Soedarsono Department of Pulmonology and Respiratory Medicine Faculty of Medicine, Universitas Airlangga Dr. Soetomo General Hospital

MDR-TB is a public health crisis 480 000 people developed MDR-TB in 2014 and 190 000 people died as a result of it. Patients with RR or MDR-TB are treated with a different combination of 2 nd -line drugs, usually for 18 months or more. Recently, a standardized treatment regimen lasting less than 12 months has been used in a number of countries Indonesia is one of the next countries

Conventional (WHO) regimen At least 18 months Individualized or standardized Most commonly used Shorter regimen 9-12 months Standardized New recommendation by WHO in 2016 to provide to select patients New recommendation by WHO in 2016 to provide to select patients

WHO updated its treatment guidelines for drug-resistant TB in May 2016 and included a recommendation on the use of the shorter MDR-TB regimen under specific conditions.

Bangladesh regimen : 2014 follow-up included 515 patients 84% treatment success 95% of patients completed treatment within 12 months High-level FQ resistance predictor for unfavorable outcome, especially when also PZA resistant 75 patients from Niger1 and 150 from Cameroon treated for 12 months: success in 89% Aung et al. IJTLD 2014

Standardized shorter MDR-TB regimen with seven drugs and a treatment duration of 9-12 months Indicated conditionally in MDR-TB or RR-TB, regardless of patient age or HIV status Lowered costs (<US$1,000 in drug costs/patient) and reduced patient loss expected

Rifampicin-resistant TB (RR-TB) is caused by TB bacteria that are resistant to at least rifampicin, one of the most effective anti-tb medicines. Multidrug-resistant TB (MDR-TB) is caused by TB bacteria that are resistant to at least isoniazid and rifampicin, the two most effective anti-tb drugs. Extensively drug-resistant TB (XDR-TB) is a form of MDR-TB that is also resistant to any fluoroquinolone and any of the second line anti- TB injectable agents (i.e. amikacin, kanamycin or capreomycin).

4-6 Km-Mfx-Pto-Cfz-Z-Hhigh-dose-E / 5 Mfx-Cfz-Z-E Km=Kanamycin; Mfx=Moxifloxacin; Pto=Prothionamide; Cfz=Clofazimine; Z=Pyrazinamide; Hhigh-dose= high-dose Isoniazid; E=Ethambutol 2016 WHO Treatment Guidelines

+ for adults over 59 years of age, the dose will be reduced to 10 mg/kg (max dose 750 mg) Gatifloxacin is currently unavailable in most countries 2016 WHO Treatment Guidelines

About 580,000 new cases of RR-TB or MDR- TB emerge each year globally Patients with MDR-TB are typically treated with more medicines and for much longer (conventionally 20 months or more) A fairly standardised treatment regimen lasting 9-12 months has been reported to give relapse-free cure in >85% of selected MDR-TB patients,

This regimen is not recommended for patients with pre-xdr/ XDR TB 2016 WHO Treatment Guidelines

Treatment success versus all other outcomes of shorter regimen was reported in 84% (95%CLs: 79%- 87%) Vs MDR-TB patients treated with a variety of individualised regimens of longer duration had a pooled treatment success of 62% (95%CLs: 53%-70%)]. (Amongst patients who did not complete treatment successfully, 7% died, 6% were lost to follow up, and 3% had a treatment failure)

The shorter MDR-TB regimen can be used in people living with HIV, including those who are receiving antiretroviral treatment People living with HIV need to be given the same consideration for treatment with the shorter MDR-TB treatment regimen as people who are HIV seronegative There may a potential for overlapping, additive toxicities or for drug-drug interactions between some anti-retroviral medicines and the injectable medicines, moxifloxacin and clofazimine Close monitoring of people on the two regimens is advised given that the data in this area remains limited.

Shorter MDR-TB regimens have largely been used in patients older than 14 years of age The WHO recommendation is that the regimen can be used in children under 15 years. However, given the incomplete information about the safety profile of the regimen as a whole, close monitoring including adsm is recommended during its use in both children and adults.

Trans R Soc Trop Med Hyg 2016; 110: 163 172

All observational, prospective All included patients never exposed to second line drugs Bangladesh regimen : 9 months Clofazimine, high dose gatifloxacin, EMB, PZA throughout plusprothionamide, kanamycin, and high-dose INH for minimum of 4 months (intensive phase extended to smear conversion) Relapse free cure of 88% among 206 patients Van Deun et al. AJRCCM 2010

Lancet 2016; 387: 2486 87.

(Core drug) (Core drug) (Core drug) 2016 WHO Treatment Guidelines

Bdq+ 4 core SLDs + PZA intensive phase will be at least 8 months continuation phase will be at least 12 months Challenge TB Clinical and Programmatic Guide

The increased burden of MDR-TB represents a major threat to TB control A shorter, cheaper, and well-tolerated MDR- TB regimen is likely to impact the number of patients treated and improve adherence Indonesia is planning to use those shorter regimen for RR TB/MDR and is going to develop the implementation of the new drugs