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FDA Guidance-Designed Study Of The Effects Of Intranasal Triamcinolone Acetonide Aqueous (TAA-AQ) On Growth Velocity (GV) Of Children With Perennial Allergic Rhinitis (PAR)
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FDA Guidance-Designed Study Of The Effects Of Intranasal Triamcinolone Acetonide Aqueous (TAA-AQ) On Growth Velocity (GV) Of Children With Perennial Allergic Rhinitis (PAR) Dr. David P. Skoner, MD; Temple University School of Medicine, Allegheny General Hospital, Pittsburgh, PA; West Penn Allegheny Health System, Pittsburgh, PA. RATIONALE: Earlier studies of GV effects of intranasal corticosteroids (INS) in children with PAR were designed poorly and yielded conflicting results, prompting FDA to publish a guidance on study design. METHODS: Randomized, double-blind, placebo-controlled, parallel-group, multicenter study designed to evaluate the effect of once-daily TAA-AQ nasal spray 110 mg on GV of children with PAR aged 3-9 years, by stadiometry during 4- to 6-month baseline, 12-month treatment, and 2-month follow-up periods. HPA-axis function was measured by urinary cortisol levels. RESULTS: 299 subjects were randomized, and 216 subjects completed the study (107 placebo; 109 TAA-AQ). In the primary analysis (modified ITT: 133 placebo, 134 TAA-AQ), LS mean GV during treatment was lower in the TAA-AQ group than in the placebo group (5.65 cm/year and 6.09 cm/year, respectively). The difference was -0.45 cm/year (95% CI: [-0.78, -0.11], p50.0096). Much of the difference started within the first 2 months of treatment and then stabilized thereafter. In the follow-up period, GV in the TAAAQ group (6.59 cm/year) approached that during baseline (6.70 cm/year), and the placebo group decreased slightly (5.89 cm/year versus 6.06 cm/year during baseline). No clinically-relevant HPA-axis suppression was observed. CONCLUSIONS: This study, using rigorous FDA-recommended design elements, demonstrated that TAA-AQ had a small, statistically significant effect on GV of 3-9 year-old children with PAR. GV effects of all INS should be tested using the same study design.
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Extended Omalizumab Dosage Intervals and Efficacy Dr. Saraleen Benouni, MD1, Dr. Lee E. Sheinkopf, MD, FAAAAI2, Dr. LanAnh T. Do, MD, FAAAAI3, Dr. Asif Rafi, MD2, Dr. Roger M. Katz, MD, FAAAAI2; 1UCLA, Los Angeles, CA, 2 UCLA, Los Angeles, CA, 3UCLA, Los Angeles, CA. RATIONALE: Xolair (Omalizumab) has been marketed for the past 10 years for the treatment of difficult to treat steroid dependent allergic asthma in ages 12-70. We have followed 171 patients on Xolair and report on 40 who have been on Xolair for 3+ years. METHODS: Prospective study and retrospective review of all patients receiving Omalizumab for difficult to treat asthma ages 12-70. RESULTS: 13 of these 40 patients have remained on their original dosing schedules, whereas 27 have increased their dosage intervals from 1 to 16 weeks between injections. The determining factors were base upon improved clinical response and or reduced need for concomitant medications. 11 of 13 patients on the initial protocol have completely reversed to normal FEV1 and/or FEF 25%-75%, and 12 of 27 patients on advanced dosing have reverted to normal FEV1 and/or FEF 25%-75%. Patients between the ages of 13-17 years were able to reverse FEV1 and/or FEF 25%-75% at an average of 15.5 doses(range 10-20), ages 20-40 years by an average of 18 doses (range 12-28), ages 40-50 years by 21.6 (range 12-36) doses, and over 50 years by an average of 26 doses (range 12-36). There were no significant differences noted with respect to gender or pre-treatment IgE levels. CONCLUSIONS: Treatment with Omalizumab is successful in reversing FEV1 and/or FEF 25%-75% by dosage #15 to 26 in many individuals. Younger patients were more likely to reverse. Dosing intervals of Omalizumab can be increased up to every 16 weeks depending on individual responses with reversal and decreased medication usage.
