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TRANSCRIPT
Belknap: Latent Tuberculosis: simplifying the clinical approach
02/24/2016
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Latent Tuberculosis: simplifying the clinical approach to a
complex biologic disease
Bob Belknap M.D.
Director, Denver Metro TB Program
President, National TB Controllers Association
I have no conflicts of interest
Objectives After the talk, participants will be able to describe: 1. the steps for deciding whether to
recommend LTBI treatment to a patient 2. the advantages and challenges with
current shorter-course treatment regimens for LTBI
Belknap: Latent Tuberculosis: simplifying the clinical approach
02/24/2016
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Case 1 - 77 y/o female
• Born in Colorado - cousin with TB when she was young
• Rheumatoid arthritis on methotrexate and plaquenil
• TST of 17mm at age 62 (not treated) • QFT (+) now
Should she be treated for LTBI?
Objectives 1. the steps for deciding whether to
recommend LTBI treatment to a patient • Is the person infected with TB?
• Any evidence for active disease?
• Do the benefits of treatment
outweigh the risks?
Case 1 - 77 y/o female
Infected – YES Active Disease – NO Risks / Benefits n RA is well controlled. No plans for TNF-blocker or other biologic n On oxycontin and hydrocodone for chronic pain
Belknap: Latent Tuberculosis: simplifying the clinical approach
02/24/2016
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Risks / Benefits: www.tstin3d.com
Risks / Benefits: www.tstin3d.com
IGRA vs TST: Ability to predict future TB
Meta-analysis q commercial and in-house assays q Median follow-up 4years (IQR 2-6)
Results q Incidence in IGRA (+) was 4-48/ 1,000 person-yrs q Incidence Rate Ratio for test (+) vs test (-)
IGRAs 2.11 [95% CI 1.29-3.46] TST 1.60 [0.94-2.72]
Rangaka, Lancet ID Jan 2012 12: 45
Belknap: Latent Tuberculosis: simplifying the clinical approach
02/24/2016
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IGRA versus TST Prior to Golimumab
QFT + 71
(9.1%)
TST + 119
(15.2%)
TST + 62
(5.0%)
QFT + 72
(5.8%) 28 24
BCG vaccinated Non BCG vaccinated
2282 patients underwent screening prior to golimumab therapy with QFT-GIT and TST
Hsia EC, et al. Arthritis and Rheum 2012;64:2068
Operational Considerations: IGRA vs TST
Advantages
• One visit • Less subjective • Better in BCG-
vaccinated • Results reported
electronically Ø Retrievable Ø Easier to analyze
epidemiologic data
Disadvantages
• Need to register • Lab restrictions on
time and # of tests • Takes more time to
draw blood • Greater risk of
vasovagal syncope • Higher material
costs
Case 2 - 20 y/o student
• Born in India • Required to get TB testing for college
enrollment • TST = 11 mm CXR = normal
“It’s due to my BCG” • QFT positive (TB-nil = 1.15)
“It’s boosting from the TST” • Repeat QFT negative (TB-nil = 0.34)
“Finally we agree”
Belknap: Latent Tuberculosis: simplifying the clinical approach
02/24/2016
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2 Simple Rules When Ordering Tests
1. Have a plan for all possible results when you order a test
2. Don’t get a test if the result isn’t going to
change your management
So you’ve decided someone has TB infection…
n Rule out active TB Ø CXR on everyone Ø sputum collection if the CXR is abnormal or the
person is symptomatic
n Determine prior history of treatment for LTBI or TB disease
n Assess risks of toxicity n Determine current and previous drug therapy
Belknap: Latent Tuberculosis: simplifying the clinical approach
02/24/2016
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Benefit of LTBI Treatment
IUAT 1968 41: 159-171
Benefit of LTBI Treatment
IUAT 1968 41: 159-171
1985-1995 1996-2006
Smith County, TX Cegielski, AJPH 2013; 13(7): 1292
Belknap: Latent Tuberculosis: simplifying the clinical approach
02/24/2016
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Poor completion with INH
Hirsch-Moverman IJTLD 19(1): 31
Rifampin vs INH Treatment completion
q 78% Rifampin vs 60% INH Grade 3/4 adverse events
q 7/418 (1.7%) vs. 17 / 422 (4.0%) INH
Menzies Ann Int Med 2008; 149:689
Effectiveness of Contact Investigations
• 128 (34%) of active TB prevented
• 248 (66%) more – missed opportunity
MMWR Jan 2016
Belknap: Latent Tuberculosis: simplifying the clinical approach
02/24/2016
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Prevent TB – TBTC Study 26
Treatment Completion: 82% with 3HP 69% with 9H
Sterling NEJM December 2011
TBTC iAdhere: results
CROI 2015; Manuscript in development
Flu-like and other Systemic Drug Reactions with 3HP
• INH 15/ 3659 (0.4%) • 3HP 138/3893 (3.5%) (p< 0.001)
• 87 flu-like syndrome • 23 rash • 13 severe reaction • 6 hypotension
Sterling CID August 2015
Belknap: Latent Tuberculosis: simplifying the clinical approach
02/24/2016
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Rifamycins and Drug-interactions
Case 3 – 43 y/o female with RA
n Born in MX n BCG-vaccinated n Meds:
q Methotrexate q Prednisone 5 mg
n TST 23 mm (by report) n QFT negative
Risks / Benefits: www.tstin3d.com
Belknap: Latent Tuberculosis: simplifying the clinical approach
02/24/2016
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Case 3 – 43 y/o with RA
Repeated the TST 27mm
Risk for infection Risk for progression Recommended latent TB treatment • Patient didn’t tolerate INH; didn’t start a TNF-α • 2 years later, a repeat QFT (+), treated successfully with rifampin
Risks / Benefits: www.tstin3d.com
Objectives 1. the steps for deciding whether to
recommend LTBI treatment to a patient • Test people at risk for infection • Have a plan before your order a test (TST
or IGRA) – make a decision • Evaluate the risks and benefits “a decision to test is a decision to think”
John Bernardo
Belknap: Latent Tuberculosis: simplifying the clinical approach
02/24/2016
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Objectives 2. the advantages and challenges with
shorter-course treatment regimens • Higher completion with short-course
therapy (? higher treatment acceptance) • Drug-drug interactions (usually
manageable) • Systemic drug reactions are more
common with rifamycins but generally mild