Adverse drug reactions during nontuberculous mycobacterial pulmonary disease treatment: a systematic review and meta-analysis

Abstract

Rationale Nontuberculous mycobacterial pulmonary disease (NTM-PD) treatment involves the long-term administration of multiple drugs, often associated with adverse drug reactions (ADRs). However, the incidence and severity of ADRs during treatment are not fully understood.Objectives We performed a systematic review and meta-analysis of prospective studies reporting ADRs up to June 11, 2025, to assess the burden of ADRs during NTM-PD treatment.Methods We evaluated the incidence rates of ADRs, medication discontinuation, and ADR-related deaths. Secondary outcomes included the clinical manifestations of ADRs and incidence rates according to the causative species.Results In total, 8061 studies were identified through database searches, 36 of which were included in the analysis, including 26 nonrandomized prospective studies (1784 patients) and 10 randomized controlled studies (1511 patients). The overall ADR incidence rate was 59% (95% CI, 39%-78%), with ADR-related drug discontinuation and death rates of 15% (95% CI, 10%-20%) and 2% (95% CI, 1%-3%), respectively. The clinical manifestation rates of ADRs ranged from 2% to 65%, with gastrointestinal symptoms being the most common. For the treatment of NTM-PD caused by Mycobacterium avium complex, the ADR incidence rate was 57% (95% CI, 31%-79%), whereas that for Mycobacterium abscessus was 39% (95% CI 15%-70%). The outcomes were similar between randomized and nonrandomized studies.Conclusions ADRs during NTM-PD treatment are notably frequent, leading to drug discontinuation and possible mortality. Clinicians should be vigilant of ADRs during NTM-PD management, and further research is required to alleviate their burden and improve outcomes.