The Introduction of Bedaquiline Regimen for Drug-Resistant Tuberculosis in the Philippines: An Operational Study

Objectives: Bedaquiline (BDQ) is the first new anti-tuberculosis (TB) drug introduced to the market after 45 years. Recent studies have shown the potential benefits of adding bedaquiline to regimens for drug-resistant TB (DR-TB). In search of more effective regimens for DR-TB, bedaquiline was introduced in the TB program in the Philippines under operational research to assess its effectiveness, safety, and tolerability when given with background regimens among patients with multi-or extensively DR-TB (MDR/XDR-TB). Design: A prospective cohort study of patients with MDR/XDR-TB was given with a bedaquiline-containing regimen from June 2016 to May 2017. Demographic data, presence of comorbidities, and microbiologic profile on entry were recorded. Bedaquiline was administered at the recommended dose of 400 mg once daily for 14 days, then 200 mg three times a week for 22 weeks together with World Health Organization (WHO)-compliant background regimen. The time to culture conversion, interim outcomes at the 6th month of treatment, end-of-treatment outcomes, and post-treatment follow-up outcomes after one year was determined. The frequency and severity of adverse events (SAE) were recorded as part of pharmacovigilance. Results: Seventy-five patients were given with bedaquiline-containing regimen during the study period. Forty-two (56.0%) had second-line injectable resistance, 23 (30.7%) had fluoroquinolone-resistance, 6 (8.0%) had MDR-TB, and 4 (5.3%) had XDR-TB. In the 6th month of post-enrolment, 79% were culture-negative. The treatment success rate was 65.3% (37 were cured and 12 completed treatment), 7 (9.3%) died, 17 (22.7%) lost to follow-up, and 2 (2.7%) were withdrawn from treatment. Adverse events included vomiting (80%), dizziness (69%), nausea (52%), cough (44%), and headache (36%). The post-treatment follow-up of 49 patients in the 12th month showed 92% were culture-negative while 8% of TBC were not done. Conclusion: Bedaquiline-containing regimens for patients with MDR/XDR-TB were highly effective with an acceptable safety profile and favorable treatment outcomes, but the proportion of patients who lost to follow-up remains substantial.

Interim Outcomes and Adverse Events among Drug-Resistant Tuberculosis Patients Treated with Bedaquiline in the Philippines

Objectives: This study aimed to assess the interim outcomes for drug-resistant tuberculosis (DR-TB) patients treated with bedaquiline regimen under the operational research conditions compared to DR-TB patients treated without bedaquiline in their regimen, and to describe the adverse events that occurred among patients treated with bedaquiline in the Philippines. Design: Patients who were treated with a bedaquiline-containing regimen from June 2016 to May 2017 were included in this study as the intervention group, while patients who were treated without bedaquiline regimen from January 2013 to May 2016 were included as the comparison group. The interim treatment outcomes were compared using Chi-square test. The analysis of time to culture conversion within 6 months of treatment was conducted. A Cox proportional hazard model was constructed to identify the variables associated with a favorable interim treatment outcome. The R program was used for statistical analysis. Results: On the 6th month of treatment, the culture conversion for patients treated with a bedaquiline-containing regimen was significantly higher than with the comparison group [63/75 (84.0%) vs 84/117 (71.8%), p = 0.012)]. Nearly 15% of the patients treated with bedaquiline were lost to follow-up. Frequent adverse events included vomiting, dizziness, nausea, joint pain, and abdominal pain. Conclusion: The patients who were treated with bedaquiline-containing regimen have better interim treatment outcomes than those treated without bedaquiline, but the proportion of patients who were lost to follow-up remains substantial.

Effectiveness and Safety of 9-Month Treatment Regimen for Multidrug-Resistant Tuberculosis in the Philippines

Background: The Philippines has a burden of drug-resistant tuberculosis (DR-TB). One of the key challenges in the programmatic management of DR-TB (PMDT) is the high rate of loss to follow-up (38% in the 2010 cohort). An urgent need for a shorter, more tolerable, less expensive treatment regimen exists. The aim of the operational study is to determine the efficacy and safety of the short treatment regimen among drug resistant TB. Methods: This is a prospective single-arm cohort study evaluating the effectiveness and safety of a shorter 9 - 11-month treatment regimen (9MTR) for rifampicin-resistant/multi-drug resistant TB (RR/MDR-TB) in 10 PMDT facilities. All eligible consenting adult patients with rifampicin-resistant TB were enrolled and received the standardized 9-month treatment regimen (9MTR), including injectables, with a follow-up after 12 months of treatment completion. Results: A total of 329 patients were enrolled from July 2015 to December 2016. At the 6th month post-enrollment, 256 (77.8%) of them had culture-negative test results. The end-of-treatment success rate was 74.1% (224 [68.0%] were cured and 20 [6.1%] completed the treatment). On the other hand, 10 (3.0%) died, 41 (12.5%) lost to follow-up, 33 (10.0%) withdrawn, 1 (0.3%) treatment failure. In the 12th month after 9MTR completion, among the 244 patients with successful treatment, 198 (81.1%) had culture-negative results, while there were 46 patients whose culture tests were not done. One patient developed TB relapse with fluoroquinolone resistance. The majority of the adverse events were mild that occurred mostly during the first 6 months of treatment. Conclusion: The 9-month treatment regimen had a high treatment success rate with a favorable safety profile. The loss to follow-up was reduced;however, it was still a challenge. The introduction of the 9MTR via operational research had a major impact on building national capacity and infrastructure for the programmatic adoption of a new regimen. Ten PMDT centers received training and experience, created diagnostic pathways, and active drug safety monitoring and management were built.