Compassionate use of bedaquiline in a cohort of Indian drug resistant tuberculosis(DR-TB) patients

Abstract

Background: Bedaquiline (BDQ), a mycobaterial ATP synthase inhibitor, is a new bactericidal anti TB drug. It was available for compassionate use (CU) in DR-TB patients in India from 2012. Aim: We present the outcomes of 20 DR-TB patients who received BDQ for CU. This is the largest such series from India. Methods: BDQ was applied for in 27 patients with DR-TB who had failed treatment on standard second line drugs(SLD). We received approval from Janssen pharmaceuticals for 20 patients. These were followed up to evaluate clinical, microbiological and radiographic outcomes. QTcF intervals were serially monitored. Results: The mean time for procurement of BDQ was 50 days. 20 patients completed 24 weeks of BDQ. Of these, 7 had MDR-TB with quinolone resistance while 13 had XDR-TB. Mean number of drugs in the background regimen(BR) was 5.6. Clinical improvement was seen in all 20 patients with a mean weight gain of 4.6 kg. Radiographic status improved in 17 patients; it was static in 3 patients. 15 patients converted sputum while 5 patients failed to convert. Responders had more drugs in the BR compared to non-responders(6 vs 4.7). Duration of prior SLD use was shorter in responders(10.58 months) as compared to non responders(42.28 months). Though QTcF increased by a mean of 49 ms, BDQ interruption was not required. There was no mortality. Conclusion: BDQ is a promising new drug for DR-TB. 75% of patients in our cohort who failed earlier on SLD showed sputum conversion. Though well tolerated, QTcF needs monitoring. Success with BDQ may be better achieved if it is introduced earlier in the course of the disease with an adequate BR. Expanded access in the National TB program is urgently needed.