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PREGNANCY REGISTRY DATA

Expect: A Completed Pregnancy Registry for Women with Allergic Asthma Taking XOLAIR4

See the breadth of efficacy data, click here.

 

To date, XOLAIR is the only asthma biologic with a published pregnancy registry analysis in its Prescribing Information4

Risk Summary4
The EXPECT study assessed perinatal outcomes in pregnant women and their infants who were exposed to XOLAIR. The analysis showed no increase in the rate of major birth defects or miscarriage with XOLAIR exposure during pregnancy.

There was an increased rate of low birth weight among registry infants compared to infants in the Quebec External Comparator Cohort (QECC), despite average gestational age at birth; however, women taking XOLAIR during pregnancy also had more severe asthma, which makes it difficult to determine whether the low birth weight was due to the drug or the disease severity.

Study design: EXPECT was a prospective cohort pregnancy exposure registry study conducted from 2006-2018 that included 250 women with asthma who were treated with XOLAIR. Of these, 246 patients were exposed to XOLAIR during the first trimester of pregnancy, and the median exposure duration was 8.7 months.

This analysis compares the final data from the EXPECT registry with findings from the QECC, a disease-matched population of pregnant women with moderate to severe asthma who were not treated with XOLAIR.4,34


The Quebec External Comparator Cohort (QECC)4,33
The registry findings for applicable mother and infant subgroups were compared to age-adjusted frequencies in a disease-matched external cohort. This cohort consisted of 1153 pregnant women with asthma (with no exposure to XOLAIR), who were identified from healthcare databases of residents in the Canadian province of Quebec, and referred to as the Quebec External Comparator Cohort.

246 women received XOLAIR in the
first trimester with a median
exposure of 8.7 months4

246 women received
XOLAIR in the 
first trimester with a
median exposure of 8.7 months4


Study limitations
The registry study could not definitively establish the absence of any risk because of methodological limitations, including the observational nature of the registry, the small sample size, and potential differences between the registry population and the comparator cohort.

Clinical Considerations4
Disease-associated maternal and/or embryo-fetal risk

In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased risk of preeclampsia in the mother. Neonates have an increased risk of prematurity, low birth weight, and being small for gestational age. The level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control.

There are risks associated with poorly or moderately
controlled asthma in pregnancy4

PREVALENCE OF MAJOR CONGENITAL ANOMALIES WAS SIMILAR IN THE 2 GROUPS33

Infants with a major congenital anomaly EXPECT 8.1%, QECC 8.9%.

 

RATES OF LIVE BIRTHS AND LOW BIRTH WEIGHT33

 % live births EXPECT 99.1%, QECC 99.3%. % of live births with low birth weight EXPECT 13.7%, QECC 9.8%.
  • Rates of live births were similar in the 2 groups4,33
  • Rates of low birth weight were higher in the EXPECT cohort4,33

The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.4,33

 

  • Rates of live births were similar in the 2 groups4,34
  • Rates of low birth weight were higher in the EXPECT cohort4,34

The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.4,34


    • Saini SS, Bindslev-Jensen C, Maurer M, et al. Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines: a randomized, placebo-controlled study [published correction appears in J Invest Dermatol. 2015;135(3):925]. J Invest Dermatol. 2015;135(1):67-75.

      Saini SS, Bindslev-Jensen C, Maurer M, et al. Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines: a randomized, placebo-controlled study [published correction appears in J Invest Dermatol. 2015;135(3):925]. J Invest Dermatol. 2015;135(1):67-75.

    • Maurer M, Rosén K, Hsieh H-J, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria [published correction appears in N Engl J Med. 2013;368(24)(suppl):2340-2341]. N Engl J Med. 2013;368(10):924-935.

      Maurer M, Rosén K, Hsieh H-J, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria [published correction appears in N Engl J Med. 2013;368(24)(suppl):2340-2341]. N Engl J Med. 2013;368(10):924-935.

    • Hoskin B, Ortiz B, Paknis B, Kavati A. Exploring the real-world profile of refractory and non-refractory chronic idiopathic urticaria in the USA: clinical burden and healthcare resource use. Curr Med Res Opin. 2019;35(8):1387-1395.

      Hoskin B, Ortiz B, Paknis B, Kavati A. Exploring the real-world profile of refractory and non-refractory chronic idiopathic urticaria in the USA: clinical burden and healthcare resource use. Curr Med Res Opin. 2019;35(8):1387-1395.

    • XOLAIR [prescribing information]. Genentech USA, Inc. and Novartis Pharmaceuticals Corporation.

      XOLAIR [prescribing information]. Genentech USA, Inc. and Novartis Pharmaceuticals Corporation.

    • Maurer M, Weller K, Bindslev-Jensen C, et al. Unmet clinical needs in chronic spontaneous urticaria. A GA2LEN task force report [published online November 17, 2010]. Allergy. 2011;66(3):317​-330. doi:10.1111/j.1398​-9995.2010.02496.x

      Maurer M, Weller K, Bindslev-Jensen C, et al. Unmet clinical needs in chronic spontaneous urticaria. A GA2LEN task force report [published online November 17, 2010]. Allergy. 2011;66(3):317​-330. doi:10.1111/j.1398​-9995.2010.02496.x

    • Grattan CEH. Urticaria and angioedema. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, PA. Elsevier Saunders; 2012;291-306.

