Long-term use of fluticasone propionate/salmeterol fixed-dose combination and incidence of nonvertebral fractures among patients with COPD in the UK General Practice Research Database.

INTRODUCTION: There has been inconsistent evidence on the association between use of inhaled corticosteroids (ICS) and increased risk of nonvertebral fractures in patients with asthma or chronic obstructive pulmonary disease (COPD). In a large population-based study in the United Kingdom, we estimated the association between fluticasone propionate/salmeterol fixed-dose combination (FSC) and other ICS use and nonvertebral fracture incidence among patients with COPD. METHODS: We identified a cohort of patients aged ≥ 45 years with COPD in the General Practice Research Database (GPRD) between 2003 and 2006. We used a nested case-control design to estimate the odds of incident nonvertebral fractures associated with prior prescriptions of FSC and other ICS, applying conditional logistic regression and controlling for potential confounders. Exposure to FSC and other ICS was assessed by recency, duration, and number of prescriptions. Average daily dose was defined as low, medium, high, or very high using fluticasone propionate equivalents. RESULTS: We identified 1523 nonvertebral fracture cases among 53 191 patients with COPD at risk in the cohort. Use of FSC in the year prior to the index date was associated with a statistically significant increase in the odds of nonvertebral fractures (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.07-1.47); however, there was no increase in the odds of nonvertebral fractures for other ICS use (OR, 1.12; 95% CI, 0.97-1.30). When examining results by the recent use of prescriptions, an exposure that occurred farther from the index date was associated with a significant increase in nonvertebral fracture (26-52 days prior OR, 1.36; 95% CI, 1.04-1.77; 53-365 days prior OR, 1.39; 95% CI, 1.07-1.78), whereas categories of more recent use (0-12 days prior or 13-25 days prior) were not associated with nonvertebral fractures relative to no FSC use. No pattern of association between increasing levels of FSC or other ICS average daily dose and increased odds of nonvertebral fracture was observed. CONCLUSION: We did not observe a consistent association between prescriptions of FSC or other ICS in terms of recent use or average daily dose in the prior year and increases in the odds of nonvertebral fractures in patients with COPD, although ever use of FSC was associated with a slight elevation in the odds.

Incidence of type 2 diabetes among patients exposed to the combination of pravastatin and paroxetine.

PURPOSE: This study evaluated the effects of concomitant pravastatin and paroxetine use on the incidence of Type 2 Diabetes Mellitus (T2DM). METHODS: A new-user retrospective cohort design was employed using data selected from US health insurance claims databases (OptumInsight and MarketScan) between July 1, 2002, and December 31, 2009. Patients included were of age ≥18; newly prescribed pravastatin or paroxetine; and enrolled in the database for ≥180 days prior to the index date (i.e., first prescription of incident drug). Patients were assigned to either incident pravastatin or incident paroxetine user groups. Patients were followed until the study endpoint (T2DM), discontinuation of incident drug, second drug, or end of study/patient data. Cox proportional hazards models compared T2DM in users of pravastatin who were also taking paroxetine at index the date (combination users) versus pravastatinonly users. A similar analysis among users of paroxetine evaluated the use or non-use of pravastatin at index date. RESULTS: OptumInsight yielded 288,678 incident users of pravastatin or paroxetine; 443,137 were identified in MarketScan. The risk of T2DM among combination users compared to incident pravastatin only users was 1.05 (95% CI: 0.76, 1.44) and 0.94 (95% CI: 0.90, 0.97) in OptumInsight and MarketScan, respectively. The risk of T2DM among combination users compared to incident paroxetine only users was 1.03 (95% CI: 0.69, 1.54) in OptumInsight and 1.02 (95% CI: 0.97, 1.07) in MarketScan. CONCLUSION: The results indicate no increase in the risk of T2DM due to combined use of pravastatin and paroxetine compared to individual use of the two drugs; however, this study is limited by short mean follow-up.

Retapamulin prescriptions and monitored off-label use.

INTRODUCTION: Retapamulin, a topical pleuromutilin that selectively inhibits bacterial protein synthesis, is approved for treatment of impetigo and secondarily infected traumatic lesions in adults and in children older than 9 months of age. OBJECTIVE: A 5-year study was conducted to monitor prescription use in children younger than 9 months of age. METHODS: Annual prescription events were monitored in the UK Clinical Practice Research Datalink (CPRD) and the Clinformatics™ DataMart Multiplan (IMPACT), a product of OptumInsight Life Sciences, Inc. (Eden Prairie, MN, USA), from the USA. RESULTS: In the CPRD, of 148 prescriptions, three (2 %) were identified in children aged less than 9 months between years 2008 and 2011. In IMPACT, of 59,210 claims for retapamulin in children, 1,951 (3.3 %) were categorized as definitive, or uncertain for, less than 9 months of age between 2007 and 2011. CONCLUSION: Retapamulin prescription events in children aged less than 9 months were relatively low compared with other recent estimations of off-label pediatric medicines. Our report provides a framework for future investigations and discussions that may facilitate off-label reporting schemes and promote pediatric drug safety.

