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Omalizumab, an anti-IgE antibody, significantly reduces emergency visits in patients with severe persistent asthma: A pooled analysis
S76 Abstracts
Omalizumab, an Anti-IgE Antibody, Significantly Reduces Emergency Visits in Patients With Severe Persistent Asthma: A Pooled Analysis P. Korenblat1, E. Meltzer2, W. Busse3, S. Hedgecock4, H. Fox4, M. Blogg4; 1The Clinical Research Center, St Louis, MO, 2Allergy and Asthma Medical Group and Research Center, San Diego, CA, 3University of Wisconsin, Madison, WI, 4Novartis Horsham Research Centre, Horsham, UNITED KINGDOM. RATIONALE: Patients with severe asthma are at high risk of serious exacerbations and asthma-related mortality. The aim of this pooled analysis was to assess the efficacy of add-on omalizumab (Xolair®) therapy on emergency visit rates in patients with severe persistent asthma according to the GINA 2002 classification. METHODS: Data were pooled from 7 controlled trials involving patients with IgE-mediated asthma. Omalizumab was added to current asthma therapy and compared with placebo (in 5 double-blind studies) or with current asthma therapy alone (in 2 open-label studies). The annualized rate of total emergency visits (hospital admissions, emergency room visits and unscheduled doctor visits) were pooled and rate ratios (omalizumab:control) were calculated using the Poisson regression model. RESULTS: The studies included 4308 patients (2511 treated with omalizumab), 93% of whom had severe persistent asthma according to the GINA 2002 classification. Omalizumab had a statistically significant effect compared with control therapy in reducing each type of emergency visit (p<0.05) and for the total emergency visits (p<0.0001). Annualized rates for total emergency visits were 0.332 for omalizumab group and 0.623 for the control group, corresponding to a 47% reduction in total emergency visits with omalizumab. Omalizumab reduced hospital admissions by 52% (p=0.041), emergency room visits by 61% (p=0.013) and unscheduled doctor visits by 47% (p=0.0003). CONCLUSIONS: The results of this pooled analysis indicate that omalizumab add-on therapy significantly reduces emergency visits in patients with severe persistent asthma. Funding: Novartis Pharma AG and Genentech
303
SUNDAY
304
Safety of Semirush Immunotherapy: A Pilot Study
E. Cervantes-Trujano, B. V. Alvarez-Arana, H. E. Guidos-Morales, S. Orozco-Martínez, J. G. Huerta-López; Allergy, Instituto Nacional de Pediatria, México, D.F., MEXICO. RATIONALE: The semi rush immunotherapy (SRI) implies to get top doses of an allergen as soon as possible without adverse reactions. The aim of this study was determinate the safety of different SRI schedules in children METHODS: We include 12 patients with positive skin prick test (SPT) to aeroallergens, distributed in 4 groups attending to the doses of immunotherapy per week (5 time/week, 4 time/week, 3 time/week, 2 time/week). The adverse reactions were classificated in systemic or local. We designed an administration schedule doses starting at 0.1 of 1:10,000 w/v up to 0.2 ml of 1:100w/v. Twenty-three injections were required to get the top dose. Written informed consent was obtained from all participants before enrollment RESULTS: The male: female ratio was 2:1; mean age was 11.6 +/2.1 years. 58.3% of patients presented positive SPT to mites, 16.7% to pollens, 8.3% to animals and 16.7% to mites/pollens. In 58% (7/12) no reaction was documented, 25% (3/12) of patients had a local reaction and 16.7% (2/12) presented systemic reaction (wheezing 48 hours after injection and intense pruritus), epinephrine was not required. In the 3 time/week group no one presented any reaction CONCLUSION: The adverse reaction rate of SRI in children reported by other groups is similar. We documented two cases with mild systemic reaction. All schedules performance in our study were safe but the 3 time/week schedule was the best. Omalizumab Does Not Improve Pulmonary Function or Lessen Medical Therapy in Patients With Mild to Severe Persistent Asthma After 6 Months of Treatment E. Hahn1, M. Vo2, I. Hussain1; 1Allergy and Immunology, Washington University School of Medicine, St.Louis, MO, 2Internal Medicine, New Hanover Regional Medical Center, Wilmington, NC.
