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Screening of Latent Tuberculosis before treatment with TNF  blockers PowerPoint PPT Presentation


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Screening of Latent Tuberculosis before treatment with TNF  blockers. Ori Elkayam M.D Tel Aviv Medical Center. Guidelines of the Israeli association of Rheumatology for the prevention of tuberculosis in patients treated with TNF-alpha blocker. Screening includes :

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Screening of Latent Tuberculosis before treatment with TNF  blockers

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Screening of latent tuberculosis before treatment with tnf blockers l.jpg

Screening of Latent Tuberculosis before treatment with TNF  blockers

Ori Elkayam M.D

Tel Aviv Medical Center


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Guidelines of the Israeli association of Rheumatology for the prevention of tuberculosis in patients treated with TNF-alpha blocker

  • Screening includes :

  • Tuberculin Skin Test (TST)

  • Chest X-ray

  • Questionnaire about possible exposure to TB

Elkayam O, Balbir-Gurman A, Lidgi M, Rahav G, Weiler-Ravel D


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Risk Factor Questionnaire

  • Did you immigrate from a country with high TB prevalence ?

  • Have you ever been in close contact with TB?

  • Have you been offered to be treated for TB ?


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Criteria for Tuberculin positivity

* >15 mg Prednisone for at least 1 monthor TNF blockers


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Immunocompromised patients

  • Treated with Prednisone

  • Treatments with MTX, Imuran

  • Further studies are needed

  • Prone to infections and malignancies


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Debate

  • Should TST≥5 mm considered positive for all candidates to anti-TNF therapy ?

  • Is the diagnosis of latent TB similar for RA patients, PsA and AS?


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Topics of discussion

  • Milestones of TB in anti-TNFα therapy Era

  • Guidelines for screening of latent TB before anti-TNF therapy

  • PPD in different rheumatic diseases

  • Prevalence of TB in Israel

  • HIV, TNF  blockers and TB

  • Adverse consequences of over diagnosis of LTB


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Tuberculosis and TNF alpha blockers

  • 70 patients reported to the FDA, including from states with low incidence of TB

  • Extrapulmonary manifestations in 40 pts

  • Fatalities

  • Patients should be evaluated for latent tuberculosis infection with a tuberculin skin test.

Keane et al, NEJM 2001;345:1098-104

RA1301a


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BIOBADASER

  • Treatment of RA with TNF inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report. A&R2003

  • Effectiveness of recommendations to prevent reactivation of LTB in patients treated with TNF antagonists.A&R 2005

  • Risk of tuberculosis in patients treated with tumor necrosis factor antagonists due to incomplete prevention of reactivation of latent infection. A&R2007


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BIOBADASER (1)

  • Registry based on the voluntary participation of hospital and community-based rheumatology Units

  • 1540 pts : 1265 RA, 89 PsA, 76 AS

  • 17 pts with TB; 65% extra-pulm, 2 deaths

  • 6 pts: PPD and X rays missing

  • 5 pts:prior X evidence of TB

  • Incidence :1100/100000

A&R2003


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Spanish Society of Rheumatology

Recommendations

TST

<5 mm

≥5 mm

Re-test

<5 mm

≥5 mm

Chest X ray

Contact

Normal

INH 9 months

Suggestive


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BIOBADASER (2)

  • March 2002: data collected using standard forms

  • Since then, data reported by an electronic system.

  • Audit : 18% of the data reported are incomplete

  • 34 TB ( 28 RA)ׁ

  • 32 before March 2002

  • 2 pts after 03/02 fulfilled criteria for LTB

  • Decrease of >70 % in rate of TB

A&R 2005


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BIOBADASER (3)

  • Following March 2002, 5,198 registered .

  • 15 ATB cases were noted (rate 172 per 100,000 patient-years).

  • Recommendations fully followed in 2,655 treatments.

  • Probability of ATB was 7 times higher when recommendations were not followed .

  • Two-step tuberculosis skin test for LTBI was the major failure in complying with recommendations.