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Effect Of Roflumilast On Asthma Control In Moderate and Severe Asthma Patients Prof. V. A. Beloglazov1, Dr. Yuri Popenko1, Prof. Lawrence M. DuBuske, MD, FAAAAI2; 1Crimean State Medical University, Ukraine, 2George Washington University School of Medicine, DC. RATIONALE: This study investigates the effect of roflumilast as add-on therapy in patients with severe asthma.
METHODS: 80 patients aged from 18 to 60 years old; 36 were males (45%), 44 (55%) - females who received out-patient treatment using high doses of glucocorticosteroids (fluticasone propionate at a dose of 500-1000 mg/day) were studied. Patients were divided into two groups. Group 1 uncontrolled patients with severe asthma (12 subjects; 15%) who received standard treatment according GINA plus roflumilast 500 mg for 1 month; Group 2 uncontrolled severe asthma patients who received standard treatment (68 subjects; 85%). The level of control was assessed by the AsthmaControl Questionnaire (ASQ-Juniper) Severity of symptoms was evaluated using a visual analogue scale with score ranging from 0 points (no symptom) to 6 points (maximally expressed symptom). Spirometry was followed. RESULTS: 2 patients (17%) from Group 1 were withdrawn due to adverse effects (insomnia). In Group 1: controlled disease course was achieved in 2 patients (17%) (0.39 points by ASQ with a 2-fold increase of FEV1); partially controlled course was achieved in 4 patients (33%) (1.35 points according to ASQ with a 1.4-fold increase of FEV1), and no changes were observed in 2 patients. In Group 2: controlled course in 2 subjects (2.94%), partially controlled course in 12 subjects (17.64%) and uncontrolled disease course in 54 subjects (79.4%). CONCLUSIONS: Roflumilast as an adjunctive therapy in patients with uncontrolled severe asthma who have failed high dose inhaled corticosteroids helps to improve asthma control likely by impacting the neutrophilic inflammatory component of the disease.
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The Potent and Selective CRTH2 Antagonist OC000459 Is Effective In The Treatment Of Eosinophilic Asthma When Given Once Daily Dr. Roy Pettipher1, Dr. Michael Perkins1, Dr. Lisa Pearce Collins1, Dr. Mark Baillet2, Dr. Trevor Lewis3, Dr. Jan Steiner4, Prof. John Bell5, Dr. Mark Payton1, Dr. Michael Hunter1; 1Atopix Therapeutics, Abingdon, United Kingdom, 2S-Cubed, Abingdon, United Kingdom, 3TL-Wise Consulting, Cambridge, United Kingdom, 4Oxford Therapeutics Consulting, Brightwell-cum-Sotwell, United Kingdom, 5Medical Sciences Division, Oxford, United Kingdom. RATIONALE: CRTH2 mediates activation of Th2 cells, eosinophils and basophils in response to prostaglandin D2. The CRTH2 antagonist OC000459 reduced airway inflammation and improved lung function in moderate persistent asthma. The current study was conducted to determine whether OC459 was effective when dosed once a day and enabled the definition of the patient phenotype most responsive to treatment. METHODS: Adult subjects (% FEV1 60-85% were randomized to OC000459 (25 mg OD, 200 mg OD or 100 mg BID) or placebo for 12 weeks (n5117-125 per group, Full Analysis Set (FAS)). The primary endpoint was change from baseline in pre-bronchodilator FEV1 and secondary endpoints included ACQ, AQLQ(S), incidence of exacerbations and respiratory infections. Change in FEV1was studied in atopic subjects _250/ml. with blood eosinophilia > RESULTS: The change in FEV1 in the pooled dose groups at endpoint was 95 ml vs placebo (p50.024). In an atopic eosinophilic subgroup, an improvement in FEV1 of 220 ml was observed vs placebo (p50.005). In atopic eeosinophilic subjects aged <40, an increase in FEV1 of 355 ml was seen vs placebo (p50.007). Improvements in ACQ and AQLQ(S) were observed in the FAS and the atopic eosinophilic subgroup. In the FAS there was a lower incidence of exacerbations (3.8% on OC000459 vs 7.7% on placebo, p50.107) and respiratory infections (12.3% on OC000459 vs23.1% on placebo, p50.003) in subjects treated with OC000459. CONCLUSIONS: OC000459 is a safe and effective treatment which achieved clinically meaningful improvements in lung function when dosed once-a-day in allergic asthmatics with an eosinophil-dominant form of the disease.