305
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
RATIONALE: Trials have shown that treatment with Xolair resulted in improved lung function parameters, decreased symptoms and corticosteroid use. This study evaluates Xolair’s efficacy upon lung function and maintenance treatment in patients with mild to severe persistent asthma. METHODS: Retrospective chart review was completed on 15 adult patients on Xolair therapy, who had mild to severe persistent asthma. Excluded from data analysis were 2 patients who discontinued therapy or did not follow up. They were divided into 2 groups based on subjective assessment of their symptoms. IgE levels were evaluated at baseline. PFTs, concurrent asthma therapies, daily albuterol use, and systemic corticosteroid use were evaluated at baseline and 6 months of treatment. RESULTS: Patients without symptom improvement (n=5) and patients with symptom improvement (n= 8) showed no significant differences in mean baseline FEV1 (p=0.19), IgE levels, and corticosteroid use (p=0.85). Those without symptom improvement did not have a statistical difference between mean baseline and 6 months FEV1 values (61% vs. 66%, p=0.69). Patients with symptom improvement revealed similar results (82% vs.77%, p=0.72). In both groups, oral corticosteroid use was not significantly different between baseline and 6 months of therapy. CONCLUSION: Inconsistent with previous studies, lung function and maintenance corticosteroid use did not change after 6 months of Xolair therapy. Despite therapy length, the benefits of Xolair are not evident in our patients due to small study size and design. Studies evaluating a larger population, longer duration of treatment with Xolair, and prospective controlled design may elucidate the treatment duration needed to observe clinical improvement. Omalizumab Add-on Therapy Significantly Reduces Asthma Exacerbations in Patients With Inadequately Controlled Severe Persistent Asthma Despite GINA 2002 Step 4 Therapy: INNOVATE P. Korenblat1, R. Levy2, R. Slavin3, S. Hedgecock4, H. Fox4, K. Surrey4; 1The Clinical Research Center, St Louis, MO, 2Family Allergy and Asthma Clinic, Atlanta, GA, 3Saint Louis University, St Louis, MO, 4Novartis Horsham Research Centre, Horsham, UNITED KINGDOM. RATIONALE: Patients with inadequately controlled severe persistent asthma despite GINA 2002 step 4 therapy (high-dose inhaled corticosteroids [ICS] plus long-acting 2-agonists [LABA] and additional controller medication if required) are a challenging population with a significant unmet medical need. This study assessed the effect of add-on omalizumab (Xolair®) therapy on asthma exacerbations in this patient population with difficult-to-treat asthma. METHODS: Following run-in, patients (12-75 years) with inadequately controlled asthma despite GINA step 4 therapy with reduced lung function and a recent history of clinically significant exacerbations were randomized to receive omalizumab or placebo for 28 weeks (INNOVATE). The primary efficacy variable was the rate of clinically significant asthma exacerbations (worsening of asthma symptoms requiring systemic corticosteroids) during the 28-week double-blind treatment phase. RESULTS: Of the 482 patients randomized, 419 were included in the efficacy analyses. All patients were receiving ICS plus LABA and twothirds were receiving additional controller medication (including 22% oral corticosteroids). The clinically significant asthma exacerbation rate, adjusted post-hoc for baseline exacerbation history, was 0.68 with omalizumab and 0.91 with placebo during the 28-week treatment phase (26% reduction, p=0.042). Without adjustment, a similar magnitude of effect was seen (19% reduction), but this did not reach statistical significance. Significant improvements compared with placebo were also observed for severe exacerbation rate, emergency visit rate and asthma-related quality of life. CONCLUSIONS: Omalizumab is effective and should be considered as add-on therapy for patients with inadequately controlled severe persistent asthma who have a significant unmet need despite best available therapy. Funding: Novartis Pharma AG and Genentech
