Study design
This was a multinational, multicenter, prospective, noninterventional, real-life study conducted in 6 European countries: Austria, Germany, Czech Republic, Hungary, Netherlands, and Ireland. The study ran from February 21, 2018, to April 30, 2019. Ethics approval was obtained according to guidelines and procedures of the respective countries. Physicians who were usually involved in the management of AR and routinely used a visual analog scale (VAS) for symptom assessment in patients with AR were invited to participate in the study. Participating physicians included general practitioners, allergists, otorhinolaryngologists, pulmonologists, dermatologists, and pediatricians.
The study consisted of an inclusion visit (day 0) and a control visit after about 14 days, allowing for some flexibility depending on usual clinical practice. Patients received patient cards at the inclusion visit to record AR symptoms, asthma symptoms, and other outcomes using a VAS. Physicians collected patient cards at the control visit, on or around day 14 or by mail.
Participants
Physicians enrolled patients with moderate-to-severe seasonal or perennial AR according to ARIA criteria, for whom MP-AzeFlu was prescribed for the first time. Decisions to include patients in the study were made by the physicians independently from and after the decision to prescribe MP-AzeFlu to the patient.
Inclusion criteria included first-time prescription of MP-AzeFlu according to the summary of product characteristics, age 12 years or older, moderate-to-severe AR according to ARIA criteria [19], acute symptoms of AR on the day of inclusion (AR symptoms VAS ≥ 50 mm), written informed consent by the patient and (if applicable) caregiver for patients younger than 18 years, ability to understand the instructions for use of MP-AzeFlu according to the summary of product characteristics and patient leaflet, and ability to return the completed patient card.
Exclusion criteria included known allergic reactions to MP-AzeFlu or any of its ingredients, pregnancy or planned pregnancy, breastfeeding, inability to provide informed consent, or missing consent.
Study treatment
All patients received MP-AzeFlu. MP-AzeFlu was dosed as outlined in the country-specific summary of product characteristics: 1 spray in each nostril twice daily (total daily dose: 548 µg azelastine hydrochloride and 200 µg fluticasone propionate) for 2 weeks. Physicians ensured that the patient properly understood the instructions for use, as specified in the summary of product characteristics and patient information leaflet.
Study measures/outcomes
On day 0, the physician documented patient demographics, AR symptoms, and previous treatments of AR in an electronic case report form. Patient recollections of their AR symptoms over the past 24 h were measured using a printed single-line VAS (AR-VAS) in the patient card, ranging from “not at all bothersome” (0 mm) to “extremely bothersome” (100 mm). AR symptom severity VAS scores and, for patients who suffered from asthma, asthma symptom severity VAS scores, were documented on the patient’s card on days 0, 1, 3, 7, and ~ 14. Response was defined as an AR-VAS rating < 50 mm (indicating controlled AR) [20] at least once during the study.
On days 0, 7, and ~ 14, patients assessed their sleep quality and troublesomeness in daily activities over the past 7 days, from “not at all troubled” (0 mm) to “extremely troubled” (100 mm). For patients who suffered from asthma, information on frequency of use of asthma reliever medication was collected at baseline. At the end of the documentation period (day ~ 14), the self-reported change in the frequency of use of asthma reliever medication was recorded as significantly reduced, reduced, equal, increased, or significantly increased. All suspected adverse drug reactions were documented in the case reports.
Statistical methods
Subpopulation analyses were performed for patients with AR but no asthma and for patients with AR and asthma comorbidity. The responder rate was calculated for the study population. Statistical analyses were performed using the statistical software package SAS (SAS Institute Inc.; Cary, NC, USA) version 9.4 or higher.