No Evidence of Off-label Use of Olodaterol and Indacaterol in Denmark, France, and the Netherlands: A Drug Utilization Study

Abstract

To characterize the use of olodaterol and indacaterol in clinical practice and to quantify the off-label use in asthma. Drug utilization study of new users of olodaterol or indacaterol between 2014 and 2017 in the PHARMO Database Network in the Netherlands, the Danish population registers, and the IMS Real-World Evidence Longitudinal Patient Database panels in France. On-label use was defined as use among adults with a recorded diagnosis of COPD. Off-label use was defined as use among adults with a recorded diagnosis of asthma without a recorded diagnosis of COPD or as use among patients aged ≤18 years. Potential off-label use was defined as no recorded diagnosis of either COPD or asthma. The study included 4,158 new users of olodaterol and 9,966 new users of indacaterol. Prevalence of off-label use ranged from 3.5% for both drugs to 12.4% for olodaterol and 11.9% for indacaterol. Prevalence of on-label use ranged from 47.8% to 77.7% for olodaterol and from 28.7% to 70.1% for indacaterol. The remaining new users of olodaterol and indacaterol were classified as potential off-label users, with prevalence ranging from 17.3% to 48.6% for olodaterol and from 20.5% to 66.6% for indacaterol. This study provides no evidence of a major concern in Europe for olodaterol or indacaterol for off-label use in asthma or for pediatric use. Chronic obstructive pulmonary disease (COPD) affects 174 million people worldwide 1. It is a characterized by persistent airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases including smoking 2. Four inhaled long-acting beta2-agonists (LABAs) (salmeterol, formoterol, indacaterol, and olodaterol) are approved for long-term maintenance treatment in patients with COPD. Salmeterol and formoterol are also approved for use in asthma. Olodaterol was first approved in the countries of the European Union since 2013 and is indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD 3. The use of LABAs as monotherapy in asthma without COPD, without a primary anti-inflammatory controller medication, e.g., an inhaled glucocorticosteroid (ICS), has been associated with increased morbidity and mortality 4,5. There were no such concerns if the patient has COPD and concomitant asthma, an overlap of asthma and COPD, or COPD alone. Therefore, the health authorities of the European Union (EU)/European Economic Area Member States requested the conduct of a post-approval drug utilization study to characterize the use of olodaterol in clinical practice and assess the potential off-label use of olodaterol in asthma (see study protocol at EU PAS Register # EUPAS 17386) 6. The main objectives of the study were to describe the baseline characteristics of patients initiating on olodaterol and to quantify off-label use of

Introduction or Discontinuation of Additional Risk Minimisation Measures During the Life Cycle of Medicines in Europe

“…For the discontinuation of aRMMs, the sources of evidence were a non-clinical study (25%) and an observational study (25%). The observational study was a multi-database drug-utilisation study for indacaterol maleate, which was authorised only for use in chronic obstructive pulmonary disease, and had aRMMs to reduce the risks associated with off-label use in asthma; the authors concluded that there was little to no off-label use of indacaterol in the EU [ 10 ]. The data sources could not be identified in two products (50%).…”