Longitudinal Changes in St. George's Respiratory Questionnaire Scores Following Culture Conversion in Patients With Mycobacterium Avium Complex Lung Disease

Abstract Rationale Amikacin liposome inhalation suspension (ALIS) is indicated for treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen for adult patients who do not achieve negative sputum cultures after at least 6 consecutive months of multidrug antibiotic therapy. In the Phase 3 CONVERT trial (NCT02344004), patients were randomized to receive ALIS+guideline-based therapy (GBT) or GBT alone. Patients with culture conversion by Month 6 continued treatment for 12 months after conversion and were followed for 12 months off treatment. Evidence regarding changes in patient-reported outcomes after culture conversion is lacking. This analysis aimed to evaluate longitudinal changes in St. George's Respiratory Questionnaire (SGRQ) scores in patients who achieved culture conversion by Month 6. Methods The SGRQ is a self-administered instrument assessing overall health, daily life, and perceived well-being via 50 items including 76 weighted responses in a set of 17 questions; score reductions indicate improvement. The questionnaire was administered at baseline, Months 3, 6, 8, 12, end-of-treatment (EOT), and 3-month follow-up visits. Changes in SGRQ scores from baseline and the proportion of patients exceeding the minimal clinically important difference (MCID) threshold based on published literature were calculated for all visits. A reduction in the total SGRQ score of 4 units is recognized as a clinically meaningful improvement in other disease states; this threshold was applied as the MCID in this analysis. Changes from baseline scores and the percentages of patients achieving MCID were summarized descriptively. Linear mixed models for repeated measures (MMRMs) were fitted to change-from-baseline scores. Results There were 75 patients (n=65, ALIS+GBT; n=10 GBT alone) who achieved culture conversion by Month 6. Among these patients, mean total SGRQ score did not change meaningfully during the treatment period; however, it declined significantly (-7.1 points, P<0.05) at EOT+3 months compared with baseline. At EOT+3 months, 58% of patients who achieved culture conversion by Month 6 had an improvement in total SGRQ score that met or exceeded the MCID. The same trend was observed across the 3 health domains measured by the SGRQ, with a 7.8 point reduction in Symptoms, 6.2 point reduction in Activity, and 7.9 point reduction in Impact at EOT+3 months (P<0.05 for all). Conclusions After treatment was completed, patients who achieved sputum culture conversion experienced significant reduction in SGRQ scores from baseline, which may indicate improvement across all included health domains.