Efficacy of alvelestat on SGRQ in patients with alpha-1 antitrypsin deficiency and mild airflow limitation: A pooled analysis from two Phase 2 studies

<bold>Introduction:</bold> AATD patients with GOLD Grade 1 airflow limitation (FEV1≥80%) have not been regularly included in AATD studies. In the 12-week ATALANTa study in a younger subpopulation with mild airflow limitation, alvelestat showed SGRQ improvements in the Total and Activity scores (−2.8 change from baseline, p=0.2 and -7.4, p=0.007 respectively). <bold>Aims:</bold> To determine the effect of 12 weeks alvelestat treatment (120mg BID or 240mg BID) on SGRQ Total/Activity scores in a pooled analysis of patients with GOLD 1 airflow limitation in the ASTRAEUS and ATALANTa Phase 2 studies. <bold>Methods:</bold> Patients with GOLD 1 airflow limitation at baseline were pooled. Within-group and between-group effects on SGRQ were analysed using a mixed model repeated measures approach. <bold>Results:</bold> The pool included 39 patients (22 on alvelestat, 17 on placebo); 17 from ASTRAEUS and 22 from ATALANTa. Mean (SD) baseline age was 49.1 years (11.3), FEV1 was 95.5% (10.9). After 12 weeks of alvelestat, mean change from baseline of SGRQ Total was -2.6 (p=0.1) and SGRQ Activity was -6.5 (p=0.005). Changes for placebo were not statistically significant. Between group changes for both scores were numerically superior with alvelestat vs. placebo but not significant. <bold>Conclusions:</bold> In a pooled analysis, alvelestat for 12 weeks was associated with improvement in SGRQ scores in patients with AATD and GOLD 1 airflow limitation. <fig><object-id>erj;64/suppl_68/PA3005/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>