b) Latency - It is crucial to determine the latency status pre use of biologic therapy.
Data suggests that in immuno-compromised patients, treatment with prophylaxis can reduce TB by 70% when patients are compliant.
Definition and diagnosis of the LATENT state. This implies treatment is essential
i) Assessment of Lantency
(a) Mantoux (TST) - the most essential component
Induration > 5mm = positive (induration.) =and implies latent TB.
All new patients to be tested BEFORE anti TNF Rx
or any other biologic therapy
In paediatrics -If at baseline a negative test is recorded, then we advise retest every 12 months, as this tests for exposure.
In adults no data is available re retest.
(b) CXR - The main role is
to exclude active disease.
(c) Quantiferon-TB (QFT)
No cross reactivity in previously BCG Vaccinated patients
QFT results may be confirmed with TST
Must be conducted simultaneously to, or prior to TST
Although QFT is not recommended for confirmation of TST results, QFT can be used for surveillance <12 months after a negative TST, if the initial QFT is negative
Not indicated where active TB is suspected
ii) Treatment choice for latency:
(a) INH - RIF combined - The benefit may last longer - in HIV patients, benefit is observed for up to 3 years.
(b) INH alone - protected for 1 year in HIV patients.CDC guidelines - Advise INH at least 6 months minimum 9 months desirable.
Combination Rifampicin - INH for 3 months, is advised in certain circumstances only. This applies where early initiation of therapy considered absolutely vital i.e. with aggressive disease.
(c) Duration of treatment.See clause (a) and (b).
(d) Time to start anti-TNF after latency treatment started
Information limited. No data available
recommend full treatment but practitioner judgement allowed vs. activity of disease
INH - RIF regimen may be more useful here as shorter regimen.
(e) Monitoring of prophylaxis treatment.
Concerns regarding treatment of latent status
Hepatotoxicity - more significant in methotrexate co therapy. Drug resistance - not considered a problem if TB Rx becomes required.
(i) Liver function testing
1. ALT at baseline. Minimum testing - MONTHLY if baseline abnormal. 1% of INH patients will get increase in enzymes. Monitor Levels of ALT
a. If >3 x with symptoms - stop
b. If > 5 times without symptoms - stop.
2. Education of patient regarding symptoms to suggest toxicity - i.e. nausea, vomiting, upper quadrant pain, dark urine..etc.
iii) Repetition of screening program
(a) There is no evidence in adults of benefit to rescreening the MANTOUX -.
c) Active disease
i) Must exclude in all case..... as there is absolute contraindication to TNF Rx.
ii) To determine if active TB is present
(a) If there is a history of previously treated TB - ensure no active disease. Anti TNF Rx is allowed if the patient had > 6 months of full therapy, or the disease was in the distant / remote past. Role for empirical latency treatment in these cases is unclear as there is no data available.
(b) Diagnosis of active disease:CXR: If abnormal.
Symptoms: Cough > 2 weeks
Sputa if obtainable - plus culture (4 weeks.)
iii) Treatment in disease whilst on TNF.
(a) Diagnosis and Treatment in Patients with TNF drug Rx in situ.Vigilance.
Beware of atypical disease / presentation.
Unusual histology - poor granuloma formation.
STOP TNF drug.
No reintroduction until TB therapy completed.