Results from the endtb Project in Kazakhstan

Transcription

1 Tuberculosis in 2017: Searching for new solutions in the face of new challenges 6th TB Symposium Ministry of Health of the Republic of Belarus, Republican Scientific and Practical Center for Pulmonology and Tuberculosis, and Médecins Sans Frontières 1-2 March, 2017, MINSK, BELARUS Results from the endtb Project in Kazakhstan Askar Yedilbayev, MD, MPH Program Director for Russia and Kazakhstan Partners In Health

2 endtb Project in Kazakhstan In accordance with the National Complex Plan to Fight TB in Kazakhstan for , which was endorsed by Government Decree 597 of May 31, Articles 20 и 21: Phased introduction of individualized treatment regimens for M/XDR-TB based on results of DST; Memorandum of collaboration between MOH and Partners In Health of October 27, 2015.

3 Drug procurement 01/ / / /2017 ВСЕГО BDQ, 100 mg DLM, 50 mg LZD, 600 mg CFZ, 100 mg CFZ, 50 mg IMI/CLS, 500 mg Quality-assured drugs through GDF; Waiver mechanism from the NDRA of MOH; Forecasting based on latest WHO recommendations on duration of therapy of DR-TB; Other SLD procured by NTP.

4 Treatment sites Akmolinskaya oblast Astana NSCP Almaty oblast Almaty Туберкулез в 2017 году: поиск новых решений перед лицом новых вызовов Симпозиум по вопросам лечения туберкулеза Министерство здравоохранения Республики Беларусь, Республиканскии научно-практическии центр пульмонологии и фтизиатрии, "Врачи без границ"/ Médecins Sans Frontières

5 Program documents Program documents adjusted to Kazakhstan endtb clinical guide; adsm; Informed consent; Data collection on effectiveness and safety.

6 Eligibility criteria for treatment with new TB drugs Patients for whom the construction of a regimen with four likely effective second-line drugs is not possible: XDR; Pre-XDR (MDR-TB + FQ), (MDR+ 2 nd line injectable); RR/MDR-TB patients with two or more SLDs compromised; Contact with a patient infected with a strain with one of the above resistance patterns - a, b, c. 6

7 Eligibility criteria for treatment with new TB drugs Patients who have high risk of developing unfavorable outcome: Patients with extensive or advanced disease; Patients with increased likelihood of acquisition of additional resistance or other conditions; Patients from catchment areas that have poor MDR-TB treatment outcomes despite good programmatic conditions. 7

8 Eligibility criteria for treatment with new TB drugs Patients unable to tolerate MDR drugs necessary for construction of the regimen; Patients who "failed" an MDR regimen by WHO 2013 definitions. 8

9 Introduction of new TB drugs Total cohort of patients in endtb Project 573; Treatment started on February 17, 2016; End of enrollment expected on September 30, 2018; NFM GFATM grant 450 patients (summer 2017). Treatment site Enrollment as of 02/01/2017 Almaty city 35 Astana city 55 Almaty oblast (North) 1 Almaty oblast (South) 19 Akmolinskaya oblast 40 NSCP MOH 77 TOTAL 227

10 Cohort characteristics Clinical forms of TB N (%) TOTAL 227 Extrapulmonary TB 0 Bacteriologically confirmed TB 100% Bilateral disease 63.4% Infiltrative TB 122 (53.7%) Disseminated TB 5 (2.2%) Cavities 99 (43.7%) Caseous pneumonia 1 (0.4%)

11 Cohort characteristics Patient type (%) New 18.3% Relapse 29.4% Treatment after lost to follow up 4.9% Treatment failure 46.0 % Other previously treated cases 1.5% Previously treated cases with SLD 79.9%

12 Cohort characteristics Cohort characteristics (%) Age 36.4 лет (min 17 max 69) Male 61% HIV-infection 2.5% Hepatitis C 13.2% Hepatitis B 2.5% Diabetes mellitus 7.6% Low BMI (<18.5) 33.5%

13 Cohort characteristics Drug resistance profile 1.0% 4.0% 27.9% 47.7% 12.1% MDR Pre-XDR with FQ Pre-XDR with SLI XDR Clinical XDR Other 8.1%

14 Introduction of new TB drugs (227) Number of patients enrolled into endtb Project BDQ DLM BDQ+DLM

15 New TB drugs in treatment regimens* 120% 100% 100% 80% 71% 69% BDQ DLM 60% LZD 40% 37% 29% CFZ IMI/CLS 20% 0% * Cohort of 208 patients entered into the endtb EMR

16 New TB drugs in treatment regimens Treatment regimen N 227 BDQ-containing regimen 161 Extension of BDQ for another weeks 95 (59%) DLM-containing regimen* 88 Extension of DLM for another weeks 18 (20.5%) Concomitant use of BDQ-DLM** 23 Extension of BDQ-DLM for another 12 weeks 3 (13%) * Treatment started in June 2016 **Treatment started in August 2016

17 Culture conversion* NSCP Almaty city Astana city Akmolinskaya oblast Almaty oblast Total enrolled Culture positive at start of therapy After 1 month 34.5% 33.3% 66.6% 81.8% 60 % After 2 months After 3 months After 4 months After 5 months No conversion 65.5% % 100% 80% 89.6% 100.0% 88.9% - 100% 100% % % patients started therapy between 02/17-08/17, 2016

18 Safety profile* AE Allergy Anemia ALT/AST increase Creatinine increase Prolnged QT Arrythmias Trombocytopenia Hypoalbuminemia Peripheral neuropathy Skin discoloration * Cohort of 208 patients entered into the endtb EMR

19 Safety profile* Adverse events (AE) 1,281 Number of patients with AE 184 Grade % Grade % Grade 3 3.0% Grade 4 0.7% No data 3.6% Number of AE per patient 6.9 * Cohort of 208 patients entered into the endtb EMR

20 Safety profile, SAE Serious adverse events (SAE) 18 Patients with at least 1 SAE 15 (83.3%) Patients on BDQ-containing regimen 15 SAE related to TB drugs 10 (55.6%) Related to BDQ 5 (50.0%) Prolonged QT 4 Myocardial infarction 1 Hepatitis 1 Relatd to LZD, CFZ and other TB drugs 5 (50.0%) Nephritis 1 Pancytopenia 1 Seizures, tremor 2

21 Safety profile, SAE Serious adverse events (SAE) 18 SAE, not related to TB drugs 8 (44.4%) Stomach cancer 1 Alcohol poisoning 2 Abdominal pain 1 Cardiopulmonary failure 2 Angina pectoris 1 Pneumothorax spontaneous 1 Deaths 5 (27.7%) Death due to TB progression or other conditions 3 Alcohol poisoning (not related) 2

22 Acknowledgement Partners In Health, Boston, MA Partners In Health, Kazakhstan Ministry of Health of Kazakhstan National Scientific Center of Pthisiopulmonology of the MOH of Kazakhstan Regional TB Services of Astana, Almaty cities, Akmolinskaya and Almaty oblasts.