      Grattan CEH. Urticaria and angioedema. In: Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, PA. Elsevier Saunders; 2012;291-306.

    • Roche. FDA approves Xolair (omalizumab) for people with chronic idiopathic urticaria, a form of chronic hives. https://www.roche.com/media/releases/med-cor-2020-12-01. March 2014. Accessed January 14, 2021.

      Roche. FDA approves Xolair (omalizumab) for people with chronic idiopathic urticaria, a form of chronic hives. https://www.roche.com/media/releases/med-cor-2020-12-01. March 2014. Accessed January 14, 2021.

    • Data on file. Genentech USA, Inc. South San Francisco, CA.

      Data on file. Genentech USA, Inc. South San Francisco, CA.

    • Zuberbier T, Abdul Latiff AH, Abuzakouk M, et al. The international EAACI/GA2LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria [published online ahead of print, September 18, 2021]. Allergy. 2021;10.1111/all.15090. doi:10.1111/all.15090

      Zuberbier T, Abdul Latiff AH, Abuzakouk M, et al. The international EAACI/GA2LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria [published online ahead of print, September 18, 2021]. Allergy. 2021;10.1111/all.15090. doi:10.1111/all.15090

    • Busse W, Corren J, Lanier BQ, et al. Omalizumab, anti-lgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001;108(2):184-190. doi:10.1067/mai.2001.117880

      Busse W, Corren J, Lanier BQ, et al. Omalizumab, anti-lgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001;108(2):184-190. doi:10.1067/mai.2001.117880

    • Soler M, Matz J, Townley R, et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J. 2001;18(2):254-261.

      Soler M, Matz J, Townley R, et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J. 2001;18(2):254-261.

    • Eguiluz-Gracia I, Layhadi JA, Rondon C, Shamji MH. Mucosal IgE immune responses in respiratory diseases. Curr Opin Pharmacol. 2019;46:100-107.

      Eguiluz-Gracia I, Layhadi JA, Rondon C, Shamji MH. Mucosal IgE immune responses in respiratory diseases. Curr Opin Pharmacol. 2019;46:100-107.

    • Gould HJ, Sutton BJ. IgE in allergy and asthma today. Nat Rev Immunol. 2008;8(3):205-217.

      Gould HJ, Sutton BJ. IgE in allergy and asthma today. Nat Rev Immunol. 2008;8(3):205-217.

    • Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med. 2012;18(5):693-704.

      Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med. 2012;18(5):693-704.

    • Akdis CA, Arkwright PD, Brüggen M-C, et al. Type 2 immunity in the skin and lungs. Allergy. 2020;75(7):1582-1605.

      Akdis CA, Arkwright PD, Brüggen M-C, et al. Type 2 immunity in the skin and lungs. Allergy. 2020;75(7):1582-1605.

    • Tran TN, Zeiger RS, Peters SP, et al. Overlap of atopic, eosinophilic, and TH2-high asthma phenotypes in a general population with current asthma. Ann Allergy Asthma Immunol. 2016;116(1):37-42.

      Tran TN, Zeiger RS, Peters SP, et al. Overlap of atopic, eosinophilic, and TH2-high asthma phenotypes in a general population with current asthma. Ann Allergy Asthma Immunol. 2016;116(1):37-42.

    • Allergens and allergic asthma. Asthma and Allergy Foundation of America. Accessed August 11, 2021. https://www.aafa.org/allergic-asthma/

      Allergens and allergic asthma. Asthma and Allergy Foundation of America. Accessed August 11, 2021. https://www.aafa.org/allergic-asthma/

    • Chipps BE, Zeiger RS, Luskin AT, et al. Baseline asthma burden, comorbidities, and biomarkers in omalizumab-treated patients in PROSPERO. Ann Allergy Asthm Immunol. 2017;119(6):524-532.e2.

      Chipps BE, Zeiger RS, Luskin AT, et al. Baseline asthma burden, comorbidities, and biomarkers in omalizumab-treated patients in PROSPERO. Ann Allergy Asthm Immunol. 2017;119(6):524-532.e2.

    • Ledford DK, Lockey RF. Asthma and comorbidities. Curr Opin Allergy Clin Immunol. 2013;13(1):78-86.

      Ledford DK, Lockey RF. Asthma and comorbidities. Curr Opin Allergy Clin Immunol. 2013;13(1):78-86.

    • Comberiati P, McCormack K, Malka-Rais J, Spahn JD. Proportion of severe asthma patients eligible for mepolizumab therapy by age and age of onset of asthma. J Allergy Clin Immunol Pract. 2019;7(8):2689-2696.e2.

      Comberiati P, McCormack K, Malka-Rais J, Spahn JD. Proportion of severe asthma patients eligible for mepolizumab therapy by age and age of onset of asthma. J Allergy Clin Immunol Pract. 2019;7(8):2689-2696.e2.

    • Castillo JR, Peters SP, Busse WW. Asthma exacerbations: pathogenesis, prevention, and treatment. J Allergy Clin Immunol Pract. 2017;5(4):918-927.

      Castillo JR, Peters SP, Busse WW. Asthma exacerbations: pathogenesis, prevention, and treatment. J Allergy Clin Immunol Pract. 2017;5(4):918-927.