SATURDAY
Abstracts AB3
J ALLERGY CLIN IMMUNOL VOLUME 133, NUMBER 2
FDA Guidance-Designed Study Of The Effects Of Intranasal Triamcinolone Acetonide Aqueous (TAA-AQ) On Growth Velocity (GV) Of Children With Perennial Allergic Rhinitis (PAR) Dr. David P. Skoner, MD; Temple University School of Medicine, Allegheny General Hospital, Pittsburgh, PA; West Penn Allegheny Health System, Pittsburgh, PA. RATIONALE: Earlier studies of GV effects of intranasal corticosteroids (INS) in children with PAR were designed poorly and yielded conflicting results, prompting FDA to publish a guidance on study design. METHODS: Randomized, double-blind, placebo-controlled, parallel-group, multicenter study designed to evaluate the effect of once-daily TAA-AQ nasal spray 110 mg on GV of children with PAR aged 3-9 years, by stadiometry during 4- to 6-month baseline, 12-month treatment, and 2-month follow-up periods. HPA-axis function was measured by urinary cortisol levels. RESULTS: 299 subjects were randomized, and 216 subjects completed the study (107 placebo; 109 TAA-AQ). In the primary analysis (modified ITT: 133 placebo, 134 TAA-AQ), LS mean GV during treatment was lower in the TAA-AQ group than in the placebo group (5.65 cm/year and 6.09 cm/year, respectively). The difference was -0.45 cm/year (95% CI: [-0.78, -0.11], p50.0096). Much of the difference started within the first 2 months of treatment and then stabilized thereafter. In the follow-up period, GV in the TAAAQ group (6.59 cm/year) approached that during baseline (6.70 cm/year), and the placebo group decreased slightly (5.89 cm/year versus 6.06 cm/year during baseline). No clinically-relevant HPA-axis suppression was observed. CONCLUSIONS: This study, using rigorous FDA-recommended design elements, demonstrated that TAA-AQ had a small, statistically significant effect on GV of 3-9 year-old children with PAR. GV effects of all INS should be tested using the same study design.
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Extended Omalizumab Dosage Intervals and Efficacy Dr. Saraleen Benouni, MD1, Dr. Lee E. Sheinkopf, MD, FAAAAI2, Dr. LanAnh T. Do, MD, FAAAAI3, Dr. Asif Rafi, MD2, Dr. Roger M. Katz, MD, FAAAAI2; 1UCLA, Los Angeles, CA, 2 UCLA, Los Angeles, CA, 3UCLA, Los Angeles, CA. RATIONALE: Xolair (Omalizumab) has been marketed for the past 10 years for the treatment of difficult to treat steroid dependent allergic asthma in ages 12-70. We have followed 171 patients on Xolair and report on 40 who have been on Xolair for 3+ years. METHODS: Prospective study and retrospective review of all patients receiving Omalizumab for difficult to treat asthma ages 12-70. RESULTS: 13 of these 40 patients have remained on their original dosing schedules, whereas 27 have increased their dosage intervals from 1 to 16 weeks between injections. The determining factors were base upon improved clinical response and or reduced need for concomitant medications. 11 of 13 patients on the initial protocol have completely reversed to normal FEV1 and/or FEF 25%-75%, and 12 of 27 patients on advanced dosing have reverted to normal FEV1 and/or FEF 25%-75%. Patients between the ages of 13-17 years were able to reverse FEV1 and/or FEF 25%-75% at an average of 15.5 doses(range 10-20), ages 20-40 years by an average of 18 doses (range 12-28), ages 40-50 years by 21.6 (range 12-36) doses, and over 50 years by an average of 26 doses (range 12-36). There were no significant differences noted with respect to gender or pre-treatment IgE levels. CONCLUSIONS: Treatment with Omalizumab is successful in reversing FEV1 and/or FEF 25%-75% by dosage #15 to 26 in many individuals. Younger patients were more likely to reverse. Dosing intervals of Omalizumab can be increased up to every 16 weeks depending on individual responses with reversal and decreased medication usage.
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Effect Of Roflumilast On Asthma Control In Moderate and Severe Asthma Patients Prof. V. A. Beloglazov1, Dr. Yuri Popenko1, Prof. Lawrence M. DuBuske, MD, FAAAAI2; 1Crimean State Medical University, Ukraine, 2George Washington University School of Medicine, DC. RATIONALE: This study investigates the effect of roflumilast as add-on therapy in patients with severe asthma.
