Omalizumab in Adult and Adolescent Patients With Severe Persistent Allergic Asthma

Persistency of response, based on GETE, was dichotomized into responders (excellent or good) and non-responders (moderate, poor or worsening). Persistent responders were patients who were responders at 16 weeks and still at 32 weeks. Persistent non-responders were patients who were non-responders at 16 weeks and still at 32 weeks. Patients were assessed for persistency of response if they were responders at Week 16 and had a second GETE obtained ≥ 4 weeks after the Week 16 assessment or discontinued prematurely for unsatisfactory therapeutic effect ≥ 4 weeks after the Week 16 assessment.

Time frame: Weeks 16 and 32

Population: Modified Intent-to-Treat (mITT) was defined for efficacy analyses which included all randomized patients who had at least one post-baseline efficacy assessment.

Asthma symptoms were evaluated by the Asthma Control Questionnaire (ACQ). The ACQ has six questions to be answered by the patient, each with a 7 point scale (0-good control, 6-poor control), and one question where the actual pre-bronchodilator FEV1 value expressed in % of predicted FEV1 was classified to scores from 0 (\> 95% of predicted) to 6 (\< 50% of predicted). The overall score is the average of the 7 questions; a minimum overall score of 0 = good control of asthma whereas a maximum overall score of 6 = poor control of asthma. A negative change in score indicates improvement in symptoms.

Time frame: Baseline, Week 16, Week 32

Population: mITT with N counts as noted in the category description. To be included in this table patients must have a ACQ measurement for the specified timepoint.

There are 32 questions in the AQLQ and they are in 4 domains (symptoms, activity limitation, emotional function and environmental exposure). Each question was answered on a 7 point scale (1-totally limited/problems all the time, 7-not at all limited/no problems). The overall AQLQ score is the mean of all 32 responses, and the individual domain scores are the means of the items in those domains (a minimum domain / overall score of 1 = Severely impaired whereas a maximum domain / overall score of 7 = not impaired at all). A positive change from baseline score indicates improvement.

Time frame: Baseline, Week 15, Week 31

Population: mITT at Week 15 for OAT + Omalizumab is 214 patients and for OAT is 92 patients; at Week 31 for OAT + Omalizumab is 224 patients and for OAT is 97 patients except as noted in the category description. To be included in this table patients must have a AQLQ measurement for the specified timepoint.

The utility-based EQ-5D questionnaire is in two parts and provides a generic measure of health for clinical and economic appraisal. The first health state classification part has 5 questions each with 3 categories (no problem, moderate problem, severe problems). The second visual analogue scale was measured from 0 (worst imaginable health state) to 100 (best imaginable health state).

Time frame: Baseline, Week 15, Week 31

Population: Modified Intent-to-Treat with N count as noted in category description.

The Work Productivity and Activity Impairment-Allergic Asthma (WPAI-AA) questionnaire measures time missed from work, impairment of work and regular activities within the last 7 days. Questionnaires were administered via phone 1 week prior to the study visit. Outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. Overall work impairment due to asthma problems is derived from the proportion of hours missed from work due to asthma and the degree to which asthma problems affected productivity while working.

Time frame: Baseline and Week 31

Population: Modified Intent-to-Treat. Only patients only who worked and with values at both baseline and Week 31 visit were included. Sensitivity analysis excluded questionnaires which were answered after the clinic visit.

Predicted FEV1 was calculated using the Crapo formula for data at Visit 6 (time of randomization), (MALES: Predicted FEV1 (L) = 0.0414\*height - 0.0244\*age -2.190 and Females: Predicted FEV1 (L) = 0.0342\*height - 0.0255\*age - 1.578, where height is in cm).

Time frame: Weeks 16 and 32

Population: Modified Intent-to-Treat (mITT), for Week 16 N=258/106 for OAT+Omalizumab/OAT and for Week 32 N=266/121 for OAT+Omalizumab/OAT, respectively.

A combined total of unscheduled visits due to asthma exacerbations was calculated for each patient as the total number of hospital admissions, ER visits and unscheduled outpatient clinical visits due to asthma exacerbation. Where more than one type of visit was required on a single day for an asthma exacerbation only the most serious type was included. Where there was more than one visit for a single asthma exacerbation but the visits occurred on different dates, then all were counted.

Time frame: 32 Weeks

Population: Modified Intent-to-Treat (mITT)

Number of participants with persistent response, based on the investigator's GETE, dichotomized to responders (excellent or good) and non-responders (moderate, poor or worsening) for patients receiving omalizumab as add on to optimal asthma therapy, assessed at week 16 and week 32. Persistency was defined as the proportion of responders at 16 weeks who were still responders at 32 weeks. GETE categories are excellent, good, moderate, poor, worsening, and missing as determined by the investigator.

Time frame: Weeks 16 and 32

Population: Modified Intent-to-Treat (mITT)

Number of participants with persistent response, based on the patient's GETE, dichotomized to responders (excellent or good) and non-responders (moderate, poor or worsening) for patients receiving omalizumab as add on to optimal asthma therapy, assessed at week 16 and week 32. Persistency was defined as the proportion of responders at 16 weeks who were still responders at 32 weeks. This is based on the patient's evaluation.

Time frame: Weeks 16 and 32

Population: Modified Intent-to-Treat (mITT)

The type of change for the dose of maintenance systemic steroids could be presented as removal (no more maintenance systemic steroids used), decreased, or maintained.

Time frame: Weeks 16 and 32

Population: mITT patients with systemic steroids at baseline (defined as those patient who used systemic steroids throughout the entire run-in period from Visit 1 to Visit 6).

A clinically significant exacerbation episode was defined as a worsening of asthma requiring treatment with rescue systemic (oral or IV) corticosteroids. The initiation of the rescue systemic corticosteroids marked the start of a clinically significant asthma exacerbation episode and cessation of the rescue systemic corticosteroids regimen marked the end of a clinically significant exacerbation episode. If an exacerbation episode was duplicated, overlapped by at least one day with another episode, or nested within another exacerbation episode, only one exacerbation was counted.

Time frame: 32 Weeks

Population: mITT

Responders were defined as excellent or good based on the investigator's Global Evaluation of Treatment Effectiveness (GETE) for patients receiving omalizumab as add on to optimal asthma therapy, assessed at week 16 and week 32.

Time frame: Weeks 16 and 32

Population: Modified Intent-to-Treat (mITT)

Responders were defined as excellent or good based on the patient's Global Evaluation of Treatment Effectiveness (GETE) for patients receiving omalizumab as add on to optimal asthma therapy, assessed at week 16 and week 32.

Time frame: Weeks 16 and 32

Population: mITT population and patients who were assessed for persistency of response or non-response at Week 16 and had a GETE obtained \>= 4 weeks after the Week 16 assessment or discontinued prematurely or unsatisfactory therapeutic effect \>= 4 weeks after the Week 16 assessment. N=187/28 for OAT+Omalizumab/OAT for responders and N=71/63 for non-responders.

For the subgroup of patients requiring maintenance oral (systemic) corticosteroids throughout the screening period the dose of oral steroid (expressed as prednisolone equivalent dose) at baseline, Week 16 and Week 32 was presented by treatment group, as well as the absolute and percent change from baseline to Weeks 16 and 32. It should be noted that the dose of oral steroid at Weeks 16 and 32 was the dose the patient was maintained on and not the dose to treat an exacerbation if one occurred at that time.

Time frame: Weeks 16 and 32

Population: mITT patients with systemic steriods at baseline (defined as those patient who used systemic steroids throughout the entire run-in period from Visit 1 to Visit 6). N counts as noted in the category description.