    • Siles RI, Hsieh FH. Allergy blood testing: a practical guide for clinicians. Cleve Clin J Med. 2011;78(9):585-592. doi:10.3949/ccjm.78a.11023

      Siles RI, Hsieh FH. Allergy blood testing: a practical guide for clinicians. Cleve Clin J Med. 2011;78(9):585-592. doi:10.3949/ccjm.78a.11023

    • National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Full Report 2007. Bethesda, MD: National Institutes of Health; 2007. NIH publication 07-4051.

      National Heart, Lung, and Blood Institute. National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Full Report 2007. Bethesda, MD: National Institutes of Health; 2007. NIH publication 07-4051.

    • Bernstein IL, Li JT, Bernstein DI, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. 2008;100(3)(Suppl 3):S1-S148.

      Bernstein IL, Li JT, Bernstein DI, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. 2008;100(3)(Suppl 3):S1-S148.

    • Akar-Ghibril N, Casale T, Custovic A, Phipatanakul W. Allergic endotypes and phenotypes of asthma. J Allergy Clin Immunol Pract. 2020;8:429-440.

      Akar-Ghibril N, Casale T, Custovic A, Phipatanakul W. Allergic endotypes and phenotypes of asthma. J Allergy Clin Immunol Pract. 2020;8:429-440.

    • Sonora Quest Laboratories. Test Interpretation and Management Options—Utilizing ImmunoCAP® KU/L Results. Accessed March 19, 2020. https://www.sonoraquest.com/media/2315/immunocap-ref-range_test-menu_0318.pdf

      Sonora Quest Laboratories. Test Interpretation and Management Options—Utilizing ImmunoCAP® KU/L Results. Accessed March 19, 2020. https://www.sonoraquest.com/media/2315/immunocap-ref-range_test-menu_0318.pdf

    • Kerkhof M, Dubois AE, Postma DS, Schouten JP, de Monchy JG. Role and interpretation of total serum IgE measurements in the diagnosis of allergic airway disease in adults. Allergy. 2003;58(9):905-911.

      Kerkhof M, Dubois AE, Postma DS, Schouten JP, de Monchy JG. Role and interpretation of total serum IgE measurements in the diagnosis of allergic airway disease in adults. Allergy. 2003;58(9):905-911.

    • World Health Organization. Prevention of allergy and allergic asthma. Based on the WHO/WAO meeting on the prevention of allergy and allergic asthma; January 8-9, 2002; Geneva, Switzerland.

      World Health Organization. Prevention of allergy and allergic asthma. Based on the WHO/WAO meeting on the prevention of allergy and allergic asthma; January 8-9, 2002; Geneva, Switzerland.

    • Casale TB, Chipps BE, Rosén K, et al. Response to omalizumab using patient enrichment criteria from trials of novel biologics in asthma. Allergy. 2018;73(2):490-497.

      Casale TB, Chipps BE, Rosén K, et al. Response to omalizumab using patient enrichment criteria from trials of novel biologics in asthma. Allergy. 2018;73(2):490-497.

    • Arbes SJ Jr, Gergen PJ, Vaughn B, Zeldin DC. Asthma cases attributable to atopy: results from the Third National Health and Nutrition Examination Survey. J Allergy Clin Immunol. 2007;120(5):1139-1145.

      Arbes SJ Jr, Gergen PJ, Vaughn B, Zeldin DC. Asthma cases attributable to atopy: results from the Third National Health and Nutrition Examination Survey. J Allergy Clin Immunol. 2007;120(5):1139-1145.

    • Lanier B, Bridges T, Kulus M, Taylor AF, Berhane I, Vidaurre CF. Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. J Allergy Clin Immunol. 2009;124(6):1210-1216.

      Lanier B, Bridges T, Kulus M, Taylor AF, Berhane I, Vidaurre CF. Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. J Allergy Clin Immunol. 2009;124(6):1210-1216.

    • Milgrom H, Fowler-Taylor A, Vidaurre CF, Jayawardene S. Safety and tolerability of omalizumab in children with allergic (IgE-mediated) asthma. Curr Med Res Opin. 2011;27(1):163-169.

      Milgrom H, Fowler-Taylor A, Vidaurre CF, Jayawardene S. Safety and tolerability of omalizumab in children with allergic (IgE-mediated) asthma. Curr Med Res Opin. 2011;27(1):163-169.

    • Namazy JA, Blais L, Andrews EB, et al. Pregnancy outcomes in the omalizumab pregnancy registry and a disease-matched comparator cohort. J Allergy Clin Immunol. 2020;145(2):528-536.e1.

      Namazy JA, Blais L, Andrews EB, et al. Pregnancy outcomes in the omalizumab pregnancy registry and a disease-matched comparator cohort. J Allergy Clin Immunol. 2020;145(2):528-536.e1.

