Reduction in exacerbations with itepekimab in former smokers with chronic obstructive pulmonary disease (COPD) by prior exacerbation frequency

<bold>Rationale:</bold> Itepekimab significantly reduced exacerbations of COPD (ECOPD) in former smokers but not in the overall study population of a phase 2 study. <bold>Aim:</bold> To investigate itepekimab efficacy in former smokers with moderate-to-severe COPD by exacerbation history. <bold>Methods:</bold> The phase 2a study (<ext-link>NCT03546907</ext-link>) population consisted of 343 current/former smokers with moderate-to-severe COPD who had ≥2 moderate or ≥1 severe ECOPD in the past year on a stable double/triple inhaled regimen and were randomized 1:1 to itepekimab 300 mg q2w or placebo for 24–52 weeks. Here we analyzed the former smokers by 2 or ≥3 moderate-severe ECOPD in the previous year before baseline. <bold>Results:</bold> In 343 former smokers, itepekimab increased time to first moderate-to-severe ECOPD event (Figure) and resulted in fewer moderate-to-severe ECOPD events compared to placebo, independently of baseline exacerbations (2: RR 0.49; 95% CI 0.29–0.85; nominal P 0.011; ≥3: RR 0.49; 95% CI 0.26–0.93; P=0.029). <bold>Conclusions:</bold> Itepekimab significantly increased time to ECOPD and reduced the frequency of ECOPD in former smokers, irrespective of exacerbation history. These findings will be confirmed by further studies. <bold>Figure</bold>. Prior year’s, Kaplan–Meier plots of time to first moderate-to-severe ECOPD event among former smokers by baseline ECOPD frequency. <fig><object-id>erj;64/suppl_68/OA3645/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>