PURPOSE: A significant percentage of patients with moderate-severe persistent asthma do not achieve guideline-defined asthma control despite combination treatment with inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs). (Bateman, 2004). Omalizumab (OMA) binds serum IgE and reduces asthma exacerbations when added to ICS and ICS/LABAs. We examined the effect of adding OMA on lung function in patients with moderate-severe persistent allergic asthma inadequately controlled with ICS/LABAs.
METHODS: INNOVATE was a 28-week, double-blind, randomized, placebo (PBO)-controlled trial that evaluated OMA in patients taking high-dose ICS (>1000 μg beclomethasone equivalent) and LABAs. The efficacy assessments included change from baseline in FEV1 and investigator global evaluations of treatment effectiveness (IGETE), a 5-point scale ranging from excellent (complete control) to worse (worsening in control). Change in FEV1 was analyzed using analysis of covariance. Responder (IGETE rated excellent/good) vs. non-responder (IGETE rated moderate/poor/worse) rate was analyzed using the Chi-squared test. The Spearman correlation coefficient was computed to examine the association between change from baseline in FEV1 and IGETE.
RESULTS: A total of 419 patients were randomized; 209 to OMA and 210 to PBO. Mean duration of allergic asthma was 23 years. Baseline FEV1 was 60%-80% of predicted in 49% and <60% of predicted in 44% of patients. Overall, mean FEV1 improved by 134 mL vs. 17 mL compared with baseline (least squares means), OMA vs. PBO respectively, p=0.012. 61% of OMA patients compared with 43% of PBO patients (p<0.001) were responders. In OMA responders, mean FEV1 increased 256 mL compared with 90 mL in OMA non-responders. Improvement in FEV1 was associated with better IGETE (Spearman correlation coefficient = −0.21, p<0.001).
CONCLUSION: Addition of OMA significantly improved FEV1 and was rated significantly more effective than placebo in moderate-severe persistent allergic asthmatics inadequately controlled with ICS/LABA combination therapy.
CLINICAL IMPLICATIONS: Addition of omalizumab improves lung function and treatment effectiveness in patients with moderate-severe asthma inadequately controlled with ICS/LABA combination therapy.
DISCLOSURE: Robert Maykut, Employee The authors are employees of Novartis Pharmaceuticals Corporation.