future, the reimbursement of IGRA tests under an analogue procedure code is expected to be formalized by the application of a code specific to the TB-IGRA procedure.) As tuberculin skin test (TST) results can be expected to be either false-positive or false-negative in these patients, the TST, as commonly performed in the past, is recommended only in exceptional situations. For chemopreventive treatment of latent TB infection (LTBI), isoniazid is usually given for 9 months.

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Notes

  1. Ob und inwieweit sich die Rate nichtinterpretierbarer Testergebnisse zwischen den beiden IGRA-Verfahren signifikant unterscheidet, wird in weiteren Vergleichsstudien zu klären sein.

Abbreviations

BCG:

Bacille Calmette-Guérin

IFN-γ:

Interferon-Gamma

IGRA:

„Interferon-Gamma Release Assay“

LTBI:

Latente tuberkulöse Infektion

MTB:

Mycobacterium tuberculosis

NMT:

Nichttuberkulöse Mykobakterien (Umweltmykobakterien)

RA:

Rheumatoide Arthritis

TB:

Tuberkulose

THT:

Tuberkulin-Hauttest

TNF:

Tumor-Nekrose-Faktor

Literatur

  1. Ehlers S (2005) Why does tumor necrosis factor targeted therapy reactivate tuberculosis? J Rheumatol Suppl 74:35–39

    PubMed  CAS  Google Scholar 

  2. Wallis RS, Broder MS, Wong JY et al (2004) Granulomatous infectious diseases associated with tumor necrosis factor antagonists. Clin Infect Dis 38:1261–1265

    Article  PubMed  CAS  Google Scholar 

  3. Wolfe F, Michaud K, Anderson J, Urbansky K (2004) Tuberculosis infection in patients with rheumatoid arthritis and the effect of infliximab therapy. Arthritis Rheum 50:372–379

    Article  PubMed  CAS  Google Scholar 

  4. Keane J, Gershon S, Wise RP et al (2001) Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 345:1098–1104

    Article  PubMed  CAS  Google Scholar 

  5. Keane J (2005) TNF-blocking agents and tuberculosis: new drugs illuminate an old topic. Rheumatology (Oxford) 44:714–720

    Google Scholar 

  6. Schiff MH, Burmester GR, Kent JM, et al (2006) Safety analyses of adalimumab (Humira) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis. Ann Rheum Dis 65:889–894

    Article  PubMed  CAS  Google Scholar 

  7. Keane J, Breshinan B (2008) Tuberculosis reactivation during immunosuppressive therapy in rheumatic diseases: diagnostic and therapeutic strategies. Curr Opin Rheumatol 20:443–449

    Article  PubMed  CAS  Google Scholar 

  8. Paul-Ehrlich-Institut und Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose (2002). Empfehlungen zur Diagnose und Prävention der latenten Tuberkulose bei Patienten vor Beginn der Behandlung mit Remicade (Infliximab), zitiert in: Manger B, Michels H, Nüsslein HG, Schneider M, Sieper J und die Kommission Pharmakotherapie der Deutschen Gesellschaft für Rheumatologie. Neufassung der Empfehlungen der Deutschen Gesellschaft für Rheumatologie zur Therapie mit Tumornekrosefaktor-hemmenden Wirkstoffen bei entzündlichen Erkrankungen (Stand März 2006). http://www.dgrh.de/fileadmin/media/Qualitaetssicherung/Therapie-Empfeh-lungen/TNF-Blocker_06.pdf, letzter Zugang 12.12.2008

  9. Furst DE, Cush J, Kaufmann S et al (2006) Preliminary guidelines for diagnosing and treating tuberculosis in patients with rheumatoid arthritis in immunosuppressive trials or being treated with biological agents. Ann Rheum Dis 61:ii62–ii63

    Google Scholar 

  10. Tissot F, Zanetti G, Francioli P et al (2005) Influence of Bacille Calmette-Guérin vaccination on size of tuberculin skin test reaction: to what size? Clin Inf Dis 40:211–217

    Article  CAS  Google Scholar 

  11. Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose (2007) Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose. Pneumologie 58:657–665

    Google Scholar 

  12. Simon K, Gutland M (1988) Die Tuberkulinprobe in der Klinik – Dosierung und Wertung. Prax Klin Pneumol 42:423–426

    PubMed  CAS  Google Scholar 

  13. Symmons DP (2002) Epidemiology of rheumatoid arthritis: determinants of onset, persistence and outcome. Best Pract Clin Rheumatol 16:707–722

    Article  Google Scholar 

  14. Diel R, Nienhaus A, Loddenkemper R (2007) Cost-effectiveness of interferon-gamma release assay screening for latent tuberculosis infection treatment in Germany. Chest 131:1424–1434

    Article  PubMed  Google Scholar 

  15. Diel R, Ernst M, Döscher G et al (2006) Avoiding the effect of BCG vaccination in detecting Mycobacterium tuberculosis infection with a blood test. Eur Respir J 28:16–23

