Amikacin confers no new safety concerns in Mycobacterium avium complex lung disease
No new safety signals were found with the use of amikacin liposome inhalation suspension added to guideline-based therapy for patients with refractory Mycobacterium avium complex lung disease, according to researchers.
“Amikacin liposome inhalation suspension was developed to deliver high concentrations of amikacin to the site of infection while limiting systemic exposure,” Kevin L. Winthrop, MD, MPH, from the division of infectious diseases at Oregon Health and Science University School of Medicine and Public Health, and colleagues wrote in the Annals of the American Thoracic Society. “International guidelines for the treatment of Mycobacterium avium lung disease recommend the addition of amikacin liposome inhalation suspension to guideline-based therapy in patients who fail to convert after 6 months of treatment.”
The open-label extension of the CONVERT study included 163 adults with refractory Mycobacterium avium complex lung disease (mean age, 64.8 years; 64.4% women) who did not achieve culture conversion by 6 months from February 2016 to October 2018. Patients were assigned to receive once-daily amikacin liposome inhalation suspension (ALIS) at 590 mg plus guideline-based therapy for 12 months.
Patients in the ALIS-naive cohort (n = 90) were those randomly assigned to guideline-based therapy only in the CONVERT study, and those in the prior-ALIS cohort (n = 73) were those randomly assigned to ALIS plus guideline-based therapy in the CONVERT study.
The primary outcome was the safety and tolerability of ALIS at 12 months. Secondary outcomes included culture conversion by 6 and 12 months.
All patients received at least one ALIS dose with a median duration of treatment of 11.6 months in both cohorts.
Respiratory treatment-emergent adverse events were reported by 83.3% of patients in the ALIS-naive cohort and 46.6% of patients in the prior-ALIS cohort. In addition, serious treatment-emergent adverse events were reported among 35.6% of patients in the ALIS-naive cohort and 27.4% of patients in the prior-ALIS cohort.
Researchers observed infrequent nephrotoxicity-related treatment-emergent adverse events and measured hearing decline among both the ALIS-naive and prior-ALIS cohorts.
Among those in the ALIS-naive cohort, 26.7% of patients achieved culture conversion at 6 months and 33.3% achieved culture conversion at 12 months compared with 9.6% and 13.7%, respectively, of patients in the prior-ALIS cohort.
According to Winthrop, these results were not surprising, as researchers were hoping to see no significant ototoxicity or renal toxicity. However, given that amikacin is inhaled and there is little systemic exposure, Winthrop said, he and colleagues were fortunate to see only a small percentage of patients reporting tinnitus and no other aminoglycoside toxicities.
“Similar safety and efficacy trends were observed between the ALIS-naive cohort and the ALIS guideline-based therapy arm of the CONVERT study, and the results in the prior-ALIS cohort suggest the potential for ALIS use of greater than 1 year,” the researchers wrote.
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Kevin L. Winthrop, MD, MPH, can be reached at winthrop@ohsu.edu.