Several recent trials in chronic obstructive pulmonary disease (COPD) have assessed the effectiveness of the fluticasone–salmeterol combination inhaler in preventing COPD exacerbations, while finding an increased risk of pneumonia. The number needed to treat (NNT) is a simple measure to perform the comparative benefit–risk impact, but its calculation involving repeated outcome events such as COPD exacerbations has been incorrect. We describe the proper methods to calculate the NNT and, using data from published trials, apply them to evaluate the relative impact of fluticasone–salmeterol treatment on exacerbations and pneumonias in patients with COPD.

We review the fundamental definition of NNT and quantify it for situations with varying follow-up times. We review the ‘event-based’ NNT, proposed and used for repeated event outcomes, show its inaccuracy, describe its proper use and provide an approximate formula for its application.

We show that a 1-year trial of the fluticasone–salmeterol combination versus salmeterol used the incorrect event-based approach to calculate the NNT as two patients that need to be treated for 1 year to prevent one COPD exacerbation, when the proper calculation results in a NNT of 14. In contrast, 20 patients need to be treated to induce one pneumonia case. For the TORCH trial, the NNT is 44 patients treated for 3 years with fluticasone–salmeterol versus salmeterol to prevent one exacerbation compared with 16 patients to induce one pneumonia case.

The NNT is a useful measure of the effect of drugs, but its proper calculation is essential to prevent misleading clinical practice guidelines.

Clinical trials in cystic fibrosis (CF) have been hindered by the paucity of well characterised and clinically relevant outcome measures.

To evaluate a range of conventional and novel biomarkers of CF lung disease in a multicentre setting as a contributing study in selecting outcome assays for a clinical trial of CFTR gene therapy.

A multicentre observational study of adult and paediatric patients with CF (>10 years) treated for a physician-defined exacerbation of CF pulmonary symptoms. Measurements were performed at commencement and immediately after a course of intravenous antibiotics. Disease activity was assessed using 46 assays across five key domains: symptoms, lung physiology, structural changes on CT, pulmonary and systemic inflammatory markers.

Statistically significant improvements were seen in forced expiratory volume in 1 s (p<0.001, n=32), lung clearance index (p<0.01, n=32), symptoms (p<0.0001, n=37), CT scores for airway wall thickness (p<0.01, n=31), air trapping (p<0.01, n=30) and large mucus plugs (p=0.0001, n=31), serum C-reactive protein (p<0.0001, n=34), serum interleukin-6 (p<0.0001, n=33) and serum calprotectin (p<0.0001, n=31).

We identify the key biomarkers of inflammation, imaging and physiology that alter alongside symptomatic improvement following treatment of an acute CF exacerbation. These data, in parallel with our study of biomarkers in patients with stable CF, provide important guidance in choosing optimal biomarkers for novel therapies. Further, they highlight that such acute therapy predominantly improves large airway parameters and systemic inflammation, but has less effect on airway inflammation.

The inhaled corticosteroid fluticasone furoate (FF) in combination with the long-acting β₂ agonist vilanterol (VI) is in development for asthma and chronic obstructive pulmonary disease.

To assess the safety and tolerability of FF/VI over 52 weeks in patients with asthma.

Patients (aged ≥12 years; on inhaled corticosteroid) were randomised (2:2:1) to FF/VI 100/25 µg or FF/VI 200/25 µg once daily in the evening, or fluticasone propionate (FP) 500 µg twice daily. Safety evaluations included adverse events (AEs), non-fasting glucose, potassium, 24-h urinary cortisol excretion, ophthalmic assessments, heart rate and pulse rate.

On-treatment AEs were similar across groups (FF/VI 66–69%; 73% FP). Oral candidiasis/oropharyngeal candidiasis was more common with FF/VI (6–7%) than FP (3%). Twelve serious AEs were reported; one (worsening hepatitis B on FP) was considered drug related. Statistically significant cortisol suppression was seen with FP compared with both FF/VI groups at Weeks 12 and 28 (ratios [95% CI] to FP ranged from 1.43 [1.11 to 1.84] to 1.67 [1.34 to 2.08]; p≤0.006), but not at Week 52 (ratios to FP were 1.05 [0.83 to 1.33] for FF/VI 100/25 µg and 1.09 [0.87 to 1.38] for FF/VI 200/25 µg). No clinically important changes in non-fasting glucose, potassium, QT interval corrected using Fridericia's formula (QTc[F]) or ophthalmic assessments were reported. Pulse rate (10 min post dose [T_max], Week 52) was significantly increased with FF/VI versus FP (3.4 bpm, 95% CI 1.3 to 5.6; p=0.002 [FF/VI 100/25 µg]; 3.4 bpm, 95% CI 1.2 to 5.6; p=0.003 [FF/VI 200/25 µg]). Mean heart rate (24-h Holter monitoring) decreased from screening values in all groups (0.2–1.1 bpm FF/VI vs 5 bpm FP; Week 52).

FF/VI (100/25 µg or 200/25 µg) administered once daily over 52 weeks was well tolerated by patients aged ≥12 years with asthma. The overall safety profile of FF/VI did not reveal any findings of significant clinical concern.

NCT01018186