Adrenal function recovery after durable oral corticosteroid sparing with benralizumab in the PONENTE study

Background Oral corticosteroid (OCS) dependence among patients with severe eosinophilic asthma can cause adverse outcomes, including adrenal insufficiency. PONENTE's OCS reduction phase showed that, following benralizumab initiation, 91.5% of patients eliminated corticosteroids or achieved a final dosage ≤5 mg·day-1 (median (range) 0.0 (0.0-40.0) mg). Methods The maintenance phase assessed the durability of corticosteroid reduction and further adrenal function recovery. For ~6 months, patients continued benralizumab 30 mg every 8 weeks without corticosteroids or with the final dosage achieved during the reduction phase. Investigators could prescribe corticosteroids for asthma exacerbations or increase daily dosages for asthma control deteriorations. Outcomes included changes in daily OCS dosage, Asthma Control Questionnaire (ACQ)-6 and St George's Respiratory Questionnaire (SGRQ), as well as adrenal status, asthma exacerbations and adverse events. Results 598 patients entered PONENTE; 563 (94.1%) completed the reduction phase and entered the maintenance phase. From the end of reduction to the end of maintenance, the median (range) OCS dosage was unchanged (0.0 (0.0-40.0) mg), 3.2% (n=18/563) of patients experienced daily dosage increases, the mean ACQ-6 score decreased from 1.26 to 1.18 and 84.5% (n=476/563) of patients were exacerbation free. The mean SGRQ improvement (-19.65 points) from baseline to the end of maintenance indicated substantial quality-of-life improvements. Of patients entering the maintenance phase with adrenal insufficiency, 32.4% (n=104/321) demonstrated an improvement in adrenal function. Adverse events were consistent with previous reports. Conclusions Most patients successfully maintained maximal OCS reduction while achieving improved asthma control with few exacerbations and maintaining or recovering adrenal function

Fluticasone propionate/formoterol for COPD management: A randomized controlled trial

Purpose: To evaluate fluticasone propionate/formoterol (FP/FORM) in COPD. Patients and methods: COPD patients with forced expiratory volume in 1 s (FEV1) â\u89¤50% predicted and â\u89¥1 moderate/severe COPD exacerbation in the last 12 months were randomized to FP/FORM 500/20 or 250/10 μg bid, or formoterol (FORM) 12 μg bid for 52 weeks. The primary outcome was the annualized rate of moderate/severe COPD exacerbations. Results: In total, 1,765 patients were randomized. There were fewer discontinuations with FP/FORM 500/20 μg (20.6%) and 250/10 μg (24.0%) compared with FORM (26.1%). None of the two FP/FORM doses reduced the moderate/severe exacerbation rate versus FORM (rate ratios [RR]: 0.93; Pâ\u89¤0.402). There was a trend toward a lower moderate/severe exacerbation rate with FP/FORM 500/20 μg versus FORM in patients with â\u89¥2 exacerbations in the preceding year (RR: 0.79; P=0.084). Pre-and post-dose FEV1 and forced vital capacity were greater with FP/FORM 500/20 μg versus FORM (Pâ\u89¤0.039). There was a trend toward a lower EXAcerbations of Chronic pulmonary disease Tool (EXACT) exacerbation rate with FP/FORM 500/20 μg versus FORM (RR: 0.87; P=0.077). There were more St Georgeâ\u80\u99s Respiratory Questionnaire for COPD (SGRQ-C) responders with FP/FORM 500/20 μg than FORM (odds ratios [OR] at weeks 6, 23 and 52 â\u89¥1.28; Pâ\u89¤0.054). EXACT-respiratory symptoms total and breathlessness scores were lower with both FP/FORM 500/20 μg and 250/10 μg versus FORM (Pâ\u89¤0.066). Acute β2-agonist-induced effects and 24-hour Holter findings were similar for all treatments. Mean 24-hour urinary cortisol was similarly reduced with both FP/FORM doses. Radiologically confirmed pneumonia was seen in 2.4%, 3.2% and 1.5% of FP/FORM 500/20 μg, FP/FORM 250/10 μg and FORM-treated patients, respectively. Adverse events were otherwise similar across treatment groups. Conclusion: FP/FORM did not reduce exacerbation rates versus FORM. Numerical benefits were observed with FP/FORM 500/20 μg versus FORM for secondary variables, including lung function, EXACT exacerbations, SGRQ-C and EXACT-respiratory symptoms total and breathlessness scores. Few efficacy differences were evident between FP/FORM 250/10 μg and FORM. Pneumonia was more frequent in FP/FORM-treated patients, although the absolute difference was low. Adverse events were otherwise similar between treatments