    • Gevaert P, Omachi TA, Corren J, et al. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials [published correction appears in J Allergy Clin Immunol. 2021;147(1):416]. J Allergy Clin Immunol. 2020;146(3):595-605. doi:10.1016/j.jaci.2020.05.032

      Gevaert P, Omachi TA, Corren J, et al. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials [published correction appears in J Allergy Clin Immunol. 2021;147(1):416]. J Allergy Clin Immunol. 2020;146(3):595-605. doi:10.1016/j.jaci.2020.05.032

    • Bachert C, Zhang L, Gevaert P. Current and future treatment options for adult chronic rhinosinusitis: focus on nasal polyposis. J Allergy Clin Immunol. 2015;136(6):1431-1440. doi:10.1016/j.jaci.2015.10.010

      Bachert C, Zhang L, Gevaert P. Current and future treatment options for adult chronic rhinosinusitis: focus on nasal polyposis. J Allergy Clin Immunol. 2015;136(6):1431-1440. doi:10.1016/j.jaci.2015.10.010

    • Hopkins C, Slack R, Lund V, Brown P, Copley L, Browne J. Long-term outcomes from the English national comparative audit of surgery for nasal polyposis and chronic rhinosinusitis. Laryngoscope. 2009;119(12):2459-2465. doi:10.1002/lary.20653

      Hopkins C, Slack R, Lund V, Brown P, Copley L, Browne J. Long-term outcomes from the English national comparative audit of surgery for nasal polyposis and chronic rhinosinusitis. Laryngoscope. 2009;119(12):2459-2465. doi:10.1002/lary.20653

    • DeConde AS, Mace JC, Levy JM, Rudmik L, Alt JA, Smith TL. Prevalence of polyp recurrence after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis. Laryngoscope. 2017;127(3):550-555. doi:10.1002/lary.26391

      DeConde AS, Mace JC, Levy JM, Rudmik L, Alt JA, Smith TL. Prevalence of polyp recurrence after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis. Laryngoscope. 2017;127(3):550-555. doi:10.1002/lary.26391

    • Gevaert P, Calus L, Van Zele T, et al. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol. 2013;131(1):110-6.e1. doi:10.1016/j.jaci.2012.07.047

      Gevaert P, Calus L, Van Zele T, et al. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol. 2013;131(1):110-6.e1. doi:10.1016/j.jaci.2012.07.047

    • Reddel HK, Taylor DR, Bateman ED, et al; American Thoracic Society/European Respiratory Society Task Force on Asthma Control and Exacerbations. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180(1):59-99.

      Reddel HK, Taylor DR, Bateman ED, et al; American Thoracic Society/European Respiratory Society Task Force on Asthma Control and Exacerbations. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180(1):59-99.

    • Zazzali JL, Raimundo K, Trzaskoma B, Rosén KE. Improvements in health-related quality of life from GLACIAL: a phase III, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of omalizumab in patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) receiving concomitant H1 antihistamines, H2 antihistamines, and/or leukotriene receptor antagonist (LTRA) treatment. Poster presented at: the 32nd Anniversary Fall Clinical Dermatology Conference; October 17–20, 2013; Las Vegas, NV.

      Zazzali JL, Raimundo K, Trzaskoma B, Rosén KE. Improvements in health-related quality of life from GLACIAL: a phase III, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of omalizumab in patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) receiving concomitant H1 antihistamines, H2 antihistamines, and/or leukotriene receptor antagonist (LTRA) treatment. Poster presented at: the 32nd Anniversary Fall Clinical Dermatology Conference; October 17–20, 2013; Las Vegas, NV.

    • Finlay AY, Kaplan AP, Beck LA, et al. Omalizumab substantially improves dermatology-related quality of life in patients with chronic spontaneous urticaria. J Eur Acad Dermatol Venereol. 2017;31(10):1715​-1721.

      Finlay AY, Kaplan AP, Beck LA, et al. Omalizumab substantially improves dermatology-related quality of life in patients with chronic spontaneous urticaria. J Eur Acad Dermatol Venereol. 2017;31(10):1715​-1721.

    • Antonova E, Raimundo K, Trzaskoma B, Solari PG, Omachi T, Zazzali JL. Improvement of sleep in patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) treated with omalizumab: results of a randomized, double-blind, placebo-controlled clinical trial (GLACIAL). Poster presented at: the 2014 Annual Scientific Meeting of the American College of Allergy, Asthma & Immunology; November 6–10, 2014; Atlanta, GA.

      Antonova E, Raimundo K, Trzaskoma B, Solari PG, Omachi T, Zazzali JL. Improvement of sleep in patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) treated with omalizumab: results of a randomized, double-blind, placebo-controlled clinical trial (GLACIAL). Poster presented at: the 2014 Annual Scientific Meeting of the American College of Allergy, Asthma & Immunology; November 6–10, 2014; Atlanta, GA.

    • Casale TB, Murphy TR, Holden M, et al. Impact of omalizumab on patient-reported outcomes in chronic idiopathic urticaria: results from XTEND-CIU, a 48-week, randomized, placebo-controlled study. Poster presented at: the American Academy of Allergy, Asthma & Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress; March 2–5, 2018; Orlando, FL.

      Casale TB, Murphy TR, Holden M, et al. Impact of omalizumab on patient-reported outcomes in chronic idiopathic urticaria: results from XTEND-CIU, a 48-week, randomized, placebo-controlled study. Poster presented at: the American Academy of Allergy, Asthma & Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress; March 2–5, 2018; Orlando, FL.

