latent tuberculosis simplifying the clinical approach to a … tb... · 2016-10-04 · simplifying...

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


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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


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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


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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”


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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


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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


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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


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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


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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



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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


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


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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

latent tuberculosis simplifying the clinical approach to a … tb... · 2016-10-04 · simplifying...

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