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CSU) in Three Phase III Studies with Omalizumab
Abstracts AB129
J ALLERGY CLIN IMMUNOL VOLUME 135, NUMBER 2
Clinical Characteristics of Adolescent Patients with Refractory Chronic Idiopathic/Spontaneous Urticaria (CIU/ CSU) in Three Phase III Studies with Omalizumab Stanley Goldstein, MD, FAAAAI1, David P. Skoner, MD2, Benjamin Ortiz, MD3, Farid Kianifard, PhD3, Julie Vu, PharmD4, Meryl Mendelson, MD3; 1Allergy and Asthma Care of Long Island, Rockville Centre, NY, 2 Department of Medicine, Allegheny General Hospital, Pittsburgh, PA, 3 Novartis Pharmaceuticals Corporation, East Hanover, NJ, 4Genentech, Inc., South San Francisco, CA. RATIONALE: Information on the clinical profile of CIU/CSU in adolescents is limited. Baseline characteristics and demographics of an adolescent subgroup of CIU/CSU patients enrolled in randomized, placebo-controlled omalizumab trials are evaluated. METHODS: This is a post-hoc descriptive analysis of pooled baseline data from three omalizumab trials in CIU/CSU patients who remained symptomatic despite H1-antihistamine treatment [and H2-antihistamines and/or leukotriene receptor antagonists (LTRA) in one study]. Demographics and disease characteristics are summarized for overall _12 to <18 years). and for adolescent patients (> RESULTS: Of 975 patients [mean (standard deviation; SD) age, 42.3 (14.1) years], 39 were adolescents [15.1 (1.5) years]. Most patients were female (overall, 73.4%; adolescents, 69.2%) and white (85.4%; 84.6%), with a mean BMI (SD) of 29.6 (7.3) and 24.4 (4.7) kg/m2, respectively. A CU index test (functional anti-FcεR) was positive in 28.5% overall and 17.9% of adolescents. Mean urticaria activity score over 7 days (SD) was 30.9 (6.7) overall and 28.6 (5.7) for adolescents; weekly itch severity score, 14.1 (3.6) and 13.3 (3.4); weekly number of hives score, 16.8 (4.3) and 15.3 (4.0); and Dermatology Life Quality Index overall score, 13.2 (6.5) and 12.0 (5.2), respectively. Overall, patients experienced CIU/ CSU for mean duration (SD) of 6.9 (9.1) years and adolescents for 3.2 (3.7) years, and received 5.0 (2.8) and 4.2 (2.3) previous CIU/CSU medications, respectively. Except for one adult, all patients received antihistamines. Concomitant medications included: H2-receptor antagonists (overall, 48.4%; adolescents, 48.7%); LTRA (34.5%; 35.9%) and steroids (45.7%; 33.3%). CONCLUSIONS: Understanding the clinical profile of CIU/CSU in adolescents will guide clinical practice.
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Use of Omalizumab for Treatment of Antihistamine and Steroid Resistant Chronic Idiopathic Urticaria during Pregnancy Lyda B. Cuervo Pardo, MD1, Maria A. Barcena Blanch, MD2, Cristine Radojicic, MD2; 1Cleveland Clinic Foundation, 2Cleveland Clinic Foundation, Cleveland, OH. RATIONALE: The treatment of antihistamine and steroid resistant Chronic Idiopathic Urticaria (CIU) during pregnancy poses a challenge due to teratogenicity of immunosuppressants. Omalizumab is a recently FDA approved therapy for CIU with pregnancy category B and presents an alternative treatment option. METHODS: We present an initial series of 4 subjects treated for antihistamine and steroid resistant urticaria with Omalizumab who became pregnant during therapy from April 2011 to February 2012 at a tertiary care center. RESULTS: Four women 25-28 years of age initiated on Omalizumab for CIU (300 mg subcutaneously every 28 days) became pregnant and continued therapy throughout their pregnancy. Three patients had a history of asthma demonstrated by pulmonary function tests; two had diagnosis of allergic rhinitis with positive skin testing. All patients were uncontrolled on >3 antihistamines and leukotriene antagonists. 3/4 required immunosuppressive therapy with hydroxychloroquine, dapsone and cyclosporine prior to Omalizumab initiation. All subjects received prednisone and 2/4 required chronic steroid therapy at > 20mg daily without symptomatic improvement. Within the first month of Omalizumab therapy, they reported significant improvement of their symptoms demonstrated by increased hive-free intervals, decreased medical utilization and weaning of steroids.