    • Ludmann P. Hives: signs and symptoms. American Academy of Dermatology Association. Updated September 28, 2021. Accessed May 25, 2023. https://www.aad.org/public/diseases/a-z/hives-symptoms

      Ludmann P. Hives: signs and symptoms. American Academy of Dermatology Association. Updated September 28, 2021. Accessed May 25, 2023. https://www.aad.org/public/diseases/a-z/hives-symptoms

    • Hollis K, Proctor C, McBride D, et al. Comparison of Urticaria Activity Score Over 7 Days (UAS7) values obtained from once-daily and twice-daily versions: results from the ASSURE-CSU study. Am J Clin Dermatol. 2018;19(2):267​-274.

      Hollis K, Proctor C, McBride D, et al. Comparison of Urticaria Activity Score Over 7 Days (UAS7) values obtained from once-daily and twice-daily versions: results from the ASSURE-CSU study. Am J Clin Dermatol. 2018;19(2):267​-274.

    IMPORTANT SAFETY INFORMATION

    INDICATION

    XOLAIR® (omalizumab) is indicated for:
    • Adults and pediatric patients 6 years of age and older with moderate to severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids.


      Limitations of Use: XOLAIR is not indicated for the relief of acute bronchospasm or status asthmaticus.

    WARNING: Anaphylaxis

    Anaphylaxis presenting as bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue, has been reported to occur after administration of XOLAIR. Anaphylaxis has occurred as early as after the first dose of XOLAIR, but also has occurred beyond 1 year after beginning regularly administered treatment. Because of the risk of anaphylaxis, initiate XOLAIR therapy in a healthcare setting and closely observe patients for an appropriate period of time after XOLAIR administration. Health care providers administering XOLAIR should be prepared to manage anaphylaxis which can be life-threatening. Inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care should symptoms occur. Selection of patients for self-administration of XOLAIR should be based on criteria to mitigate risk from anaphylaxis.


    CONTRAINDICATIONS

    XOLAIR is contraindicated in patients with a severe hypersensitivity reaction to XOLAIR or to any ingredient of XOLAIR.

    WARNINGS AND PRECAUTIONS

    Anaphylaxis: Anaphylaxis has been reported to occur after administration of XOLAIR in premarketing clinical trials and in postmarketing spontaneous reports. In premarketing clinical trials in patients with asthma, anaphylaxis was reported in 3 of 3507 (0.1%) patients. Anaphylaxis occurred with the first dose of XOLAIR in two patients and with the fourth dose in one patient. The time to onset of anaphylaxis was 90 minutes after administration in two patients and 2 hours after administration in one patient.

    A case-control study in asthma patients showed that, among XOLAIR users, patients with a history of anaphylaxis to foods, medications, or other causes were at increased risk of anaphylaxis associated with XOLAIR, compared to those with no prior history of anaphylaxis.

    In postmarketing spontaneous reports, the frequency of anaphylaxis attributed to XOLAIR use was estimated to be at least 0.2% of patients based on an estimated exposure of about 57,300 patients from June 2003 through December 2006. Approximately 60% to 70% of anaphylaxis cases have been reported to occur within the first three doses of XOLAIR, with additional cases occurring sporadically beyond the third dose.

    Initiate XOLAIR only in a healthcare setting equipped to manage anaphylaxis which can be life-threatening. Observe patients closely for an appropriate period of time after administration of XOLAIR, taking into account the time to onset of anaphylaxis seen in premarketing clinical trials and postmarketing spontaneous reports. Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs or symptoms occur.

    Once XOLAIR therapy has been established, administration of XOLAIR prefilled syringe or autoinjector outside of a healthcare setting by a patient or a caregiver may be appropriate for selected patients. Patient selection, determined by the healthcare provider in consultation with the patient, should take into account the pattern of anaphylaxis events seen in premarketing clinical trials and postmarketing spontaneous reports, as well as individual patient risk factors (e.g. prior history of anaphylaxis), ability to recognize signs and symptoms of anaphylaxis, and ability to perform subcutaneous injections with XOLAIR prefilled syringe or autoinjector with proper technique according to the prescribed dosing regimen and Instructions for Use.

    Discontinue XOLAIR in patients who experience a severe hypersensitivity reaction.

    Malignancy: Malignant neoplasms were observed in 20 of 4127 (0.5%) XOLAIR-treated patients compared with 5 of 2236 (0.2%) control patients in clinical studies of adults and adolescents (≥12 years of age) with asthma and other allergic disorders. The observed malignancies in XOLAIR-treated patients were a variety of types, with breast, non-melanoma skin, prostate, melanoma, and parotid occurring more than once, and five other types occurring once each. The majority of patients were observed for less than 1 year. The impact of longer exposure to XOLAIR or use in patients at higher risk for malignancy (e.g., elderly, current smokers) is not known.

    A subsequent 5-year observational study of 5007 XOLAIR-treated and 2829 non-XOLAIR-treated adolescent and adult patients with moderate to severe persistent asthma and a positive skin test reaction or in vitro reactivity to a perennial aeroallergen found that the incidence rates of primary malignancies (per 1000 patient years) were similar in both groups (12.3 vs 13.0, respectively). Study limitations which include the observational study design, the bias introduced by allowing enrollment of patients previously exposed to XOLAIR (88%), enrollment of patients (56%) while a history of cancer or a premalignant condition were study exclusion criteria, and the high study discontinuation rate (44%) preclude definitively ruling out a malignancy risk with XOLAIR.