306
Omalizumab, an Anti-IgE Antibody, Significantly Reduces Emergency Visits in Patients With Severe Persistent Asthma: A Pooled Analysis P. Korenblat1, E. Meltzer2, W. Busse3, S. Hedgecock4, H. Fox4, M. Blogg4; 1The Clinical Research Center, St Louis, MO, 2Allergy and Asthma Medical Group and Research Center, San Diego, CA, 3University of Wisconsin, Madison, WI, 4Novartis Horsham Research Centre, Horsham, UNITED KINGDOM. RATIONALE: Patients with severe asthma are at high risk of serious exacerbations and asthma-related mortality. The aim of this pooled analysis was to assess the efficacy of add-on omalizumab (Xolair®) therapy on emergency visit rates in patients with severe persistent asthma according to the GINA 2002 classification. METHODS: Data were pooled from 7 controlled trials involving patients with IgE-mediated asthma. Omalizumab was added to current asthma therapy and compared with placebo (in 5 double-blind studies) or with current asthma therapy alone (in 2 open-label studies). The annualized rate of total emergency visits (hospital admissions, emergency room visits and unscheduled doctor visits) were pooled and rate ratios (omalizumab:control) were calculated using the Poisson regression model. RESULTS: The studies included 4308 patients (2511 treated with omalizumab), 93% of whom had severe persistent asthma according to the GINA 2002 classification. Omalizumab had a statistically significant effect compared with control therapy in reducing each type of emergency visit (p<0.05) and for the total emergency visits (p<0.0001). Annualized rates for total emergency visits were 0.332 for omalizumab group and 0.623 for the control group, corresponding to a 47% reduction in total emergency visits with omalizumab. Omalizumab reduced hospital admissions by 52% (p=0.041), emergency room visits by 61% (p=0.013) and unscheduled doctor visits by 47% (p=0.0003). CONCLUSIONS: The results of this pooled analysis indicate that omalizumab add-on therapy significantly reduces emergency visits in patients with severe persistent asthma. Funding: Novartis Pharma AG and Genentech
303
SUNDAY
304
Safety of Semirush Immunotherapy: A Pilot Study
E. Cervantes-Trujano, B. V. Alvarez-Arana, H. E. Guidos-Morales, S. Orozco-Martínez, J. G. Huerta-López; Allergy, Instituto Nacional de Pediatria, México, D.F., MEXICO. RATIONALE: The semi rush immunotherapy (SRI) implies to get top doses of an allergen as soon as possible without adverse reactions. The aim of this study was determinate the safety of different SRI schedules in children METHODS: We include 12 patients with positive skin prick test (SPT) to aeroallergens, distributed in 4 groups attending to the doses of immunotherapy per week (5 time/week, 4 time/week, 3 time/week, 2 time/week). The adverse reactions were classificated in systemic or local. We designed an administration schedule doses starting at 0.1 of 1:10,000 w/v up to 0.2 ml of 1:100w/v. Twenty-three injections were required to get the top dose. Written informed consent was obtained from all participants before enrollment RESULTS: The male: female ratio was 2:1; mean age was 11.6 +/2.1 years. 58.3% of patients presented positive SPT to mites, 16.7% to pollens, 8.3% to animals and 16.7% to mites/pollens. In 58% (7/12) no reaction was documented, 25% (3/12) of patients had a local reaction and 16.7% (2/12) presented systemic reaction (wheezing 48 hours after injection and intense pruritus), epinephrine was not required. In the 3 time/week group no one presented any reaction CONCLUSION: The adverse reaction rate of SRI in children reported by other groups is similar. We documented two cases with mild systemic reaction. All schedules performance in our study were safe but the 3 time/week schedule was the best. Omalizumab Does Not Improve Pulmonary Function or Lessen Medical Therapy in Patients With Mild to Severe Persistent Asthma After 6 Months of Treatment E. Hahn1, M. Vo2, I. Hussain1; 1Allergy and Immunology, Washington University School of Medicine, St.Louis, MO, 2Internal Medicine, New Hanover Regional Medical Center, Wilmington, NC.
