Characteristics of New Users of Single- and Multiple-Inhaler Triple Therapy for COPD in Primary Care in England.

Purpose: Inhaled triple therapy is recommended for patients with chronic obstructive pulmonary disease (COPD) who have poorly controlled symptoms and to reduce the risk of exacerbations. This study assessed the clinical characteristics of new users of single- and multiple-inhaler triple therapy (SITT and MITT) treated in a primary care setting in England. Patients and Methods: This cross-sectional, observational study used data from an electronic health record database (CPRD Aurum) of COPD patients registered with a primary care practice in England, with linkage to a secondary care database. Patients were required to have initiated a new triple therapy (index) between November 2017 and November 2018 and have ≥12 months of available medical history prior to the index date. Results: In total, 3536 patients initiated fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) SITT for the first time: 65% had a Medical Research Council (MRC) dyspnea score ≥3, 45% had forced expiratory volume in 1 second (FEV1)% predicted <50%, and 64% had a moderate or severe exacerbation in the previous 12 months. The majority (83%) of new FF/UMEC/VI users had a history of MITT use. Immediately prior to FF/UMEC/VI initiation, 46% received MITT, 25% received an inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA), 12% received long-acting muscarinic antagonist (LAMA)/LABA, and 14% stepped up directly from LAMA monotherapy. A second cohort of 6540 patients initiated triple therapy (SITT or MITT) for the first time. COPD severity (airflow limitation, exacerbation history) was worse among patients initiating SITT versus MITT. In the 12 months before triple-therapy initiation, ICS/LABA was the most common treatment; a step up from LAMA/LABA was more common among patients initiating FF/UMEC/VI (34%) or beclomethasone/formoterol/glycopyrronium bromide SITT (25%) than MITT (14%). Conclusion: First-time triple therapy was frequently initiated in patients with COPD inadequately controlled on maintenance therapy. General practitioners in England generally identify appropriate patients who require initiation of triple therapy.

Real-World Treatment Patterns of Multiple-Inhaler Triple Therapy Among Patients with Chronic Obstructive Pulmonary Disease in UK General Practice.

INTRODUCTION: Until recently, triple therapy for chronic obstructive pulmonary disease (COPD) has only been available through treatment with multiple inhalers. Evidence on real-world use of multiple-inhaler triple therapy (MITT), including duration of use and treatment patterns, is limited. METHODS: A retrospective, observational study of electronic health records and hospital episodes in patients with COPD initiating MITT between 2013 and 2015 in the UK was performed. This study described patients initiating, treatment persistence and discontinuation, and prior and subsequent COPD treatments. RESULTS: Eligible patients (N=3825) had a mean age of 69.5 years; most were former or current smokers (95%). The majority (86%) initiated MITT with two inhalers and 14% initiated with three inhalers. Mean duration of use was 5.1 (standard deviation: 4.6) months; 24% of patients persisted for 12 months. Patients who had significantly poorer lung function at baseline (12 months prior to initiating MITT) and had experienced significantly more moderate-to-severe acute exacerbation of COPD (AECOPD) and hospitalizations during the baseline period were more likely to persist for 12 months, compared with those who discontinued within 12 months. Most patients stepped down to an inhaled corticosteroid/long-acting ß2-agonist combination (ICS/LABA; 48%) or a long-acting muscarinic antagonist (LAMA; 45%) after discontinuing MITT. CONCLUSION: Initiation of MITT occurred in patients with clinically relevant symptoms and a history of AECOPD. Persistence varied and was most likely linked to disease severity, although more research is required to fully understand why patients discontinue MITT, the subsequent clinical consequences of therapy discontinuation, and the potential impact of newly available single-inhaler triple therapies.

Interleukin-6 as a potential indicator for prevention of high-risk adenoma recurrence by dietary flavonols in the polyp prevention trial.

Serum interleukin-6 (IL-6), a proinflammatory cytokine, is considered an indicator of inflammation and may be an indicator of colorectal carcinogenesis given that inflammation can promote carcinogenesis. Flavonols, which can be found in fruits and vegetables, may inhibit colorectal carcinogenesis partly by inhibiting inflammation. We estimated odds ratios and 95% confidence intervals (95% CI) to determine whether serum IL-6 was associated with colorectal adenoma recurrence and flavonol intake and thus may serve as a risk indicator and as a response indicator to dietary flavonols. Serum IL-6 concentrations at baseline, year 1, and year 3 were measured in 872 participants from the intervention arm of the Polyp Prevention Trial, a 4-year trial that examined the effectiveness of a low-fat, high-fiber, high-fruit and vegetable diet on adenoma recurrence. Intake of flavonols, especially of isorhamnetin, kaempferol, and quercetin, was inversely associated with serum IL-6 concentrations (highest versus lowest flavonol intake quartile, 1.80 versus 2.20 pg/mL) and high-risk (OR, 0.51; 95% CI, 0.26-0.98) and advanced adenoma recurrence (OR, 0.17; 95% CI, 0.06-0.50). A decrease in IL-6 concentration during the trial was inversely associated with high-risk (OR, 0.44; 95% CI, 0.23-0.84) and advanced adenoma recurrence (OR, 0.47; 95% CI, 0.19-1.18). Individuals with above median flavonol intake and equal or below median IL-6 change after baseline had the lowest risk of recurrence of high-risk and advanced adenoma. Our results suggest that serum IL-6 may serve as a risk indicator and as a response indicator to dietary flavonols for colorectal cancer prevention.