Adverse Drug Reactions During Nontuberculous Mycobacterial Pulmonary Disease Treatment: A Systematic Review and Meta-analysis

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. Objective: 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, 8,061 studies were identified through database searches, 36 of which were included in the analysis, including 26 non-randomized prospective studies (1,784 patients) and 10 randomized controlled studies (1,511 patients). The overall ADR incidence rate was 59% (95% confidence interval 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 non-randomized 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.