    Article  PubMed  CAS  Google Scholar 

  16. Diel R, Nienhaus A, Lange C et al (2006) Tuberculosis contact investigation with a new, specific blood test in a low-incidence population containing a high proportion of BCG-vaccinated persons. Respir Res 7:77

    Article  PubMed  CAS  Google Scholar 

  17. Matulis G, Jüni P, Villiger PM, Gadola SD (2008) Detection of latent tuberculosis in immunosuppressed patients with autoimmune diseases - performance of a Mycobacterium tuberculosis antigen specific IFN-gamma assay. Ann Rheum Dis 67:84–90

    Article  PubMed  CAS  Google Scholar 

  18. Diel R, Nienhaus A, Lange C, Schaberg T (2006) Cost-optimisation of screening for latent tuberculosis in close contacts. Eur Respir J 28:35–44

    Article  PubMed  CAS  Google Scholar 

  19. Piana F, Codecasa LR, Cavallerio P et al (2008) Use of a T-cell based test for detection of tuberculosis infection among immunocompromised patients. Eur Respir J 28:31–34

    Article  Google Scholar 

  20. Horsburgh CR (2004) Priorities for the treatment of latent tuberculosis infection in the United States. New Engl J Med 350:2060–2067

    Article  PubMed  CAS  Google Scholar 

  21. Diel R, Loddenkemper R, Meywald-Walter K et al (2008) Predictive value of a whole-blood IFN-y assay for the development of active TB disease after recent infection with M. tuberculosis. Am J Respir Crit Care Med 177:1164–1170

    Article  PubMed  Google Scholar 

  22. Panayi G, Corrigall V, Pitzalis C (2001) Pathogenesis of rheumatoid arthritis. The role of T cells and others beasts. Rheum Dis Clin North Am 27:1–18

    Article  Google Scholar 

  23. Mow WS, Abreu-Martin MT, Papadakis KA et al (2004) High incidence of anergy in inflammatory bowel disease patients limits the usefulness of PPD screening before infliximab therapy. Clin Gastroenterol Hepatol 2:309–313

    Article  PubMed  Google Scholar 

  24. Malipeddi AS, Rajendran R, Kallarackal G (2007) Disseminated tuberculosis after anti-TNFα treatment. Lancet 369:162

    Article  PubMed  Google Scholar 

  25. Efthimiou P, Sood S (2007) Quantiferon TB gold test: The new standard for screening of latent tuberculosis in patients with rheumatoid arthritis? Ann Rheum Dis 66:276

    Article  PubMed  Google Scholar 

  26. Raval A, Akhavan-Toyserkani G, Brinker A, Avigan M (2007) Brief communication: characteristics of spontaneous cases of tuberculosis associated with Infliximab. Ann Intern Med 147:699–702

    PubMed  Google Scholar 

  27. Ponce de Leon D, Acevedo-Vasquez E, Alvizuri S et al (2005) Attenuated response to purified protein derivative in patients with rheumatoid arthritis: study in a population with a high prevalence of tuberculosis. Ann Rheum Dis 64:1360–1361

    Article  CAS  Google Scholar 

  28. Vassilopoulos D, Stamoulis N, Hadziyannis E, Archimandritis A (2008) Usefulness of enzyme-linked immunospot assay (Elispot) compared to tuberculin skin testing for latent tuberculosis screening in rheumatic patients scheduled for anti-tumor necrosis factor treatment. J Rheumatol 35:1271–1276

    PubMed  Google Scholar 

  29. Sellam J, Hamdi H, Roy C et al (2007) Comparison of in vitro-specific blood tests with tuberculin skin test for diagnosis of latent tuberculosis before anti-TNF therapy. Ann Rheum Dis 66:1610–1615

    Article  PubMed  Google Scholar 

  30. Bartalesi F, Vicidomini S, Goletti D et.al (2008) QuantiFERON-TB Gold and TST are both useful for latent TB screening in autoimmune diseases. Eur Respir J 33:586–593

    Article  PubMed  Google Scholar 

  31. Greenberg JD, Reddy SM, Schloss SG et al (2008) Comparison of an in vitro tuberculosis interferon-gamma assay with delayed-type hypersensitivity testing for detection of latent mycobacterium tuberculosis: A Pilot Study in Rheumatoid Arthritis. J Rheumatol 35:770–775

    PubMed  Google Scholar 

  32. Gómez-Rheino JJ, Carmona L, Descalzo MÁ (2007) Risk of tuberculosis in patients treated with tumor necrosis factor antagonists due to incomplete prevention of reactivation of latent infection. Arthritis Rheum 57:756–761

    Article  CAS  Google Scholar 

  33. Gardam MA, Keystone EC, Menzies R et al (2003) Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis 3:148–155

    Article  PubMed  CAS  Google Scholar 

  34. Beglinger C, Dudler J, Mottet C et al (2007) Screening for tuberculosis infection before initiation of anti-TNF-α therapy. Swiss Med Wkly 137:621–622