Subjects had normal prenatal follow ups, full term deliveries and no pregnancy or fetal complications. CONCLUSIONS: There is a significant benefit with treatment of CIU during pregnancy with Omalizumab. With recent FDA approval for this condition, pregnancy category B rating and favorable safety data from the Xolair pregnancy registry (EXPECT), these findings support future strategies for use of Omalizumab for CIU during pregnancy.
415
Use of Tacrolimus in the Management of Refractory Chronic Urticaria Steve M. Dorman, MD1, David A. Khan, MD, FAAAAI2; 1Department of Internal Medicine, Division of Allergy and Immunology, University of Texas Southwestern Medical Center, Dallas, TX, 2University Texas SW Medical Center, Dallas, TX. RATIONALE: Chronic urticaria (CU) causes significant morbidity. Many patients do not achieve adequate control with conventional antihistamine therapy; others require long term corticosteroids, with significant adverse effects. Numerous alternatives have been used including calcineurin inhibitors, primarily cyclosporine. We sought to determine the safety and effectiveness of the calcineurin inhibitor tacrolimus. METHODS: A retrospective chart review was conducted of adult CU patients who were treated with tacrolimus in our allergy clinic. Laboratory values and clinical evidence for toxicity were abstracted as well as physician reports of efficacy. RESULTS: Thirty four adults with CU treated with tacrolimus were identified. Ninety four percent of patients were refractory to both 1st and 2nd generation antihistamines, and 50% were on daily prednisone (mean dose of >20mg/day). Seventy three percent had failed at least 1 alternative medication, including montelukast, sulfasalazine, dapsone, hydroxychloroquine, mycophenolate, colchicine, omalizumaband thyroxine. Mean duration of symptoms prior to starting tacrolimus was 5.7 years. Twenty eight patients (82%) improved with tacrolimus. Sixty one percent were able to discontinue daily prednisone, and 33% were able to decrease prednisone dose by >50%. Twenty of thirty four reported adverse effects, most commonly gastrointestinal symptoms, headache or dysesthesias. Three discontinued tacrolimus because of adverse effects. At least three patients required a second course of tacrolimus due to recurrent CU, and at least two achieved remission with this second course. CONCLUSIONS: Tacrolimus appears to be an effective alternative agent for management of refractory chronic urticaria patients. While adverse effects were common, most were benign, dose-related and infrequently required discontinuation of the drug.
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J ALLERGY CLIN IMMUNOL VOLUME 135, NUMBER 2
Clinical Characteristics of Adolescent Patients with Refractory Chronic Idiopathic/Spontaneous Urticaria (CIU/ CSU) in Three Phase III Studies with Omalizumab Stanley Goldstein, MD, FAAAAI1, David P. Skoner, MD2, Benjamin Ortiz, MD3, Farid Kianifard, PhD3, Julie Vu, PharmD4, Meryl Mendelson, MD3; 1Allergy and Asthma Care of Long Island, Rockville Centre, NY, 2 Department of Medicine, Allegheny General Hospital, Pittsburgh, PA, 3 Novartis Pharmaceuticals Corporation, East Hanover, NJ, 4Genentech, Inc., South San Francisco, CA. RATIONALE: Information on the clinical profile of CIU/CSU in adolescents is limited. Baseline characteristics and demographics of an adolescent subgroup of CIU/CSU patients enrolled in randomized, placebo-controlled omalizumab trials are evaluated. METHODS: This is a post-hoc descriptive analysis of pooled baseline data from three omalizumab trials in CIU/CSU patients who remained symptomatic despite H1-antihistamine treatment [and H2-antihistamines and/or leukotriene receptor antagonists (LTRA) in one study]. Demographics and disease characteristics are summarized for overall _12 to <18 years). and for adolescent patients (> RESULTS: Of 975 patients [mean (standard deviation; SD) age, 42.3 (14.1) years], 39 were adolescents [15.1 (1.5) years]. Most patients were female (overall, 73.4%; adolescents, 69.2%) and white (85.4%; 84.6%), with a mean BMI (SD) of 29.6 (7.3) and 24.4 (4.7) kg/m2, respectively. A CU index test (functional anti-FcεR) was positive in 28.5% overall and 17.9% of adolescents. Mean urticaria activity score over 7 days (SD) was 30.9 (6.7) overall and 28.6 (5.7) for adolescents; weekly itch severity score, 14.1 (3.6) and 13.3 (3.4); weekly number of hives score, 16.8 (4.3) and 15.3 (4.0); and Dermatology Life Quality Index overall score, 13.2 (6.5) and 12.0 (5.2), respectively. Overall, patients experienced CIU/ CSU for mean duration (SD) of 6.9 (9.1) years and adolescents for 3.2 (3.7) years, and received 5.0 (2.8) and 4.2 (2.3) previous CIU/CSU medications, respectively. Except for one adult, all patients received antihistamines. Concomitant medications included: H2-receptor antagonists (overall, 48.4%; adolescents, 48.7%); LTRA (34.5%; 35.9%) and steroids (45.7%; 33.3%). CONCLUSIONS: Understanding the clinical profile of CIU/CSU in adolescents will guide clinical practice.
