A response to: Letter to the editor regarding "Fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy compared with other therapies for the treatment of COPD: A network meta-analysis".

This is the final version. Available from Springer via the DOI in this record. Data Availability: The datasets analyzed during the current study are available from the corresponding author on reasonable request

Comparative efficacy of Umeclidinium/Vilanterol versus other bronchodilators for the treatment of chronic obstructive pulmonary disease: A network meta-analysis.

This is the final version. Available from Springer via the DOI in this record. Data Availability: Anonymised individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com. Extracted data summaries are available upon request to the authors.INTRODUCTION: Few randomised controlled trials (RCTs) have directly compared long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) dual maintenance therapies for patients with chronic obstructive pulmonary disease (COPD). This systematic literature review and network meta-analysis (NMA) compared the efficacy of umeclidinium/vilanterol (UMEC/VI) versus other dual and mono-bronchodilator therapies in symptomatic patients with COPD. METHODS: A systematic literature review (October 2015-November 2020) was performed to identify RCTs ≥ 8 weeks long in adult patients with COPD that compared LAMA/LABA combinations against any long-acting bronchodilator-containing dual therapy or monotherapy. Data extracted on changes from baseline in trough forced expiratory volume in 1 s (FEV1), St George's Respiratory Questionnaire (SGRQ) total score, Transitional Dyspnoea Index (TDI) focal score, rescue medication use and moderate/severe exacerbation rate were analysed using an NMA in a frequentist framework. The primary comparison was at 24 weeks. Fixed effects model results are presented. RESULTS: The NMA included 69 full-length publications (including 10 GSK clinical study reports) reporting 49 studies. At 24 weeks, UMEC/VI provided statistically significant greater improvements in FEV1 versus all dual therapy and monotherapy comparators. UMEC/VI provided similar improvements in SGRQ total score compared with all other LAMA/LABAs, and significantly greater improvements versus UMEC 125 μg, glycopyrronium 50 μg, glycopyrronium 18 μg, tiotropium 18 μg and salmeterol 50 μg. UMEC/VI also provided significantly better outcomes versus some comparators for TDI focal score, rescue medication use, annualised moderate/severe exacerbation rate, and time to first moderate/severe exacerbation. CONCLUSION: UMEC/VI provided generally better outcomes compared with LAMA or LABA monotherapies, and consistent improvements in lung function (measured by change from baseline in trough FEV1 at 24 weeks) versus dual therapies. Treatment with UMEC/VI may improve outcomes for symptomatic patients with COPD compared with alternative maintenance treatments.GlaxoSmithKlei

Fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy compared with other therapies for the treatment of COPD: A network meta-analysis.

This is the final version. Available from Springer via the DOI in this record. Data Availability: The datasets analyzed during the current study are available from the corresponding author on reasonable request.INTRODUCTION: Randomized controlled trials (RCTs) comparing triple therapies (inhaled corticosteroid [ICS], long-acting β2-agonist [LABA], and long-acting muscarinic antagonist [LAMA]) for the treatment of chronic obstructive pulmonary disease (COPD) are limited. This network meta-analysis (NMA) investigated the comparative efficacy of single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus any triple (ICS/LABA/LAMA) combinations and dual therapies in patients with COPD. METHODS: This NMA was conducted on the basis of a systematic literature review (SLR), which identified RCTs in adults aged at least 40 years with COPD. The RCTs compared different ICS/LABA/LAMA combinations or an ICS/LABA/LAMA combination with any dual therapy (ICS/LABA or LAMA/LABA). Outcomes of interest included forced expiratory volume in 1 s (FEV1), annualized rate of combined moderate and severe exacerbations, St George's Respiratory Questionnaire (SGRQ) total score and SGRQ responders, transition dyspnea index focal score, and rescue medication use (RMU). Analyses were conducted at 24 weeks (primary endpoint), and 12 and 52 weeks (if feasible). RESULTS: The NMA was informed by five trials reporting FEV1 at 24 weeks. FF/UMEC/VI was statistically significantly more effective at increasing trough FEV1 (based on change from baseline) than all triple comparators in the network apart from UMEC + FF/VI. The NMA was informed by 17 trials reporting moderate or severe exacerbation endpoints. FF/UMEC/VI demonstrated statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus single-inhaler budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR). At 24 weeks, the NMA was informed by five trials. FF/UMEC/VI showed statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus UMEC + FF/VI and BUD/GLY/FOR. FF/UMEC/VI also demonstrated improvements in mean SGRQ score versus other triple therapy comparators at 24 weeks, and a significant reduction in RMU compared with BUD/GLY/FOR (160/18/9.6). CONCLUSION: The findings of this NMA suggest favorable efficacy with single-inhaler triple therapy comprising FF/UMEC/VI. Further analysis is required as additional evidence becomes available.GlaxoSmithKlei

Correction to: Comparative efficacy of Umeclidinium/Vilanterol versus other bronchodilators for the treatment of chronic obstructive pulmonary disease: A network meta-analysis.

This is the final version. Available from Springer via the DOI in this record. The authors regret to inform readers that the labels for the ‘treatment favour’ arrows were incorrectly labelled in Fig. 4. The ‘Favours UMEC/VI 62.5/25’ and ‘Favours comparator’ labels were appended to the wrong arrows and the corrected Fig. 4 is shown below. Please note that the data have not changed between versions

Greater reduction of knee than hip pain in osteoarthritis treated with naproxen, as evaluated by WOMAC and SF‐36

OBJECTIVES: To compare the improvement of hip and knee osteoarthritis during treatment with naproxen. METHODS: Men and women aged 40 to 75 years with symptomatic osteoarthritis of the knee or hip of at least three months' duration participated in a six week placebo controlled, double blind study with naproxen 500 mg twice daily as one treatment arm. Naproxen was given to 403 patients (280 knee, 123 hip) and placebo to 108 patients (75 knee, 33 hip). WOMAC (Western Ontario and McMaster Universities osteoarthritis index) 3.1 visual analogue scale and SF‐36 (36 item short form health survey) were used to assess response to treatment between baseline and week 6. RESULTS: There were no differences at baseline between knee and hip osteoarthritis for any of the WOMAC subscales or SF‐36 domains. Improvement was between 4 and 7 mm greater for knee than for hip for all WOMAC subscales (pain, Δ = 4.7 mm (p = 0.03); stiffness, Δ = 6.6 mm (p = 0.004); function, Δ = 4.8 mm (p = 0.06)). Effect size was about 0.8 for all WOMAC subscales for the knee and between 0.5 and 0.6 for the hip. Knee patients treated with naproxen improved 4.6 (p = 0.033) more than hip patients for SF‐36 bodily pain and 10.3 (p = 0.014) more for SF‐36 role–physical. CONCLUSIONS: Patients with knee osteoarthritis improved more with naproxen treatment than patients with hip osteoarthritis, as monitored by WOMAC and the SF‐36 domains bodily pain and role–physical. These findings warrant further investigation and strongly suggest that efficacy of treatment of osteoarthritis of knee and hip should be evaluated separately