Introducing new and repurposed TB drugs: the endTB experience

Seung, Kwonjune J.; Khan, Uzma; Varaine, Francis; Ahmed, Saman; Bastard, Mathieu; Cloez, S; Damtew, Dagim; Franke, Molly F; Herboczek, Krzysztof; Huerga, Helena; Islam, Shirajul; Karakozian, Hayk; Khachatryan, Naira; Kliesckova, J; Khan, Asif; Khan, Muhammad Umair; Khan, Palwasha; Kotrikadze, Tinatin; Lachenal, Nathalie; Lecca, Leonid; Lenggogeni, Putri; Maretbayeva, S; Melikyan, Nara; Mesic, Anita; Mitnick, Carole D.; Mofolo, Malefetsane; Perrin, Christophe; Richard, Michele; Tassew, Yoseph; Telnov, Alex; Vilbrun, Stalz Charles; Wanjala, S; Rich, Michael; Hewison, Cathy

doi:10.5588/ijtld.20.0141

Cited by 7 publications

(4 citation statements)

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“…Despite a heterogeneous study population from 16 countries, monitoring and reporting were highly uniform. Distinct from prior observational reports [ 9–14 ], the present study deployed a single, externally supported monitoring schedule that included monthly electrocardiograms and audiometry, reported solicited and unsolicited AEs, used standardized a priori definitions of AEs of interest, graded events according to a single severity scale, and received support from a central PV unit [ 4 , 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

Safety of Treatment Regimens Containing Bedaquiline and Delamanid in the endTB Cohort

Hewison

Khan²,

Bastard³

et al. 2022

Clinical Infectious Diseases

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Rationale Safety of treatment for multidrug-resistant tuberculosis (MDR/RR-TB) can be an obstacle to treatment completion Objectives Evaluate safety of longer MDR/RR-TB regimens containing bedaquiline and/or delamanid. Methods Multicentre (16 countries), prospective, observational study, reporting incidence and frequency of clinically relevant adverse events of special interest (AESI) amongst patients who received MDR/RR-TB treatment containing bedaquiline and/or delamanid. The AESIs were defined a priori as important events caused by bedaquiline, delamanid, linezolid, injectables, and other commonly used drugs. Occurrence of these events was also reported by exposure to the likely causative agent. Results Among 2296 patients, the most common clinically relevant AESIs were: peripheral neuropathy in 26.4%, electrolyte depletion in 26.0%, and hearing loss in 13.2% of patients. Per 1000 person-months of treatment, the incidence of these events was 21.5 (95% confidence interval [CI]: 19.8-23.2), 20.7 (95% CI: 19.1-22.4), and 9.7 (95% CI: 8.6-10.8), respectively. QT interval was prolonged in 2.7% or 1.8 (95% CI: 1.4-2.3)/1000 person-months of treatment. Patients who received injectables (N=925) and linezolid (N=1826) were most likely to experience events during exposure: Hearing loss, acute renal failure, or electrolyte depletion occurred in 36.8% or 72.8 (95%CI: 66.0-80.0) times/1000 person-months of injectable drug exposure. Peripheral neuropathy, optic neuritis and/or myelosuppression occurred in 27.8% or 22.8 (95% CI: 20.9-24.8) times/1000 patient-months of linezolid exposure. Conclusions Adverse events often related to linezolid and injectable drugs were more common than those frequently attributed to bedaquiline and delamanid. MDR-TB treatment monitoring schedules and individual drug durations should reflect expected safety profiles of drug combinations.

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Section: Discussionmentioning

confidence: 99%

Safety of Treatment Regimens Containing Bedaquiline and Delamanid in the endTB Cohort

Hewison

Khan²,

Bastard³

et al. 2022

Clinical Infectious Diseases

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“…The possibility of increased rates of cardiotoxicity have limited co-administration of Bdq and Dlm to situations where all other treatment options are exhausted [ 2 ]. Many clinicians and National TB Programs in the areas hardest hit by MDR/RR-TB continue to avoid using Bdq and Dlm in combination out of fear of their potential overlapping toxicity [ 3 ]. Widespread concomitant use is also hampered by limited access to the drugs, especially Dlm, in part related to its high cost, and to the restricted recommendations for its use in international guidelines for MDR/RR-TB treatment [ 4 ].…”

mentioning

confidence: 99%

Safety and Effectiveness Outcomes From a 14-Country Cohort of Patients With Multi-Drug Resistant Tuberculosis Treated Concomitantly With Bedaquiline, Delamanid, and Other Second-Line Drugs

