Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report

Abstract

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

Aim of this prospective study was to evaluate the frequency and severity of AEs 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.

AEs 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% males, 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 AE episodes were reported: 447 (447/504, 88.7%) were classified as minor (grade 1–2) and 57 (57/504, 11.3%) as serious (grade 3–5).

The majority of the 57 serious AEs reported by 55 patients (51/57; 89.5%) ultimately resolved. Among patients reporting serious AEs some drugs held responsible were discontinued: bedaquiline in 0.35% (2/577), delamanid in 0.8% (1/121), linezolid in 1.9% (10/536) and clofazimine in 1.4% (3/213) of patients.

Serious AEs were reported in 6.9% (9/131) of patients treated with amikacin, 0.4% (1/221) with ethionamide/prothionamide, 2.8% (15/536) with linezolid and 1.8% (8/498) with cycloserine/terizidone.

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