Transcript American College of Rheumatology Guidelines for Screening

Delamanid for Multidrug-Resistant Pulmonary
Tuberculosis
Maria Tarcela Gler, M.D. et al.
N Engl J Med 2012;366:2151-60.
R2 Yang In-Ho/Prof. Park Myung Jae
Introduction
 Multidrug-resistant tuberculosis (MDR-TBc)
- TBc caused by M. tuberculosis that are resistant to
isoniazid and rifampin
- 440,000 cases of MDR-TBc occur anually (nearly 5%)
- requires combination therapy
- cure rates are lower and mortality is higher
Introduction
 Delamanid (OPC-67683)
- inhibits mycolic acid synthesis
- shown potent in vitro and in vivo activity against
drug-susceptible and drug-resistant M. tuberculosis
- in previous study of early bactericidal activity,
delamanid resulted in a decrease in the sputum M.
tuberculosis burden that was similar to that of rifampin
- controlled trial showing the predictive value of
sputum-culture conversion at 2 months for disease
relapse
Introduction
 Multinational, randomized, double-blind, placebo-
controlled trial
 Assess the safety, pharmacokinetic profile and
efficacy of delamanid in patients with sputum
culture-positive multidrug resistant tuberculosis
Methods
 Age 18-64
 Sputum-culture positive multidrug-resistant
tuberculosis
 Exclusion criteria
- Karnofsky PS <50
- HIV infection with CD4 cell count <350/mm3 or
receiving antiretroviral treatment
- Patients receiving antiarrhythmic agents or had
clinically relevant cardiovascular disease
- ECG findings of conduction abnormalities or QT
prolongation
Methods
 All patients were hospitalized during 8-week treatment
- intensive safety monitoring
- weekly sputum culture assessment
 Additional 4-week period of patient monitoring to
confirm the sputum culture status
 Two doses of delamanid(100mg twice or 200mg twice)
plus background drug regimen
vs
 Placebo plus standard drug regimen
RESULT
Conclusion
 Delamanid was associated with an increase in
sputum-culture conversion at 2 months among
patients with multidrug-resistant tuberculosis
could enhance treatment options for multidrugresistant tuberculosis.