Background: In Japan, Mycobacterium avium complex lung disease (MAC-LD) is the most common in nontuberculous mycobacterial lung disease. Patients often experience adverse events, resulting in the discontinuation of treatment, which causes treatment failure. The Japanese Adverse Drug Event Report (JADER) database is a database of adverse events and reflects the clinical practice in Japan. We can collect large-scale data cost-effectively and detect signals of potential adverse events such as reporting odds ratio (ROR) by using spontaneous reporting systems.
Methods: We included cases of MAC-LD between April 2004 and June 2017. We investigated sex, age, and medications that may have caused the adverse events, outcomes, and time of onset. We calculated the safety signal index as the ROR. Time-to-event analysis was performed using the Weibull distribution.
Results: The total number of adverse effects of CAM, EB, and RFP was 2780, with 806 patients. In the overall adverse events, hematologic and lymphatic disorders were the most common adverse events, with 11%, followed by eye disorders (10.6%), and hepatobiliary disorders (8.9%). The outcomes were as follows: recovery, 40.1%; remission, 27.1%; non-recovery, 11.2%; and death, 7.2%. Regarding the most common onset time of CAM, EB, and RFP was within 120 days at 40%, 181–300 days at 43.6%, and within 120 days at 88.5%. For CAM, the RORs of infections and infestations, hepatobiliary system disorders, and immune system disorders were 4.13 (95% CI, 2.3–7.44), 2.61 (95% CI, 1.39–4.91), and 2.38 (95% CI, 1.04–5.44). For EB, the ROR of eye disorders was 215.79 (95% CI, 132.62–351.12). For RFP, the RORs of renal and urinary tract disorders and investigations were 7.03 (95% CI, 3.35–14.77) and 6.99 (95% CI, 3.22–15.18). The β value of EB was 2.07 (95% CI, 1.48–2.76), which was classified as wear-out failure type.
Conclusions: For MAC-LD, adverse events of EB occur after 180 days, whereas the adverse events of CAM and RFP occur early in the course of treatment.