Natural history and burden of refractory Mycobacterium avium complex pulmonary disease: Insights from the US Bronchiectasis and Nontuberculous Mycobacterial Research Registry

BACKGROUND: Managing Mycobacterium avium complex pulmonary disease (MACPD) is challenging for refractory disease. This study used real-world data to describe natural history and burden of refractory MACPD. METHODS: US Bronchiectasis and Nontuberculous Mycobacteria Research Registry data were analyzed retrospectively. Patients treated for MACPD were categorized as refractory (defined as receiving oral clofazimine, bedaquiline, inhaled amikacin, or amikacin liposome inhalation suspension, or remaining culture positive ≥6 months during treatment) or nonrefractory. Patient characteristics and healthcare resource utilization were compared. Longitudinal assessment over adjacent visits (pre-refractory and refractory) focused on hospitalizations and exacerbations among incident refractory cases. RESULTS: Of 1064 patients treated for MACPD, 43.4 % were refractory and 56.6 % nonrefractory. At MACPD treatment initiation, refractory patients had lower mean BMI (21.3 vs 22.2; p < 0.001) and FVC% predicted (78.4 vs 84.8; p < 0.001), more prevalent fibrocavitary/cavitary disease (33.5 % vs 16.3 %; p < 0.001) and bronchiectasis (96.2 % vs 89.7 %; p < 0.001). Exacerbations (54.1 % and 50.5 %), hospitalizations (18.8 % and 17.3 %), chronic cough (78.0 % and 77.7 %), and baseline lung severity were common in both groups. The natural history of the disease among 197 incident refractory cases showed that exacerbations (45.6 % and 39.4 %) and hospitalizations (13.3 % and 12.8 %) were common at pre-refractory and refractory visits. CONCLUSIONS: MACPD imposes substantial burden on patients in terms of symptoms, exacerbations, and hospitalizations. Disease burden was present among refractory patients, at pre-refractory and refractory visits ≥1 year later, and non-refractory patients. Understanding patient characteristics at time of treatment may help timely identification and management of refractory MACPD.