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Blood Eosinophils and Serum IgE Predict Response to Omalizumab in Patients with Severe Allergic Asthma: Innovate Trial Post-Hoc Analysis
AB16 Abstracts
47
Response to Omalizumab Therapy Based on Level of IgE: A Two Year Observational Study (REALITY Study)
SATURDAY
Jay Peters, MD1, Harjinder Singh, MD2, Yogeet Kaur, MS2, Joseph D. Diaz, MD2; 1Univ. Texas Health Science Center San Antonio, San Antonio, TX, 2Allergy, Asthma and Immunology Associates of South Texas, San Antonio, TX. RATIONALE: Omalizumab is indicated for patients with an IgE level between 30-700 IU/mL, but is often used in patients with levels outside recommendations. Observational study is designed to assess response to anti-IgE therapy based on serum IgE levels, and comparison of response based on physician’s clinical assessment vs objective changes in asthma control. METHODS: Asthmatics patients who have received omalizumab therapy for two years were assessed retrospectively for response. Subjects were grouped by their baseline IgE level: [G1(n580):30-700; G2(n517):7011500; and G3(n526):>1500]. Response rate was identified by two categories: Positive response by Physician’s Global Assessment(PGA), and by Objective Assessment (OA) based on a 50% reduction in at least 3 of the following parameters: asthma exacerbation(AE);steroid-bursts;ERvisits;hospitalizations;increase in FEV1>200cc; and improved ACT _3. All assessments were compared at three time points:16 score> weeks(P1), 1-year(P2), and 2-years(P3). RESULTS: During P1, response-rates were:[G1(54%);G2(71%) and G3(46%)] by PGA and [G1(51%);G2(77%) and G3(62%)] by OA. At one-year(P2), the response-rates were:[G1(81%);G2(94%) and G3(89%)] by PGA and [G1(64%);G2(71%) and G3(89%)] by OA. At 2-year (P2), the response-rates were:[G1(80%);G2(82%) and G3(89%)] by PGA and for OA these were:[G1(69%);G2(71%) and G3(77]. Overall response rate at 1-year and 2-year were 85% and 82 respectively by PGI and 70% and 71% by OA. CONCLUSIONS: Overall, 70 to 80% of subjects treated with omalizumab had a good clinical response independently by both subjective and objective assessments. At both 1 and 2-years after initiation of omalizumab-therapy, the overall response-rate was higher in patients with an IgE level >700 IU/mL than patients within recommended dosing range.
48
Blood Eosinophils and Serum IgE Predict Response to Omalizumab in Patients with Severe Allergic Asthma: Innovate Trial Post-Hoc Analysis
Volkan Manga, MD1, Marc Humbert, MD, PhD2, Ratko Djukanovic3, Steve Greenberg, MD4, Theodore A. Omachi, MD, MBA5, Benjamin Trzaskoma, MS5, Roland Buhl6; 1Novartis Pharma AG, Basel, Switzerland, 2Hospital Antoine Beclere, Unversite Paris-Sud, Clamart, France, 3University of Southampton, Southampton, United Kingdom, 4 Novartis Pharmaceutical Corporation, East Hanover, NJ, 5Genentech, Inc., South San Francisco, CA, 6University Hospital Mainz, Mainz, Germany. RATIONALE: Response to biologic therapy differs among severe allergic asthma (SAA) patients. Biomarker-guided therapy may help to identify subgroups who demonstrate greater clinical benefits from omalizumab than the overall SAA population. METHODS: A post-hoc analysis of INNOVATE trial data (Humbert et al. Allergy 2005) was performed to determine the impact of treatment on exacerbation rates and health-related quality-of-life (AQLQ) of SAA patients stratified by peripheral blood eosinophils per mcl (EOS) and serum IgE (IU/ml). Negative binomial regressions were utilized within biomarker strata to estimate response to omalizumab vs placebo, controlling for potential confounders. RESULTS: An exacerbation reduction was observed among omalizumab_300 (n5245) 38.98%, treated patients vs placebo in EOS-high strata: EOS> _150 (n5316) 39.01%, p50.0178. Exacerbation reducp50.0399; EOS> tion increased further upon enriching these strata according to increased _300/IgE>75 (n5184) 53.88%, p50.0018; IgE (>75 IU/ml): EOS> _150/IgE>75 (n5235) 53.75%, p50.0005. Mean placebo-subtracted EOS>
J ALLERGY CLIN IMMUNOL FEBRUARY 2016
benefits on AQLQ exceeded the minimal clinically-important difference _0.5) and demonstrated statistically significant improvements in both (> _300 (n524) 0.55, p50.0001; EOS> _150 (n5310) EOS-high strata: EOS> _150/ 0.53, p<0.0001. The benefit on AQLQ was most apparent in the EOS> IgE>75 stratum (n5231): 0.59, p<0.0001. CONCLUSIONS: This analysis is among the first to examine a combination of biomarkers to assess response to omalizumab in SAA patients. They suggest that subgroups with a combination of increased IgE and EOS may experience a greater clinical benefit. However, caution must be used in interpreting these results given their post-hoc nature.