    Acute Asthma Symptoms and Deteriorating Disease: XOLAIR has not been shown to alleviate asthma exacerbations acutely. Do not use XOLAIR to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with XOLAIR.

    Corticosteroid Reduction: Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of XOLAIR therapy for asthma. Decrease corticosteroids gradually under the direct supervision of a physician.

    Eosinophilic Conditions: In rare cases, patients with asthma on therapy with XOLAIR may present with serious systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome. These events usually, but not always, have been associated with the reduction of oral corticosteroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between XOLAIR and these underlying conditions has not been established.

    Fever, Arthralgia, and Rash: In post-approval use, some patients have experienced a constellation of signs and symptoms, including arthritis/arthralgia, rash, fever, and lymphadenopathy with an onset 1 to 5 days after the first or subsequent injections of XOLAIR. These signs and symptoms have recurred after additional doses in some patients. Physicians should stop XOLAIR if a patient develops this constellation of signs and symptoms.

    Parasitic (Helminth) Infection: Monitor patients at high risk of geohelminth infection while on XOLAIR therapy. Insufficient data are available to determine the length of monitoring required for geohelminth infections after stopping XOLAIR treatment.

    Laboratory Tests: Due to formation of XOLAIR:IgE complexes, serum total IgE levels increase following administration of XOLAIR and may remain elevated for up to 1 year following discontinuation of XOLAIR. Do not use serum total IgE levels obtained less than 1 year following discontinuation to reassess the dosing regimen for asthma patients, because these levels may not reflect steady state free IgE levels.

    Potential Medication Error Related to Emergency Treatment of Anaphylaxis
    XOLAIR should not be used for the emergency treatment of allergic reactions, including anaphylaxis. In studies to simulate use, some patients and caregivers did not understand that XOLAIR is not intended for the emergency treatment of allergic reactions, including anaphylaxis. The safety and effectiveness of XOLAIR for emergency treatment of allergic reactions, including anaphylaxis, have not been established. Instruct patients that XOLAIR is for maintenance use to reduce allergic reactions, including anaphylaxis, while avoiding food allergens.

    ADVERSE REACTIONS

    Asthma: In patients ≥12 years of age, the most common adverse reactions (≥1% more frequent in XOLAIR-treated patients) were: arthralgia (8%), pain (general) (7%), leg pain (4%), fatigue (3%), dizziness (3%), fracture (2%), arm pain (2%), pruritus (2%), dermatitis (2%), and earache (2%). In pediatric patients 6 to <12 years of age, the most commonly observed adverse reactions (≥3% more frequent in XOLAIR-treated pediatric patients) were: nasopharyngitis, headache, pyrexia, upper abdominal pain, pharyngitis streptococcal, otitis media, viral gastroenteritis, arthropod bite, and epistaxis.

    Injection Site Reactions: In adults and adolescents with asthma, injection site reactions of any severity occurred at a rate of 45% in XOLAIR-treated patients compared with 43% in placebo-treated patients. Severe injection site reactions occurred more frequently in XOLAIR-treated patients compared with patients in the placebo group (12% vs 9%, respectively). The types of injection site reactions in asthma studies included: bruising, redness, warmth, burning, stinging, itching, hive formation, pain, indurations, mass, and inflammation.

    Injection Site Reactions in Healthy Adults: In an open label trial in healthy adults, in which the 300 mg/2 mL autoinjector was compared to the 300 mg/2 mL prefilled syringe, injection site reactions (e.g., induration, pain, erythema, hemorrhage, swelling, discomfort, bruising, hypoesthesia, edema, pruritus) were observed in 24% (16/66) of subjects treated with the autoinjector compared with 14% (9/64) of subjects treated with the prefilled syringe.

    Cardiovascular and Cerebrovascular Events from Clinical Studies in Patients with Asthma: A 5-year observational study was conducted in 5007 XOLAIR-treated and 2829 non-XOLAIR-treated patients ≥12 years of age with moderate to severe persistent asthma and a positive skin test reaction to a perennial aeroallergen to evaluate the long term safety of XOLAIR, including the risk of malignancy. Similar percentages of patients in both cohorts were current (5%) or former smokers (29%). Patients had a mean age of 45 years and were followed for a mean of 3.7 years. More XOLAIR-treated patients were diagnosed with severe asthma (50%) compared to the non-XOLAIR-treated patients (23%). A higher incidence rate (per 1000 patient-years) of overall cardiovascular and cerebrovascular serious adverse events (SAEs) was observed in XOLAIR-treated patients (13.4) compared to non-XOLAIR-treated patients (8.1). Increases in rates were observed for transient ischemic attack (0.7 vs 0.1), myocardial infarction (2.1 vs 0.8), pulmonary hypertension (0.5 vs 0), pulmonary embolism/venous thrombosis (3.2 vs 1.5), and unstable angina (2.2 vs 1.4), while the rates observed for ischemic stroke and cardiovascular death were similar among both study cohorts. The results suggest a potential increased risk of serious cardiovascular and cerebrovascular events in patients treated with XOLAIR, however the observational study design, the inclusion of patients previously exposed to XOLAIR (88% for a mean of 8 months), baseline imbalances in cardiovascular risk factors between the treatment groups, an inability to adjust for unmeasured risk factors, and the high study discontinuation rate (44%) limit the ability to quantify the magnitude of the risk.