    Google Scholar 

  35. Arend S, Leyten EM, Franken WP et al (2007) A patient with de novo tuberculosis during anti-tumor necrosis factor therapy illustrating diagnostic pitfalls and paradoxical response to treatment. Clin Infect Dis 45:1470–1475

    Article  PubMed  CAS  Google Scholar 

  36. Jeong YJ, Lee KS (2008) Pulmonary tuberculosis: Up-to-date imaging and management. Am J Roentgenol 191:834–844

    Article  Google Scholar 

  37. Theis VS, Rhodes JM (2007) Review article: minimizing tuberculosis during anti-tumour necrosis factor-alpha treatment of inflammatory bowel disease. Aliment Pharmacol Ther 27:19–30

    Article  PubMed  CAS  Google Scholar 

  38. Carmona L, Gómez-Reino JJ, Rodríguez-Valverde V et al (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 

  39. Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose (2004) Latente tuberkulöse Infektion: Empfehlungen zur präventiven Therapie bei Erwachsenen in Deutschland. Pneumologie 58:255–270

    Article  Google Scholar 

  40. Reichman LB, Lardizabal A, Hayden CH (2004) Considering the role of four months of rifampin in the treatment of latent tuberculosis infection. Am J Crit Care Med 170:832–835

    Article  Google Scholar 

  41. Sichletidis L, Settas L, Spyratos D et al (2006) Tuberculosis in patients receiving anti-TNF agents despite chemoprophylaxis. Int J Tuberc Lung Dis 10:1127–1132

    PubMed  CAS  Google Scholar 

  42. Ledingham J, Deighton C (2005) On behalf of the British Society for Rheumatology standards, Guidelines and Audit Working Group (SGAWG). Guidelines. Update on the British Society for Rheumatology guidelines for prescribing TNFα blockers in adults with rheumatoid arthritis (update of previous guidelines of April 2001). Rheumatology (Oxford) 44:157–163

    Google Scholar 

  43. Dixon WG, Hyrich KL, Watson KD, Lunt M (2008) BSRBR Control Centre Consortium, Symmons DPM, on behalf of the BSR Biologics Register and Epidemiology Unit, University of Manchester, Manchester, United Kingdom. EULAR 2008 [THU0134]. Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: Results form the BSR Biologics Register (BSRBR). Ann Rheum Dis 67 (Suppl II):178

    Google Scholar 

  44. Centers for Disease Control and Prevention (2004) Tuberculosis associated with blocking agents against tumor necrosis factor-alpha – California, 2002–2003. Morb Mortal Wkly Rep 53:683–686

    Google Scholar 

  45. Dosanjh DP, Hinks TS, Innes JA et al (2008) Improved diagnostic evaluation of suspected tuberculosis. Ann Intern Med 148:325–336

    PubMed  Google Scholar 

  46. Whittaker E, Gordon A, Kampmann B (2008) Is IP-10 a better biomarker for active and latent tuberculosis in children than IFNgamma? PLoS ONE 3:e3901

    Article  PubMed  CAS  Google Scholar 

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Interessenkonflikt

Der korrespondierende Autor weist auf folgenden Beziehungen hin: R. Diel hat Vortragshonorare von folgenden Firmen erhalten: Astra Zeneca, Biomerieux, Cellestis Europe, Oxford Immunotec, Sanofi Pasteur MSD. B. Manger gibt Beziehungen zu Abbott (Beratertätigkeit, Vorträge), Wyeth (Beratertätigkeit, Vorträge) und Essex (Beratertätigkeit, Vorträge) an. K. Krüger erhielt Vortragshonorare von den Firmen Abbott, Essex, Roche und Wyeth. Trotz des möglichen Interessenkonflikts ist der Beitrag unabhängig und produktneutral.

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Authors and Affiliations

  1. Lungenklinik Heckeshorn, HELIOS Klinikum Emil von Behring, Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose , Walterhöferstr. 11, 14165, Berlin, Deutschland

    R. Diel, B. Hauer &  R. Loddenkemper

  2. Kommission Pharmakotherapie der Deutschen Gesellschaft für Rheumatologie, Berlin, Deutschland

    B. Manger & K. Krüger

  3. Weiterbildungsstudiengang Public Health, Universitätsklinikum der Heinrich-Heine-Universität, Düsseldorf, Deutschland

    R. Diel

  4. Medizinische Klinik III, Universität Erlangen-Nürnberg, Erlangen, Deutschland

    B. Manger

  5. Rheumatologisches Praxiszentrum St. Bonifatius, München, Deutschland

    K. Krüger

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  1. R. Diel
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Correspondence to R. Loddenkemper.

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Diel, R., Hauer, B., Loddenkemper, R. et al. Empfehlungen für das Tuberkulose-Screening vor Gabe von TNF-α-Inhibitoren bei rheumatischen Erkrankungen. Z. Rheumatol. 68, 411–416 (2009). https://doi.org/10.1007/s00393-009-0475-x

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