49
Steroid Sparing Response with Mepolizumab: Durability of Steroid Reduction in Severe Asthma
Charlene M. Prazma, PhD1, Elisabeth H. Bel, MD, PhD2, Neil C. Barnes, MD3,4, Robert Price5, Frank C. Albers1, Steven W. Yancey6; 1 GlaxoSmithKline, Research Triangle Park, NC, 2University of Amsterdam, Amsterdam, Netherlands, 3GlaxoSmithKline, Uxbridge, United Kingdom, 4The London School of Medicine and Dentistry, London, United Kingdom, 5GlaxoSmithKline, Clinical Statistics, Uxbridge, United Kingdom, 6GlaxoSmithKline, Respiratory Medical Franchise, Research Triangle Park, NC. RATIONALE: Steroid dependent asthma patients are at risk of complications associated with use of oral corticosteroids (OCS). Reduction in dose and duration of OCS use are a major goal for physicians and patients. METHODS: Upon completion of the MENSA or SIRIUS study participants were offered the option to enter MEA115661; a 52-week open-label extension study where all subjects received open-label mepolizumab 100mg administered subcutaneously every 4 weeks as adjunctive therapy. The study objectives were to describe the safety profile of long-term mepolizumab treatment and to evaluate the effects of longterm dosing on clinical markers of asthma control. This post-hoc analysis evaluated the durability of steroid reduction following open-label mepolizumab treatment among the subset of subjects from the SIRIUS study that completed MEA115661. MEA115661 was sponsored by GSK. RESULTS: Ninety-three percent (n5126) of SIRIUS subjects entered the open-label study MEA115661; 65 subjects previously received mepolizumab and 61 subjects previously received placebo, with 57 and 58 subjects completing MEA115661 respectively. For placebo subjects from SIRIUS the median OCS dose achieved at the end of SIRIUS was 10mg/day and following 52 weeks of mepolizumab treatment in MEA115661 was reduced to 5.0mg/day. For subjects who continued mepolizumab the median OCS dose achieved was 2.5mg/day at the end of SIRIUS and was 2.5mg/day at the end of MEA115661. CONCLUSIONS: This open label extension study adds evidence that the steroid reduction achieved in the 24-week double-blind SIRIUS study was sustained. Additionally subjects initiating mepolizumab treatment in MEA115661 demonstrated improvements similar to that seen in SIRIUS.
47
Response to Omalizumab Therapy Based on Level of IgE: A Two Year Observational Study (REALITY Study)
SATURDAY
Jay Peters, MD1, Harjinder Singh, MD2, Yogeet Kaur, MS2, Joseph D. Diaz, MD2; 1Univ. Texas Health Science Center San Antonio, San Antonio, TX, 2Allergy, Asthma and Immunology Associates of South Texas, San Antonio, TX. RATIONALE: Omalizumab is indicated for patients with an IgE level between 30-700 IU/mL, but is often used in patients with levels outside recommendations. Observational study is designed to assess response to anti-IgE therapy based on serum IgE levels, and comparison of response based on physician’s clinical assessment vs objective changes in asthma control. METHODS: Asthmatics patients who have received omalizumab therapy for two years were assessed retrospectively for response. Subjects were grouped by their baseline IgE level: [G1(n580):30-700; G2(n517):7011500; and G3(n526):>1500]. Response rate was identified by two categories: Positive response by Physician’s Global Assessment(PGA), and by Objective Assessment (OA) based on a 50% reduction in at least 3 of the following parameters: asthma exacerbation(AE);steroid-bursts;ERvisits;hospitalizations;increase in FEV1>200cc; and improved ACT _3. All assessments were compared at three time points:16 score> weeks(P1), 1-year(P2), and 2-years(P3). RESULTS: During P1, response-rates were:[G1(54%);G2(71%) and G3(46%)] by PGA and [G1(51%);G2(77%) and G3(62%)] by OA. At one-year(P2), the response-rates were:[G1(81%);G2(94%) and G3(89%)] by PGA and [G1(64%);G2(71%) and G3(89%)] by OA. At 2-year (P2), the response-rates were:[G1(80%);G2(82%) and G3(89%)] by PGA and for OA these were:[G1(69%);G2(71%) and G3(77]. Overall response rate at 1-year and 2-year were 85% and 82 respectively by PGI and 70% and 71% by OA. CONCLUSIONS: Overall, 70 to 80% of subjects treated with omalizumab had a good clinical response independently by both subjective and objective assessments. At both 1 and 2-years after initiation of omalizumab-therapy, the overall response-rate was higher in patients with an IgE level >700 IU/mL than patients within recommended dosing range.
