Screening of Latent Tuberculosis before treatment with TNF blockers Ori Elkayam M.D Tel Aviv...
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Transcript of Screening of Latent Tuberculosis before treatment with TNF blockers Ori Elkayam M.D Tel Aviv...
Screening of Latent Tuberculosis before treatment with TNF
blockersOri 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 :
• 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
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 ?
Criteria for Tuberculin positivity 5 mm ≤ 10 mm ≤15 mm ≤
HIV positiveRecent immigrants
No risk factor for TB
TB on chest X raysJail residents, health workers
Organ transplants Immunosuppressed*
Silicosis, DM, CRF, malignancies
Children <4
< *15 mg Prednisone for at least 1 month or TNF blockers
Immunocompromised patients
• Treated with Prednisone
• Treatments with MTX, Imuran
• Further studies are needed
• Prone to infections and malignancies
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?
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
9
RA1301a
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
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
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
Spanish Society of Rheumatology Recommendations
TST<5 mm
Re-test
<5 mm
Chest X ray
Suggestive
≥5 mm
≥5 mm
Normal Contact
INH 9 months
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
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
“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
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
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
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
Guidelines (Europe)
• Greece Guidelines: Abnormal X ray
TST≥10
• French Guidelines: Abnormal X ray
History
TST≤10 mm
Guidelines (Europe)
• Swiss Guidelines:TST not recommended
History of exposure
Country of Origin
Interferon Gamma assays
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
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
PPD in different rheumatic diseases
NAgeSteroid (%)PPD+(%)PPD
RA945650304.5±7
SLE213848192.9±6.2
AS44364.5669.8±8
OA275115637.8±6.7
Incidence of MTB in Infliximab treated pts
• 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
Prevalence of TB in Israel (100000)
0
2
4
6
8
10
12
שנת דווח
Dept. of TB & AIDS, MOH, Jerusalem
#
Topics of discussion
• Milestones of TB in anti-TNF therapy Era• Guidelines for screening of latent TB before anti-TNF therapy
• Prevalence of TB in Israel
• HIV, TNF blockers and TB
• PPD in different rheumatic diseases
• Adverse consequences of over diagnosis of LTB
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
Incidence of MTB in Infliximab treated pts vs HIV+
• 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
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
Topics of discussion
• Milestones of TB in anti-TNF therapy Era• Guidelines for screening of latent TB before anti-TNF therapy
• Prevalence of TB in Israel
• HIV, TNF blockers and TB
• PPD in different rheumatic diseases
• Adverse consequences of over diagnosis of LTB
Adverse consequences of over diagnosis and treatment LTB
• Drug toxicity • Hepatotoxicity
• Drug multi resistance
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.
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
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