METHODS: 80 patients aged from 18 to 60 years old; 36 were males (45%), 44 (55%) - females who received out-patient treatment using high doses of glucocorticosteroids (fluticasone propionate at a dose of 500-1000 mg/day) were studied. Patients were divided into two groups. Group 1 uncontrolled patients with severe asthma (12 subjects; 15%) who received standard treatment according GINA plus roflumilast 500 mg for 1 month; Group 2 uncontrolled severe asthma patients who received standard treatment (68 subjects; 85%). The level of control was assessed by the AsthmaControl Questionnaire (ASQ-Juniper) Severity of symptoms was evaluated using a visual analogue scale with score ranging from 0 points (no symptom) to 6 points (maximally expressed symptom). Spirometry was followed. RESULTS: 2 patients (17%) from Group 1 were withdrawn due to adverse effects (insomnia). In Group 1: controlled disease course was achieved in 2 patients (17%) (0.39 points by ASQ with a 2-fold increase of FEV1); partially controlled course was achieved in 4 patients (33%) (1.35 points according to ASQ with a 1.4-fold increase of FEV1), and no changes were observed in 2 patients. In Group 2: controlled course in 2 subjects (2.94%), partially controlled course in 12 subjects (17.64%) and uncontrolled disease course in 54 subjects (79.4%). CONCLUSIONS: Roflumilast as an adjunctive therapy in patients with uncontrolled severe asthma who have failed high dose inhaled corticosteroids helps to improve asthma control likely by impacting the neutrophilic inflammatory component of the disease.
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The Potent and Selective CRTH2 Antagonist OC000459 Is Effective In The Treatment Of Eosinophilic Asthma When Given Once Daily Dr. Roy Pettipher1, Dr. Michael Perkins1, Dr. Lisa Pearce Collins1, Dr. Mark Baillet2, Dr. Trevor Lewis3, Dr. Jan Steiner4, Prof. John Bell5, Dr. Mark Payton1, Dr. Michael Hunter1; 1Atopix Therapeutics, Abingdon, United Kingdom, 2S-Cubed, Abingdon, United Kingdom, 3TL-Wise Consulting, Cambridge, United Kingdom, 4Oxford Therapeutics Consulting, Brightwell-cum-Sotwell, United Kingdom, 5Medical Sciences Division, Oxford, United Kingdom. RATIONALE: CRTH2 mediates activation of Th2 cells, eosinophils and basophils in response to prostaglandin D2. The CRTH2 antagonist OC000459 reduced airway inflammation and improved lung function in moderate persistent asthma. The current study was conducted to determine whether OC459 was effective when dosed once a day and enabled the definition of the patient phenotype most responsive to treatment. METHODS: Adult subjects (% FEV1 60-85% were randomized to OC000459 (25 mg OD, 200 mg OD or 100 mg BID) or placebo for 12 weeks (n5117-125 per group, Full Analysis Set (FAS)). The primary endpoint was change from baseline in pre-bronchodilator FEV1 and secondary endpoints included ACQ, AQLQ(S), incidence of exacerbations and respiratory infections. Change in FEV1was studied in atopic subjects _250/ml. with blood eosinophilia > RESULTS: The change in FEV1 in the pooled dose groups at endpoint was 95 ml vs placebo (p50.024). In an atopic eosinophilic subgroup, an improvement in FEV1 of 220 ml was observed vs placebo (p50.005). In atopic eeosinophilic subjects aged <40, an increase in FEV1 of 355 ml was seen vs placebo (p50.007). Improvements in ACQ and AQLQ(S) were observed in the FAS and the atopic eosinophilic subgroup. In the FAS there was a lower incidence of exacerbations (3.8% on OC000459 vs 7.7% on placebo, p50.107) and respiratory infections (12.3% on OC000459 vs23.1% on placebo, p50.003) in subjects treated with OC000459. CONCLUSIONS: OC000459 is a safe and effective treatment which achieved clinically meaningful improvements in lung function when dosed once-a-day in allergic asthmatics with an eosinophil-dominant form of the disease.
SATURDAY
Abstracts AB3
J ALLERGY CLIN IMMUNOL VOLUME 133, NUMBER 2