    Pregnancy: Data with XOLAIR use in pregnant women are insufficient to inform on drug associated risk.

    You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555 or Novartis Pharmaceuticals Corporation at (888) 669-6682.

    Please see full Prescribing Information, including Boxed WARNING and Medication Guide, for additional Important Safety Information.

    WARNING: Anaphylaxis

    Anaphylaxis presenting as bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue, has been reported to occur after administration of XOLAIR. Anaphylaxis has occurred as early as after the first dose of XOLAIR, but also has occurred beyond 1 year after beginning regularly administered treatment. Because of the risk of anaphylaxis, initiate XOLAIR therapy in a healthcare setting and closely observe patients for an appropriate period of time after XOLAIR administration. Health care providers administering XOLAIR should be prepared to manage anaphylaxis which can be life-threatening. Inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care should symptoms occur. Selection of patients for self-administration of XOLAIR should be based on criteria to mitigate risk from anaphylaxis.

    INDICATION

    XOLAIR® (omalizumab) is indicated for:
    • Adults and pediatric patients 6 years of age and older with moderate to severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids.


      Limitations of Use: XOLAIR is not indicated for the relief of acute bronchospasm or status asthmaticus.


    CONTRAINDICATIONS

    XOLAIR is contraindicated in patients with a severe hypersensitivity reaction to XOLAIR or to any ingredient of XOLAIR.

    WARNINGS AND PRECAUTIONS

    Anaphylaxis: Anaphylaxis has been reported to occur after administration of XOLAIR in premarketing clinical trials and in postmarketing spontaneous reports. In premarketing clinical trials in patients with asthma, anaphylaxis was reported in 3 of 3507 (0.1%) patients. Anaphylaxis occurred with the first dose of XOLAIR in two patients and with the fourth dose in one patient. The time to onset of anaphylaxis was 90 minutes after administration in two patients and 2 hours after administration in one patient.

    A case-control study in asthma patients showed that, among XOLAIR users, patients with a history of anaphylaxis to foods, medications, or other causes were at increased risk of anaphylaxis associated with XOLAIR, compared to those with no prior history of anaphylaxis.

    In postmarketing spontaneous reports, the frequency of anaphylaxis attributed to XOLAIR use was estimated to be at least 0.2% of patients based on an estimated exposure of about 57,300 patients from June 2003 through December 2006. Approximately 60% to 70% of anaphylaxis cases have been reported to occur within the first three doses of XOLAIR, with additional cases occurring sporadically beyond the third dose.

    Initiate XOLAIR only in a healthcare setting equipped to manage anaphylaxis which can be life-threatening. Observe patients closely for an appropriate period of time after administration of XOLAIR, taking into account the time to onset of anaphylaxis seen in premarketing clinical trials and postmarketing spontaneous reports. Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs or symptoms occur.

    Once XOLAIR therapy has been established, administration of XOLAIR prefilled syringe or autoinjector outside of a healthcare setting by a patient or a caregiver may be appropriate for selected patients. Patient selection, determined by the healthcare provider in consultation with the patient, should take into account the pattern of anaphylaxis events seen in premarketing clinical trials and postmarketing spontaneous reports, as well as individual patient risk factors (e.g. prior history of anaphylaxis), ability to recognize signs and symptoms of anaphylaxis, and ability to perform subcutaneous injections with XOLAIR prefilled syringe or autoinjector with proper technique according to the prescribed dosing regimen and Instructions for Use.

    Discontinue XOLAIR in patients who experience a severe hypersensitivity reaction.

    Malignancy: Malignant neoplasms were observed in 20 of 4127 (0.5%) XOLAIR-treated patients compared with 5 of 2236 (0.2%) control patients in clinical studies of adults and adolescents (≥12 years of age) with asthma and other allergic disorders. The observed malignancies in XOLAIR-treated patients were a variety of types, with breast, non-melanoma skin, prostate, melanoma, and parotid occurring more than once, and five other types occurring once each. The majority of patients were observed for less than 1 year. The impact of longer exposure to XOLAIR or use in patients at higher risk for malignancy (e.g., elderly, current smokers) is not known.

    A subsequent 5-year observational study of 5007 XOLAIR-treated and 2829 non-XOLAIR-treated adolescent and adult patients with moderate to severe persistent asthma and a positive skin test reaction or in vitro reactivity to a perennial aeroallergen found that the incidence rates of primary malignancies (per 1000 patient years) were similar in both groups (12.3 vs 13.0, respectively). Study limitations which include the observational study design, the bias introduced by allowing enrollment of patients previously exposed to XOLAIR (88%), enrollment of patients (56%) while a history of cancer or a premalignant condition were study exclusion criteria, and the high study discontinuation rate (44%) preclude definitively ruling out a malignancy risk with XOLAIR.

    Acute Asthma Symptoms and Deteriorating Disease: XOLAIR has not been shown to alleviate asthma exacerbations acutely. Do not use XOLAIR to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with XOLAIR.

    Corticosteroid Reduction: Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of XOLAIR therapy for asthma. Decrease corticosteroids gradually under the direct supervision of a physician.