48
Blood Eosinophils and Serum IgE Predict Response to Omalizumab in Patients with Severe Allergic Asthma: Innovate Trial Post-Hoc Analysis
Volkan Manga, MD1, Marc Humbert, MD, PhD2, Ratko Djukanovic3, Steve Greenberg, MD4, Theodore A. Omachi, MD, MBA5, Benjamin Trzaskoma, MS5, Roland Buhl6; 1Novartis Pharma AG, Basel, Switzerland, 2Hospital Antoine Beclere, Unversite Paris-Sud, Clamart, France, 3University of Southampton, Southampton, United Kingdom, 4 Novartis Pharmaceutical Corporation, East Hanover, NJ, 5Genentech, Inc., South San Francisco, CA, 6University Hospital Mainz, Mainz, Germany. RATIONALE: Response to biologic therapy differs among severe allergic asthma (SAA) patients. Biomarker-guided therapy may help to identify subgroups who demonstrate greater clinical benefits from omalizumab than the overall SAA population. METHODS: A post-hoc analysis of INNOVATE trial data (Humbert et al. Allergy 2005) was performed to determine the impact of treatment on exacerbation rates and health-related quality-of-life (AQLQ) of SAA patients stratified by peripheral blood eosinophils per mcl (EOS) and serum IgE (IU/ml). Negative binomial regressions were utilized within biomarker strata to estimate response to omalizumab vs placebo, controlling for potential confounders. RESULTS: An exacerbation reduction was observed among omalizumab_300 (n5245) 38.98%, treated patients vs placebo in EOS-high strata: EOS> _150 (n5316) 39.01%, p50.0178. Exacerbation reducp50.0399; EOS> tion increased further upon enriching these strata according to increased _300/IgE>75 (n5184) 53.88%, p50.0018; IgE (>75 IU/ml): EOS> _150/IgE>75 (n5235) 53.75%, p50.0005. Mean placebo-subtracted EOS>
J ALLERGY CLIN IMMUNOL FEBRUARY 2016
benefits on AQLQ exceeded the minimal clinically-important difference _0.5) and demonstrated statistically significant improvements in both (> _300 (n524) 0.55, p50.0001; EOS> _150 (n5310) EOS-high strata: EOS> _150/ 0.53, p<0.0001. The benefit on AQLQ was most apparent in the EOS> IgE>75 stratum (n5231): 0.59, p<0.0001. CONCLUSIONS: This analysis is among the first to examine a combination of biomarkers to assess response to omalizumab in SAA patients. They suggest that subgroups with a combination of increased IgE and EOS may experience a greater clinical benefit. However, caution must be used in interpreting these results given their post-hoc nature.
49
Steroid Sparing Response with Mepolizumab: Durability of Steroid Reduction in Severe Asthma
Charlene M. Prazma, PhD1, Elisabeth H. Bel, MD, PhD2, Neil C. Barnes, MD3,4, Robert Price5, Frank C. Albers1, Steven W. Yancey6; 1 GlaxoSmithKline, Research Triangle Park, NC, 2University of Amsterdam, Amsterdam, Netherlands, 3GlaxoSmithKline, Uxbridge, United Kingdom, 4The London School of Medicine and Dentistry, London, United Kingdom, 5GlaxoSmithKline, Clinical Statistics, Uxbridge, United Kingdom, 6GlaxoSmithKline, Respiratory Medical Franchise, Research Triangle Park, NC. RATIONALE: Steroid dependent asthma patients are at risk of complications associated with use of oral corticosteroids (OCS). Reduction in dose and duration of OCS use are a major goal for physicians and patients. METHODS: Upon completion of the MENSA or SIRIUS study participants were offered the option to enter MEA115661; a 52-week open-label extension study where all subjects received open-label mepolizumab 100mg administered subcutaneously every 4 weeks as adjunctive therapy. The study objectives were to describe the safety profile of long-term mepolizumab treatment and to evaluate the effects of longterm dosing on clinical markers of asthma control. This post-hoc analysis evaluated the durability of steroid reduction following open-label mepolizumab treatment among the subset of subjects from the SIRIUS study that completed MEA115661. MEA115661 was sponsored by GSK. RESULTS: Ninety-three percent (n5126) of SIRIUS subjects entered the open-label study MEA115661; 65 subjects previously received mepolizumab and 61 subjects previously received placebo, with 57 and 58 subjects completing MEA115661 respectively. For placebo subjects from SIRIUS the median OCS dose achieved at the end of SIRIUS was 10mg/day and following 52 weeks of mepolizumab treatment in MEA115661 was reduced to 5.0mg/day. For subjects who continued mepolizumab the median OCS dose achieved was 2.5mg/day at the end of SIRIUS and was 2.5mg/day at the end of MEA115661. CONCLUSIONS: This open label extension study adds evidence that the steroid reduction achieved in the 24-week double-blind SIRIUS study was sustained. Additionally subjects initiating mepolizumab treatment in MEA115661 demonstrated improvements similar to that seen in SIRIUS.