내과 R2 이지훈 N Engl J Med Sep 8

INTRODUCTION EXACERBATIONS OF COPD –Lead to a change in treatment –Accelerated decline in lung function and health status –TREATMENT Inhaled glucocorticoids long-acting β-agonist (LABA) Long-acting muscarinic antagonists (LAMAs) –The benefit of inhaled glucocorticoids in addition to two long- acting bronchodilators has not been fully explored –Withdrawal of Inhaled Steroids during Optimized Bronchodilator Management (WISDOM) trial

METHODS STUDY DESIGN –From February 2009 through July 2013 –multinational, randomized, doubleblind, parallel-group, active- control study –Run-in period (6-week) 18 μg of tiotropium once daily 50 μg of salmeterol xinafoate twice daily 500 μg of fluticasone propionate twice daily –Study period (52-week) stepwise reduction in the fluticasone dose every 6 weeks a total daily dose of 1000 μg to 500 μg, then to 200 μg, and finally to 0 μg (placebo)

METHODS WISDOM Study Design

METHODS PATIENTS –From February 2009 through July 2013 –multinational, randomized, doubleblind, parallel-group, active- control study –Run-in period (6-week) 18 μg of tiotropium once daily 50 μg of salmeterol xinafoate twice daily 500 μg of fluticasone propionate twice daily –Study period (52-week) stepwise reduction in the fluticasone dose every 6 weeks a total daily dose of 1000 μg to 500 μg, then to 200 μg, and finally to 0 μg (placebo)

METHODS END POINTS AND ASSESSMENTS –Primary End Point Time to 1st moderate or severe ontreatment COPD exacerbation during 12-month study period –Secondary End Points The time to the first severe COPD exacerbation The number of moderate or severe COPD exacerbations The change from baseline in lung function (including the trough FEV1, forced vital capacity, and peak expiratory flow rate) Health status - St. George’s Respiratory Questionnaire(SGRQ) Dyspnea - modified Medical Research Council (mMRC) scale

RESULTS

RESULTS

RESULTS PRIMARY ENDPOINT

RESULTS SECONDARY ENDPOINTS –Event rate : 0.95/patient-year vs. 0.91/patient-year

RESULTS SECONDARY ENDPOINTS –FEV1 38ml 43ml

RESULTS SECONDARY ENDPOINTS –HEALTH STATUS mMRC score –At week 18 : vs points (P=0.36) –At week 52 : vs points (P=0.06) SGRQ score –At week 27 : vs (P=0.08) –At week 52 : vs (P=0.047)

RESULTS SAFETY

RESULTS

DISCUSSION No notable differences in COPD exacerbations A small but significant and persistent between-group difference in the FEV1 No significant effect of glucocorticoid withdrawal on the mMRC score, but there was a difference in the total SGRQ score No significant between-group difference in the safety profile