Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report
Authors: Borisov Sergey , Danila Edvardas , Maryandyshev Andrei , Dalcolmo Margareth , Miliauskas Skaidrius , Kuksa Liga , Manga Selene , Skrahina Alena , Diktanas Saulius , Codecasa Luigi Ruffo , Aleksa Alena , Bruchfeld Judith , Koleva Antoniya , Piubello Alberto , Udwadia Zarir Farokh , Akkerman Onno W. , Belilovski Evgeny , Bernal Enrique , Boeree Martin J. , Cadiñanos Loidi Julen , Cai Qingshan , Cebrian Gallardo Jose Joaquín , Dara Masoud , Davidavičienė Edita , Forsman Lina Davies , De Los Rios Jorge , Denholm Justin , Drakšienė Jacinta , Duarte Raquel , Elamin Seifeldin Eltaeb , Escobar Salinas Nadia , Ferrarese Maurizio , Filippov Alexey , Garcia Ana , García-García José-María , Gaudiesiute Ieva , Gavazova Blagovesta , Gayoso Regina , Gomez Rosso Roscio , Gruslys Vygantas , Gualano Gina , Hoefsloot Wouter , Jonsson Jerker , Khimova Elena , Kunst Heinke , Laniado-Laborín Rafael , Li Yang , Magis-Escurra Cecile , Manfrin Vinicio , Marchese Valentina , Martínez Robles Elena , Matteelli Alberto , Mazza-Stalder Jesica , Moschos Charalampos , Muñoz-Torrico Marcela , Mustafa Hamdan Hamdan , Nakčerienė Birutė , Nicod Laurent , Nieto Marcos Magnolia , Palmero Domingo Juan , Palmieri Fabrizio , Papavasileiou Apostolos , Payen Marie-Christine , Pontarelli Agostina , Quirós Sarai , Rendon Adrian , Saderi Laura , Šmite Agnese , Solovic Ivan , Souleymane Mahamadou Bassirou , Tadolini Marina , van den Boom Martin , Vescovo Marisa , Viggiani Pietro , Yedilbayev Askar , Zablockis Rolandas , Zhurkin Dmitry , Zignol Matteo , Visca Dina , Spanevello Antonio , Caminero José A. , Alffenaar Jan-Willem , Tiberi Simon , Centis Rosella , D'Ambrosio Lia , Pontali Emanuele , Sotgiu Giovanni , Migliori Giovanni Battista 
Published: October 2019

The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.

The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e.bedaquiline, delamanid) and repurposed (i.e.clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.

Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1–2) and 57 (11.3%) as serious (grade 3–5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.

The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.