Does the use of inhaled corticosteroids increase the incidence and disease burden of Type 2 Diabetes, osteoporosis or pneumonia compared to non-ICS therapies in patients with Chronic Obstructive Pulmonary Disease.

Date of Approval: 
2016-05-12 00:00:00
Lay Summary: 
Chronic Obstructive Pulmonary Disease (COPD) is a respiratory disease in which patients experience shortness of breath due to narrowing of the airways. One type of drug used as treatment is called a corticosteroid. Due to their anti-inflammatory effects, inhaled corticosteroids (ICS) provide extensive benefit to patients with respiratory diseases associated with an allergic reaction, such as asthma. Medical guidelines for the treatment of COPD suggest that ICS should only be used in patients with moderate to severe disease because studies have revealed these patients receive the most benefit from the drug. Unfortunately, there are numerous adverse effects associated with taking the drug, including oral thrush (a fungal infection), skin bruising and pneumonia. Studies have also found that long term use of ICS in high quantities is associated with increased diagnoses of persistent conditions including Type 2 Diabetes and osteoporosis. Despite the worrying adverse effects associated with ICS treatment, doctors in GP practices in the UK give them to their patients more than guidelines suggest. The aim of this study is to assess the impact of ICS use on Type 2 Diabetes, osteoporosis and pneumonia in a group of patients with COPD in the UK.
Technical Summary: 
The objective is to analyze the relationship between ICS use and Type 2 Diabetes onset, Type 2 Diabetes worsening disease control and disease progression, osteoporosis onset, and incidence of pneumonia. A further objective is to measure overuse of ICS according to guidelines. Firstly, these endpoints will be compared between an ICS therapy cohort and non-ICS therapy cohort. Subsequently, they will be analyzed within the ICS-therapy cohort only and compared by average daily dose, cumulative dose, drug type and inhaler device type. A 1-year baseline period prior to the date of first prescription of ICS therapy or first/additional prescription of non-ICS therapy (i.e. the index date) will be followed by a minimum 1-year outcome period. All of the patient's available data post index date will be utilized. Summary statistics will be produced for unmatched and matched data for all baseline variables by group. Time to event outcomes will be analyzed using multivariable Cox proportional hazards models, reporting hazard ratios with 95% confidence intervals. Continuous progression outcomes will be analyzed using paired t-tests and generalized estimating equations reporting mean changes with 95% confidence intervals. Count outcomes will be analyzed using conditional Poisson regression, reporting incidence rate ratios with 95% confidence intervals.
Health Outcomes to be Measured: 
Type 2 Diabetes onset - is defined in this study as a diagnostic Read code for Type 2 Diabetes, and/or antidiabetic drug prescriptions and/or two or more HbA1c readings > 6.5%. Given the use of Metformin for polycystic ovary syndrome (PCOS), patients with a diagnosis of PCOS and a Metformin prescription will be excluded from the Type 2 Diabetes analysis. Type 2 Diabetes worsening disease control and disease progression - will be analyzed in the group of patients who have a diagnostic Read code for Type 2 Diabetes, and/or antidiabetic drug prescriptions and/or two or more HbA1c readings > 6.5% ever prior to index date. To ensure Metformin prescriptions for treatment of PCOS are not incorrectly counted as incidence of Type 2 Diabetes, patients with PCOS and a Metformin prescription ever prior to index date will be excluded. Worsening disease control will be measured by change in blood glucose level defined as increased glycated haemoglobin (HbA1c) readings. Disease progression will be measured by treatment change. Osteoporosis onset - is defined in this study as a diagnostic Read code for osteoporosis. Osteoporosis drug prescriptions without an accompanying diagnosis code will not be considered indicative of osteoporosis presence given commonly prescribed osteoporosis drugs are prescribed for other conditions and are used for osteopenia. Incidence of pneumonia - is defined as a Read code for pneumonia, with a chest X-ray or hospitalization code within 30 days of pneumonia diagnostic code. In primary care records, chest x-rays and hospitalisations will be identified by Read codes. In secondary care records, ICD-10 codes will be used. A pneumonia code within 4 weeks of the last will be counted as the same case of pneumonia. Overuse of ICS - is defined as ICS drugs prescribed to patients in GOLD groups A and B. Number of patients who are classified as GOLD category A or B with ICS prescriptions will be presented as a proportion of the total number of patients who are classified as GOLD categories A or B.
Application Number: 
16_040
Collaborators: 

David Price - Chief Investigator - OPRI - Observational and Pragmatic Research Institute Pte Ltd
Rosie McDonald - Corresponding Applicant - Research in Real Life ltd.( RiRl )
Andreas Clemens - Collaborator - NOVARTIS
Derek Skinner - Collaborator - Research in Real Life ltd.( RiRl )
Emil Loefroth - Collaborator - NOVARTIS
Jeffrey Stephens - Collaborator - Swansea University
Joan Soriano - Collaborator - Research in Real Life ltd.( RiRl )
Nicolas Roche - Collaborator - University Paris Descartes
Richard Brice - Collaborator - Whitstable Medical Practice
Robert Brett McQueen - Collaborator - Research in Real Life ltd.( RiRl )
Robert Fogel - Collaborator - NOVARTIS
Rupert Jones - Collaborator - Plymouth University

Linkages: 
HES Admitted Patient Care