Effectiveness of long acting muscarinic-antagonist- (LAMA) as an add-on to inhaled corticosteroids / long acting beta-agonists (LABA) in smoking asthmatics

Date of ISAC Approval: 
17/01/2019
Lay Summary: 
Asthma is a major public health problem in most countries. Strategies to better control this disease must include predisposing factors. One of these factors is smoking and a significant proportion of asthmatics are smokers. Despite the logical expectation that people with asthma would avoid exposure to cigarette smoke, studies suggest that smoking behaviour is prevalent among asthmatics at a rate similar or higher to that found in the general population. Cigarette smoke triggers tightening of the lungs (bronchoconstriction) in asthmatic patients. Smoking asthmatics have more severe breathing problems, worse quality of life and a faster loss of breathing ability compared to non-smoking asthmatics. They are also more likely to have emergency room visits and are at a higher risk of dying following hospitalization for near-fatal asthma events. Despite the importance of smoking as a factor in asthma, clinical trials studying new drugs for asthma generally exclude smokers. We are interested in examining smoking asthma patients' response to specific classes of inhaler drugs called inhaled corticosteroids and if an add-on LAMA therapy results in better treatment of asthma in smokers, which would identify the benefit of add-on therapies in smoking asthmatics that could be addressed by new asthma medications.
Technical Summary: 
The primary Objective is to compare the annualized rate of exacerbation among smoking asthmatics in two cohorts. Cohort I: Patients who had LAMA add-on to FD ICS/LABA and Cohort II: Matched patients who remained on the ICS/LABA regimen. Treatment failure will be defined as increased treatment dose, prescription of additional maintenance therapy, episode of moderate or severe asthma exacerbation or excessive use of short acting beta agonists (SABA). The secondary objectives are to: compare time to exacerbation and annualized rate of exacerbations between medium or high dose ICS/LABA vs medium or high dose ICS/LABA + LAMA add-on; describe the asthma related and all-cause health care resource utilization (HCRU) in the two cohorts; describe SABA use in the two cohorts in the follow-up period.
Health Outcomes to be Measured: 
The annualized rate of exacerbation among smoking asthmatics in two cohorts and between subgroups of these cohorts The time to first exacerbation in smoking asthmatics in two cohorts and between subgroups of these cohorts Health Care Resource Utilization (HCRU) in the two cohorts. SABA use in the two cohorts in the follow-up period.
Collaborators: 

Emil Loefroth - Chief Investigator - NOVARTIS
Amy Cole - Corresponding Applicant - Novartis Ireland Limited
Mr Himanshu Pradhan - Collaborator - Novartis Pharma AG
Hui Cao - Collaborator - NOVARTIS
Mrs Jessica Marvel - Collaborator - Novartis Pharmaceuticals Corporation
Martin McSharry - Collaborator - NOVARTIS
Mr Sibasish Saha - Collaborator - Novartis Pharma AG

Linkages: 
HES A&E;HES Admitted;ONS;Patient IMD;Practice IMD (Standard)