Evaluation of Dupilumab in Patients With Severe Steroid Dependent Asthma

Percentage reduction of OCS dose was calculated as (optimized OCS dose [mg/day] at baseline - final OCS dose at Week 24)/optimized OCS dose at baseline x 100. Result is presented as Least Squares Mean (Standard Error) percentage reduction from baseline derived from ANCOVA model with missing data multiply imputed.

The Primary Outcome Measure (Percentage Reduction From Baseline in Oral Corticosteroids Dose at Week 24 While Maintaining Asthma Control) is summarized above, as LS Mean (SE). Table below provides a supplementary presentation of the Primary Outcome Measure data; result is presented as median (inter-quartile range). Percentage reduction of OCS dose was calculated as (optimized OCS dose [mg/day] at baseline - final OCS dose at Week 24)/optimized OCS dose at baseline x 100.

Participants were classified according to the binary status of whether or not the 50% OCS dose reduction criterion was achieved at week 24.

Participants were classified according to the binary status of whether or not the reduction of OCS dose to <5 mg/day was achieved at Week 24.

For all participants except those with baseline OCS dose at 35 mg/day, the maximum possible reduction corresponds to reduction to 0 mg/day (no longer requiring OCS). For participants starting with 35 mg/day at baseline, the maximum possible reduction is 32.5 mg/day (i.e. minimum dose per protocol is 2.5 mg).

Participants were classified according to the binary status of whether or not the participant still required OCS at Week 24 while maintaining asthma control.

Absolute reduction was calculated by subtracting Week 24 value from baseline value.

A severe asthma exacerbation event was defined as a deterioration of asthma during the 24-week treatment period requiring: use of systemic corticosteroids for >=3 days (at least double the dose currently used); and/or hospitalization related to asthma symptoms or emergency room visit because of asthma requiring intervention with a systemic corticosteroid treatment. Annualized event rate was the total number of exacerbations that occurred during the treatment period divided by the total number of participant-years treated.

FEV1 was the volume of air exhaled in the first second of a forced expiration as measured by spirometer.

The ACQ-5 has 5 questions, reflecting top-scoring 5 asthma symptoms: woken at night by symptoms, wake in mornings with symptoms, limitation of daily activities, shortness of breath and wheeze. Participants were asked to recall how their asthma had been during previous week and to respond to each of 5 symptom questions on a 7-point scale ranged from 0 (no impairment) to 6 (maximum impairment). ACQ-5 total score was mean of scores of all 5 questions and, therefore, ranged from 0 (totally controlled) to 6 (severely uncontrolled). Higher score indicated lower asthma control.

AQLQ is a disease-specific, self-administered quality of life questionnaire designed to measure functional impairments that were most important to participants with asthma. AQLQ comprised of 32 items in 4 domains: symptoms (12 items), activity limitation (11 items), emotional function (5 items), environmental stimuli (4 items). Each item was scored on a 7-point likert scale (1=maximal impairment, 7=no impairment). The 32 items of the questionnaire were averaged to produce one overall quality of life score ranging from 1 (severely impaired) to 7 (not impaired at all). Higher scores indicate better quality of life.

EQ-5D-5L is a standardized health-related quality of life questionnaire developed by EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state. EQ-5D-5L-VAS records participant's self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable).

The HADS is a general scale to detect states of anxiety and depression already used and validated in asthma, which includes HADS-A and HADS-D subscales. The instrument is comprised of 14 items: 7 related to anxiety (HADS-A) and 7 to depression (HADS-D). Each item on the questionnaire is scored from 0-3. And, the total score is the sum of the scores of the 14 items ranging from 0 (no symptoms) to 42 (severe symptoms), with higher scores indicating higher anxiety/depression complains.

The SNOT-22 is a validated measure of health related quality of life in sino nasal disease. It is a 22 item questionnaire with each item assigned a score ranging from 0-5. The total score may range from 0 (no disease) -110 (worst disease), lower scores represent better health related quality of life.