414
Use of Omalizumab for Treatment of Antihistamine and Steroid Resistant Chronic Idiopathic Urticaria during Pregnancy Lyda B. Cuervo Pardo, MD1, Maria A. Barcena Blanch, MD2, Cristine Radojicic, MD2; 1Cleveland Clinic Foundation, 2Cleveland Clinic Foundation, Cleveland, OH. RATIONALE: The treatment of antihistamine and steroid resistant Chronic Idiopathic Urticaria (CIU) during pregnancy poses a challenge due to teratogenicity of immunosuppressants. Omalizumab is a recently FDA approved therapy for CIU with pregnancy category B and presents an alternative treatment option. METHODS: We present an initial series of 4 subjects treated for antihistamine and steroid resistant urticaria with Omalizumab who became pregnant during therapy from April 2011 to February 2012 at a tertiary care center. RESULTS: Four women 25-28 years of age initiated on Omalizumab for CIU (300 mg subcutaneously every 28 days) became pregnant and continued therapy throughout their pregnancy. Three patients had a history of asthma demonstrated by pulmonary function tests; two had diagnosis of allergic rhinitis with positive skin testing. All patients were uncontrolled on >3 antihistamines and leukotriene antagonists. 3/4 required immunosuppressive therapy with hydroxychloroquine, dapsone and cyclosporine prior to Omalizumab initiation. All subjects received prednisone and 2/4 required chronic steroid therapy at > 20mg daily without symptomatic improvement. Within the first month of Omalizumab therapy, they reported significant improvement of their symptoms demonstrated by increased hive-free intervals, decreased medical utilization and weaning of steroids.
Subjects had normal prenatal follow ups, full term deliveries and no pregnancy or fetal complications. CONCLUSIONS: There is a significant benefit with treatment of CIU during pregnancy with Omalizumab. With recent FDA approval for this condition, pregnancy category B rating and favorable safety data from the Xolair pregnancy registry (EXPECT), these findings support future strategies for use of Omalizumab for CIU during pregnancy.
415
Use of Tacrolimus in the Management of Refractory Chronic Urticaria Steve M. Dorman, MD1, David A. Khan, MD, FAAAAI2; 1Department of Internal Medicine, Division of Allergy and Immunology, University of Texas Southwestern Medical Center, Dallas, TX, 2University Texas SW Medical Center, Dallas, TX. RATIONALE: Chronic urticaria (CU) causes significant morbidity. Many patients do not achieve adequate control with conventional antihistamine therapy; others require long term corticosteroids, with significant adverse effects. Numerous alternatives have been used including calcineurin inhibitors, primarily cyclosporine. We sought to determine the safety and effectiveness of the calcineurin inhibitor tacrolimus. METHODS: A retrospective chart review was conducted of adult CU patients who were treated with tacrolimus in our allergy clinic. Laboratory values and clinical evidence for toxicity were abstracted as well as physician reports of efficacy. RESULTS: Thirty four adults with CU treated with tacrolimus were identified. Ninety four percent of patients were refractory to both 1st and 2nd generation antihistamines, and 50% were on daily prednisone (mean dose of >20mg/day). Seventy three percent had failed at least 1 alternative medication, including montelukast, sulfasalazine, dapsone, hydroxychloroquine, mycophenolate, colchicine, omalizumaband thyroxine. Mean duration of symptoms prior to starting tacrolimus was 5.7 years. Twenty eight patients (82%) improved with tacrolimus. Sixty one percent were able to discontinue daily prednisone, and 33% were able to decrease prednisone dose by >50%. Twenty of thirty four reported adverse effects, most commonly gastrointestinal symptoms, headache or dysesthesias. Three discontinued tacrolimus because of adverse effects. At least three patients required a second course of tacrolimus due to recurrent CU, and at least two achieved remission with this second course. CONCLUSIONS: Tacrolimus appears to be an effective alternative agent for management of refractory chronic urticaria patients. While adverse effects were common, most were benign, dose-related and infrequently required discontinuation of the drug.
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