305
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
RATIONALE: Trials have shown that treatment with Xolair resulted in improved lung function parameters, decreased symptoms and corticosteroid use. This study evaluates Xolair’s efficacy upon lung function and maintenance treatment in patients with mild to severe persistent asthma. METHODS: Retrospective chart review was completed on 15 adult patients on Xolair therapy, who had mild to severe persistent asthma. Excluded from data analysis were 2 patients who discontinued therapy or did not follow up. They were divided into 2 groups based on subjective assessment of their symptoms. IgE levels were evaluated at baseline. PFTs, concurrent asthma therapies, daily albuterol use, and systemic corticosteroid use were evaluated at baseline and 6 months of treatment. RESULTS: Patients without symptom improvement (n=5) and patients with symptom improvement (n= 8) showed no significant differences in mean baseline FEV1 (p=0.19), IgE levels, and corticosteroid use (p=0.85). Those without symptom improvement did not have a statistical difference between mean baseline and 6 months FEV1 values (61% vs. 66%, p=0.69). Patients with symptom improvement revealed similar results (82% vs.77%, p=0.72). In both groups, oral corticosteroid use was not significantly different between baseline and 6 months of therapy. CONCLUSION: Inconsistent with previous studies, lung function and maintenance corticosteroid use did not change after 6 months of Xolair therapy. Despite therapy length, the benefits of Xolair are not evident in our patients due to small study size and design. Studies evaluating a larger population, longer duration of treatment with Xolair, and prospective controlled design may elucidate the treatment duration needed to observe clinical improvement. Omalizumab Add-on Therapy Significantly Reduces Asthma Exacerbations in Patients With Inadequately Controlled Severe Persistent Asthma Despite GINA 2002 Step 4 Therapy: INNOVATE P. Korenblat1, R. Levy2, R. Slavin3, S. Hedgecock4, H. Fox4, K. Surrey4; 1The Clinical Research Center, St Louis, MO, 2Family Allergy and Asthma Clinic, Atlanta, GA, 3Saint Louis University, St Louis, MO, 4Novartis Horsham Research Centre, Horsham, UNITED KINGDOM. RATIONALE: Patients with inadequately controlled severe persistent asthma despite GINA 2002 step 4 therapy (high-dose inhaled corticosteroids [ICS] plus long-acting 2-agonists [LABA] and additional controller medication if required) are a challenging population with a significant unmet medical need. This study assessed the effect of add-on omalizumab (Xolair®) therapy on asthma exacerbations in this patient population with difficult-to-treat asthma. METHODS: Following run-in, patients (12-75 years) with inadequately controlled asthma despite GINA step 4 therapy with reduced lung function and a recent history of clinically significant exacerbations were randomized to receive omalizumab or placebo for 28 weeks (INNOVATE). The primary efficacy variable was the rate of clinically significant asthma exacerbations (worsening of asthma symptoms requiring systemic corticosteroids) during the 28-week double-blind treatment phase. RESULTS: Of the 482 patients randomized, 419 were included in the efficacy analyses. All patients were receiving ICS plus LABA and twothirds were receiving additional controller medication (including 22% oral corticosteroids). The clinically significant asthma exacerbation rate, adjusted post-hoc for baseline exacerbation history, was 0.68 with omalizumab and 0.91 with placebo during the 28-week treatment phase (26% reduction, p=0.042). Without adjustment, a similar magnitude of effect was seen (19% reduction), but this did not reach statistical significance. Significant improvements compared with placebo were also observed for severe exacerbation rate, emergency visit rate and asthma-related quality of life. CONCLUSIONS: Omalizumab is effective and should be considered as add-on therapy for patients with inadequately controlled severe persistent asthma who have a significant unmet need despite best available therapy. Funding: Novartis Pharma AG and Genentech
306