R2007&A


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“The recommendation that TST≥5 mm should be an indication for INH was established because of the high TB risk detected in this population. In populations with lower background rates , other strategies may be proposed “

Gomez-Reino et al


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Topics of discussion

  • Milestones of TB in anti-TNFα therapy Era

  • Guidelines for screening of latent TB before anti-TNF therapy

  • PPD in different rheumatic diseases

  • Prevalence of TB in Israel

  • HIV, TNF  blockers and TB

  • Adverse consequences of over diagnosis of LTB


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Guidelines (USA)

  • Gardam (2003) :

    TST :0-4 : Major immune suppression +risk factors

    5-9 : Epidemiologic risk factors ( Foreign born

    occupational, abnormal chest X ray, known contact)

    10 : all others

  • Winthrop (2005):

    Refer To CDC definitions of LTB

  • Furst D :

    CDC recommendations


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Guidelines (Europe)

British Thoracic Society :

-Immunosuppressive therapy

No value of TST in pts

Risk stratification /Chest X ray

- No immunosuppressant therapy :

TST ≥15 for BCG +

TST ≥5 for BCG +

Risk stratification


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Guidelines (Europe)

  • Greece Guidelines: Abnormal X ray

    TST≥10

  • French Guidelines: Abnormal X ray

    History

    TST≤10 mm


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Guidelines (Europe)

  • Swiss Guidelines:TST not recommended

    History of exposure

    Country of Origin

    Interferon Gamma assays


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Topics of discussion

  • Milestones of TB in anti-TNFα therapy Era

  • Guidelines for screening of latent TB before anti-TNF therapy

  • PPD in different rheumatic diseases

  • Prevalence of TB in Israel

  • HIV, TNF  blockers and TB

  • Adverse consequences of over diagnosis of LTB


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Attenuated response to PPD in RA

  • 112 RA patients vs 96 healthy controls

  • Similar background : age, sex, BCG vaccine

  • Median PPD : 4.5 in RA vs 11.5 in healthy

  • Negative PPD : 70% in RA vs 26% in healthy


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PPD in different rheumatic diseases


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Infliximab treated :

-USA : 50/100000

-EU :152/100000

-Spain:1100/100000

-Sweden :100/100000

Rate of TB in RA

-USA : 6.2/100000

-Spain : 90/100000

-Sweden: 10/100000

Incidence of MTB in Infliximab treated pts


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Prevalence of TB in Israel (100000)

#

Dept. of TB & AIDS, MOH, Jerusalem


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Topics of discussion

  • Milestones of TB in anti-TNF therapy Era

  • Guidelines for screening of latent TB before anti-TNF therapy

  • PPD in different rheumatic diseases

  • Prevalence of TB in Israel

  • HIV, TNF  blockers and TB

  • Adverse consequences of over diagnosis of LTB


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TNF  Blockers, HIV and TB

  • High frequency of extra-pulmonary manifestations

  • HIV impairs TNF mediated MG apoptotic response to MT

  • HIV + with TST≥5 mm are treated for LTB , independently of CD4 levels


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Infliximab treated :

-USA : 50/100000

-EU :152/100000

-Spain:1100/100000

-Sweden :100/100000

HIV +

- South –Africa : 2.2/100

-Swiss : 1.6/100

20 ≤fold increase of reactivation

Incidence of MTB in Infliximab treated pts vs HIV +

Rate of TB in RA pts in USA : 6.2/100000

Rate of TB in RA pts in Sweden :10/100000

Rate of TB in RA pts in Spain : 90/100000


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Topics of discussion

  • Milestones of TB in anti-TNF therapy Era

  • Guidelines for screening of latent TB before anti-TNF therapy

  • PPD in different rheumatic diseases

  • Prevalence of TB in Israel

  • HIV, TNF  blockers and TB

  • Adverse consequences of over diagnosis of LTB


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Adverse consequences of over diagnosis and treatment LTB

  • Drug toxicity

  • Hepatotoxicity

  • Drug multi resistance


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Multi drug resistance in Southern Israel

  • Overall INH resistance rate :16%

  • In former soviet union :INH resistance of 32%

  • Resistance to any drug observed in 29% overall and 50% of isolates among IFSU.

  • Multi drug-resistant tuberculosis was observed in 8.5% and 17%, respectively.


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Conclusions

  • Guidelines of diagnosis of LTB should take into consideration :

  • The prevalence of TB in the country

  • The immunosuppressive state of the patients

  • Adverse consequences of over diagnosis of latent TB


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Conclusions

  • In RA patients :TST≥5 mm

  • In PsA and AS not treated with immunosuppressive drugs : TST ≥10 mm

  • Risk stratification and X chest ray


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