Huerga¹,

Khan²,

Bastard³

et al. 2022

Clinical Infectious Diseases

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Background Concomitant use of bedaquiline (Bdq) and delamanid (Dlm) for multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) has raised concerns about a potentially poor risk-benefit ratio. Yet, this combination is an important alternative for patients infected with strains of TB with complex drug resistance profiles or who cannot tolerate other therapies. We assessed safety and treatment outcomes of MDR/RR-TB patients receiving concomitant Bdq and Dlm, along with other second-line anti-TB drugs. Methods We conducted a multi-centric, prospective observational cohort study across 14 countries among patients receiving concomitant Bdq-Dlm treatment. Patients were recruited between April 2015 and September 2018 and were followed until the end of treatment. All serious adverse events and adverse events of special interest (AESI), leading to a treatment change, or judged significant by a clinician, were systematically monitored and documented. Results Overall, 472 patients received Bdq and Dlm concomitantly. A large majority also received linezolid (89.6%) and clofazimine (84.5%). Nearly all (90.3%) had extensive disease; most (74.2%) had resistance to fluoroquinolones. The most common AESI were peripheral neuropathy (134, 28.4%) and electrolyte depletion (94, 19.9%). Acute kidney injury and myelosuppression were seen in 40 (8.5%) and 24 (5.1%) of patients, respectively. QT prolongation occurred in 7 (1.5%). Overall, 78.0% (358/458) had successful treatment outcomes, 8.9% died and 7.2% experienced treatment failure. Conclusions Concomitant use of Bdq and Dlm, along with linezolid and clofazimine, is safe and effective for MDR/RR-TB patients with extensive disease. Using these drugs concomitantly is a good therapeutic option for patients with resistance to many anti-TB drugs.

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“…Pasien TB MDR menerima jenis obat sebanyak 7 jenis obat TB MDR terdiri atas 4 jenis obat lini kedua ditambah 3 jenis obat lini pertama atau jenis obat baru yang masih sensitif. Kombinasi tersebut untuk memperkuat obat TB MDR melawan kuman M.tuberculosis yang telah resisten (Seung et al, 2020). Pada penelitian ini jenis obat yang diterima pasien kategori <10 jenis obat sebanyak 63 pasien (53,80%).…”

Section: Gambar 4 Grafik Persentase Penggunaan Obat Tb Mdr Berdasarka...unclassified

Profil Penggunaan Obat Tuberculosis Multi Drug Resistant (Mdr) Di Rsud Dr. Moewardi Surakarta, Jawa Tengah

Fitri,

Rani,

Rambe

et al. 2024

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Tuberkulosis Multi Drug Resistant (TB MDR) adalah TB yang disebabkan oleh resistensi kuman tuberkulosis terhadap dua jenis obat anti tuberkulosis (OAT) lini pertama, isoniazid dan rifampisin, baik bersamaan dengan atau tanpa OAT tambahan. Secara global insiden kasus TB MDR pada tahun 2016 berkisar 153.000 pasien dan diantaranya ada 130.000 pasien baru yang memulai pengobatan TB MDR di tahun tersebut, sedangkan keberhasilan terapi TB MDR terhadap pasien yang memulai pengobatan sejak 2014 sebanyak 54%. Total kasus TB MDR pada tahun tersebut juga diketahui pasien meninggal sebanyak 16% dan 8% lainnya gagal dalam pengobatan. Riset ini menggunakan metode deskriptif non-eksperimenal dengan desain penelitian potong lintang yang dilakukan setiap bulan. Data dikumpulkan di Poliklinik TB MDR RSUD dr. Moewardi dari Mei hingga Agustus 2019 melalui penelusuran rekam medis pasien. Hasil penelitian menunjukkan bahwa jenis kelamin laki-laki, sebanyak 67 orang (57,26 persen), orang di bawah 60 tahun, sebanyak 103 orang (88,03 persen), dan orang dengan berat badan tertinggi 33 hingga 50 kg, sebanyak 61 orang (52,10 persen). Jenis obat yang paling banyak dikonsumsi yaitu <10 adalah 63 orang (53,80%), tanpa komorbiditas sebanyak 76 orang (64,96%), riwayat tuberculosis yang kambuh sebanyak 39 orang (33,33%), riwayat sosial yang merokok sebanyak 32 orang (27,35%). Hasil penelitian menunjukkan bahwa yang paling umum adalah pria dan orang di bawah 60 tahun. Pola peresepan obat TB MDR berdasarkan jenis obat yang paling umum digunakan adalah kurang dari 10.

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Introducing new and repurposed TB drugs: the endTB experience

Cited by 7 publications

References 0 publications

Safety of Treatment Regimens Containing Bedaquiline and Delamanid in the endTB Cohort

Safety of Treatment Regimens Containing Bedaquiline and Delamanid in the endTB Cohort

Safety and Effectiveness Outcomes From a 14-Country Cohort of Patients With Multi-Drug Resistant Tuberculosis Treated Concomitantly With Bedaquiline, Delamanid, and Other Second-Line Drugs

Profil Penggunaan Obat Tuberculosis Multi Drug Resistant (Mdr) Di Rsud Dr. Moewardi Surakarta, Jawa Tengah

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