Risk of pneumonia with inhaled corticosteroid versus long-acting bronchodilator regimens in chronic obstructive pulmonary disease: a new-user cohort study.

INTRODUCTION: Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD). New-user observational cohort designs may minimize biases associated with previous case-control designs. OBJECTIVE: To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy. METHODS: Pneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting ß2-agonist [LABA] combination) and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional hazards models, with propensity scores to adjust for confounding. SETTING: United Kingdom electronic medical records with linked hospitalization and mortality data (2002-2010). New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up. OUTCOMES: severe pneumonia (primary) and any pneumonia (secondary). RESULTS: Following adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83). Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively. Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use. There was an apparent dose-related effect, with greater risk at higher daily doses of ICS. There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted. CONCLUSIONS: The results of this new-user cohort study are consistent with published findings; ICS were associated with a 20-50% increased risk of pneumonia in COPD, which reduced with exposure time. This risk must be weighed against the benefits when prescribing ICS to patients with COPD.

International variation in medication prescription rates among elderly patients with inflammatory bowel disease.

BACKGROUND AND AIMS: The elderly represent a growing demographic of patients with IBD. No study has previously described variations in care or medication prescriptions in senior patients with IBD. We compared prescription rates among elderly patients with IBD in four countries using health administrative data. METHODS: Databases from the United States (US), United Kingdom (UK), Denmark and Canada were queried. Variation in prescription rates between countries was assessed in patients ≥65y with prevalent IBD who had ≥1 prescription for an IBD-related medication in a given quarter between 2004 and 2009. Patients were identified using previously-reported, validated algorithms. Country-specific rates were compared in each quarter using Fisher's exact test. RESULTS: In patients with Crohn's disease, Canada and US had higher prescription rates for oral 5-ASA (P<0.0001 in all quarters) and infliximab (P<0.05 in 22/24 quarters), while the US had higher rates of thiopurine usage (P<0.05 in 23/24 quarters). Canada had greater rates of methotrexate prescriptions (P<0.05 in 21/24 quarters analyzed). In patients with ulcerative colitis (UC), rates of oral steroid usage was lowest in the US (P<0.05 in 22/24 quarters) and oral 5-ASA use was highest in the US and Canada (P<0.0001 in all quarters). Canada and Denmark used more rectal therapy than the US. Infliximab usage in UC was significantly higher in the US and Canada after 2006. CONCLUSIONS: Significant variation in medication prescription rates exists among countries. Future research should assess whether these differences were associated with disparities in outcomes and health care costs.

Long-term use of fluticasone propionate/salmeterol fixed-dose combination and incidence of cataracts and glaucoma among chronic obstructive pulmonary disease patients in the UK General Practice Research Database.

OBJECTIVES: Some large population-based studies have reported a dose-related increased risk of cataracts and glaucoma associated with use of inhaled corticosteroids (ICS) in patients with asthma or chronic obstructive pulmonary disease (COPD). We evaluated the association between use of ICS-containing products, specifically fluticasone propionate/salmeterol fixed-dose combination (FSC), and incidence of cataracts and glaucoma among patients with COPD in a large electronic medical record database in the United Kingdom. METHODS: We identified a cohort of patients aged 45 years and over with COPD in the General Practice Research Database (GPRD) between 2003 and 2006. Cases of incident cataracts or glaucoma were defined based on diagnosis and procedure codes and matched to controls from the risk set to estimate odds ratios (OR) and 95% confidence intervals (CI). The association with FSC or ICS exposure was modeled using conditional logistic regression. Medication exposure was assessed with respect to recency, duration, and number of prescriptions prior to the index date. Average daily dose was defined as none, low (1-250 mcg), medium (251-500 mcg), high (501-1000 mcg), or very high (1001+ mcg) using fluticasone propionate (FP) equivalents. RESULTS: We identified 2941 incident cataract cases and 327 incident glaucoma cases in the COPD cohort (n = 53,191). FSC or ICS prescriptions were not associated with risk of incident cataracts or glaucoma for any exposure category, after adjusting for confounders. We observed a lack of a dose response in all analyses, where low dose was the reference group. The odds of cataracts associated with FSC dose were medium OR: 1.1 (95% CI: 0.9-1.4); high OR: 1.2 (95% CI: 0.9-1.5); and very high OR: 1.2 (95% CI: 0.9-1.7). The odds of glaucoma associated with FSC dose: medium OR: 1.0 (95% CI: 0.5-2.1); high OR: 1.0 (95% CI: 0.5-2.0); and very high OR: 1.0 (95% CI: 0.4-2.8). CONCLUSIONS: FSC or other ICS exposure was not associated with an increased odds of cataracts or glaucoma, nor was a dose-response relationship observed in this population-based nested case-control study of COPD patients in the United Kingdom.