Anti-TNF medication and tuberculosis

Transcription

1 Anti-TNF medication and tuberculosis Marleen Bakker Amsterdam

2 Contents Why? Who? How? How? testing + interpretation - 2 treatment

3 Why? Blocking TNF has major effect on immune-mediated inflammatory diseases (IMIDs)! results in increased risk of Mycobacterial infections (Mtb 25x)

4 Who? IMID patients: RA, IBD (Crohn, CU), psoriasis, Bechterew,.. Who ar candidate for use of TNFα inhibitors: Infliximab Remicade Etanercept Enbrel Adalimumab Humira Certolizumab Cimzia Golimumab Simponi

5 Miss D Born in Cabo Verde 2010 uveïtis 2010 M Crohn: immunosuppression, no benefit 2012 Planned to start Adalimumab what do you do?

6 How? 1 Select those pre-antitnf who are at risk for reactivation TB 1A Exclude / diagnose and treat active TB 2 Start treatment latent TB pre start antitnf

7 How - guidelines Diversity of guidelines/statements within Europe TBNET consensus Statement Eur Resp J 2010;36: Dutch Statement Tuberculose en TNF-α blokkerende therapie

8 How testing? - History taking, including results of former TB tests/exposure - Chest x-ray - TST/IGRAs - NB Those tested often are under immunosuppression: radiology and TB tests can be false-negative; negative tests do not exclude TB (infection) - Any positive result is reason to consider latent TB treatment after excluding active TB

9 Guidelines - TBNET Statement: - TST alone not sensitive/specific enough - Too little data in pre-antitnf group to advise IGRA alone - TST in non BCG-vaccinated (10 mm) + IGRA - European: TST IGRA TST and IGRA +/- boosting - Dutch guideline: TST (10 mm; immunosuppressed: 5 mm) and IGRA

10 Miss D Born in Cabo Verde - Adalimumab - Chest x-ray (N); - No latent tb test because of BCG (?) - Advised to seek help in case of complaints - X-ray: test for active TB - history + epidemiology: LTBI - TST and IGRA

11 Miss D - History + epidemiology.. - How? - When start adalimumab?

12 Guidelines - TBNET Statement: 9-12H - 3HR - European: 2RZ(!) 3R 4R 6H 9H 12H 3HR 4HR - Dutch guideline: 4HR - 9H 4R - When start anti-tnf: 4 wks (TBNET) 2 months (dutch) - No preventive treatment for M/XDR TB

13 Miss D Year after start adalimumab starts to cough (?) GP amoxicillin 2 weeks later: fever and night sweats Returns to GP: night sweats and fever and a friend (CV) with lung tb..gp: public health care will contact you So she waits.

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15 Miss D TB under anti-tnf 1-2% all TB (NTR)..can be hard to diagnose due to lack of clinical symtoms, lack of radiological signs and falsenegative test results. What do you do?

16 Guidelines Stop anti-tnf Start tb treatment immediately; maximal effort to achieve microbiology, molecular tests if possible European = TBNET = dutch Reactivation or (re)infection? Median time after start anti-tnf: 13 months clustered with her friend Kwon et al.: J Clin Rheum 2014;20(2):68-73

17 Miss D At 6 weeks TB treatment: Favorable clinical reaction, normal sensitivity strain Starts to complain about her eyes/crohn, wants to restart anti-tnf What do you advise?

18 Guidelines Preferably after completing TB treatment If no complete treatment: at least a favorable clinical reaction on TB treatment and confirmation of sensitive strain; perferably after intensive phase In life-threatening (neuro-)iris consider restart anti-tnf Clin Infect Dis 2008;47:e83-85

19 Miss D Restart adalimumab at 2 months, very happy even happier when TB treatment stopped at 6 months. Ongoing risk under anti-tnf treatment: - Reinfection - False-negative test results latent/active TB - Reactivation in spite of LTBI-treatment (sensitive/resistant strain)

20 Miss P Healthy law student, 24, dutch Weight loss 8 kg/6 weeks, fever, diarrhea, night sweats GP: appendicits hospital GE: extensive ulceration intestines / biopsy: granulomatous reaction M Crohn

21 Immunosuppression without benefit infliximab (TST negative) Further detoriation condition perforation ileum, extensive TB everywhere abdomen + chest. Weeks at ICU, hardly survived.

22 At 1 year: immense immune reconstitution inflammatory syndrome At 8 years (2014) after correction AP, aesthetic surgery abdomen, lymph node resections and giving birth to healthy daughter.. persistant pus in the liver (Aur+) Partner, 2 sisters and mother: active TB Tegen de Tuberculose 110(1):16-18, 2014

23 Miss P Exceptional case misdiagnosing tb for IMID, but not unique! Arend et al Clin Infect Dis 2007;45: Chest x-ray before start anti-tnf! TB under anti-tnf can go completely out of control testing & treating (L)TB to prevent (very nasty) TB!

24 What we still need. a test for viable Mycobacteria in LTBI optimal testing strategy = optimal selection of patients/optimal PP value for the development of TB under TNF blocking knowledge of optimal LTBI treatment pre anti-tnf (use anti-tnf to shorten LTBI treament??) and, last but not least: a test that differentiates latent from active TB

25 THM Anti-TNF treatment warrants testing and treating (L)TB pre-start. NB Potential risk of any (cellular) immunosuppressive condition! Ongoing risk under TNF-blocking treatment! Work up >> latente TB test: A/LO/X + Mx/IGRA, Diversity in testing and treating within Europe Inform your patient about TB/risks (travelling!). Inform GP! Primary prophylaxis after excluding active TB if exposure under anti-tnf

26 Literature - 1 Statement Tuberculose en TNF-α blokkerende therapie Solovic I, Sester M et al.: The risk of tuberculosis rlated to tumour necrosis factor antagonist therapies: a TBNET consensus statement. Eur Resp J 2010; Diel R et al.: Interferon-γ release assays for the diagnosis of latent Mycobacterium tuberculosis infection: a systematic review and metaanalysis. Eur Resp J 2011;37:88-99 Sester M et al.: Interferon-γ release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis. Eur Resp J 2011;37:

27 Literature - 2 Mack U et al.: LTBI: Latent tuberculosis infection or lasting immune response to M. tuberculosis? A TBNET Consensus Statement. Eur Resp J 20091;33: Smith MY et al.: Tuberculosis screening in prescribors of anti-tumor necrosis factor therapy in the Euroean Union Int J Tuberc Lung Dis 2012;16(9): Cantini et al.: Adalimumab, Etanercept, Infliximab, and the risk of tuberculosis: data from clinical trials, National Registries, and postmarketing surveillance. J Rheum 2014;91:47-55 Cantini et al.: Tuberculosis risk in patients treated with non-anti-tumor necrosis factor-α(tnf-α) Targeted Biologics and recently licensed TNF-α inhibitors: data from clinical trials and national registries. J Rheum Suppl 2014;91:56-64