    Eosinophilic Conditions: In rare cases, patients with asthma on therapy with XOLAIR may present with serious systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome. These events usually, but not always, have been associated with the reduction of oral corticosteroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between XOLAIR and these underlying conditions has not been established.

    Fever, Arthralgia, and Rash: In post-approval use, some patients have experienced a constellation of signs and symptoms, including arthritis/arthralgia, rash, fever, and lymphadenopathy with an onset 1 to 5 days after the first or subsequent injections of XOLAIR. These signs and symptoms have recurred after additional doses in some patients. Physicians should stop XOLAIR if a patient develops this constellation of signs and symptoms.

    Parasitic (Helminth) Infection: Monitor patients at high risk of geohelminth infection while on XOLAIR therapy. Insufficient data are available to determine the length of monitoring required for geohelminth infections after stopping XOLAIR treatment.

    Laboratory Tests: Due to formation of XOLAIR:IgE complexes, serum total IgE levels increase following administration of XOLAIR and may remain elevated for up to 1 year following discontinuation of XOLAIR. Do not use serum total IgE levels obtained less than 1 year following discontinuation to reassess the dosing regimen for asthma patients, because these levels may not reflect steady state free IgE levels.

    Potential Medication Error Related to Emergency Treatment of Anaphylaxis
    XOLAIR should not be used for the emergency treatment of allergic reactions, including anaphylaxis. In studies to simulate use, some patients and caregivers did not understand that XOLAIR is not intended for the emergency treatment of allergic reactions, including anaphylaxis. The safety and effectiveness of XOLAIR for emergency treatment of allergic reactions, including anaphylaxis, have not been established. Instruct patients that XOLAIR is for maintenance use to reduce allergic reactions, including anaphylaxis, while avoiding food allergens.

    ADVERSE REACTIONS

    Asthma: In patients ≥12 years of age, the most common adverse reactions (≥1% more frequent in XOLAIR-treated patients) were: arthralgia (8%), pain (general) (7%), leg pain (4%), fatigue (3%), dizziness (3%), fracture (2%), arm pain (2%), pruritus (2%), dermatitis (2%), and earache (2%). In pediatric patients 6 to <12 years of age, the most commonly observed adverse reactions (≥3% more frequent in XOLAIR-treated pediatric patients) were: nasopharyngitis, headache, pyrexia, upper abdominal pain, pharyngitis streptococcal, otitis media, viral gastroenteritis, arthropod bite, and epistaxis.

    Injection Site Reactions: In adults and adolescents with asthma, injection site reactions of any severity occurred at a rate of 45% in XOLAIR-treated patients compared with 43% in placebo-treated patients. Severe injection site reactions occurred more frequently in XOLAIR-treated patients compared with patients in the placebo group (12% vs 9%, respectively). The types of injection site reactions in asthma studies included: bruising, redness, warmth, burning, stinging, itching, hive formation, pain, indurations, mass, and inflammation.

    Injection Site Reactions in Healthy Adults: In an open label trial in healthy adults, in which the 300 mg/2 mL autoinjector was compared to the 300 mg/2 mL prefilled syringe, injection site reactions (e.g., induration, pain, erythema, hemorrhage, swelling, discomfort, bruising, hypoesthesia, edema, pruritus) were observed in 24% (16/66) of subjects treated with the autoinjector compared with 14% (9/64) of subjects treated with the prefilled syringe.

    Cardiovascular and Cerebrovascular Events from Clinical Studies in Patients with Asthma: A 5-year observational study was conducted in 5007 XOLAIR-treated and 2829 non-XOLAIR-treated patients ≥12 years of age with moderate to severe persistent asthma and a positive skin test reaction to a perennial aeroallergen to evaluate the long term safety of XOLAIR, including the risk of malignancy. Similar percentages of patients in both cohorts were current (5%) or former smokers (29%). Patients had a mean age of 45 years and were followed for a mean of 3.7 years. More XOLAIR-treated patients were diagnosed with severe asthma (50%) compared to the non-XOLAIR-treated patients (23%). A higher incidence rate (per 1000 patient-years) of overall cardiovascular and cerebrovascular serious adverse events (SAEs) was observed in XOLAIR-treated patients (13.4) compared to non-XOLAIR-treated patients (8.1). Increases in rates were observed for transient ischemic attack (0.7 vs 0.1), myocardial infarction (2.1 vs 0.8), pulmonary hypertension (0.5 vs 0), pulmonary embolism/venous thrombosis (3.2 vs 1.5), and unstable angina (2.2 vs 1.4), while the rates observed for ischemic stroke and cardiovascular death were similar among both study cohorts. The results suggest a potential increased risk of serious cardiovascular and cerebrovascular events in patients treated with XOLAIR, however the observational study design, the inclusion of patients previously exposed to XOLAIR (88% for a mean of 8 months), baseline imbalances in cardiovascular risk factors between the treatment groups, an inability to adjust for unmeasured risk factors, and the high study discontinuation rate (44%) limit the ability to quantify the magnitude of the risk.

    Pregnancy: Data with XOLAIR use in pregnant women are insufficient to inform on drug associated risk.

    You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555 or Novartis Pharmaceuticals Corporation at (888) 669-6682.

    Please see full Prescribing Information, including Boxed WARNING and Medication Guide, for additional Important Safety Information.