Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines: a randomized, placebo-controlled study
Sarbjit S Saini, Carsten Bindslev-Jensen, Marcus Maurer, Jean-Jacques Grob, Emel Bülbül Baskan, Mary S Bradley, Janice Canvin, Abdelkader Rahmaoui, Panayiotis Georgiou, Oral Alpan, Sheldon Spector, Karin Rosén, Sarbjit S Saini, Carsten Bindslev-Jensen, Marcus Maurer, Jean-Jacques Grob, Emel Bülbül Baskan, Mary S Bradley, Janice Canvin, Abdelkader Rahmaoui, Panayiotis Georgiou, Oral Alpan, Sheldon Spector, Karin Rosén
Abstract
ASTERIA I was a 40-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous omalizumab as add-on therapy for 24 weeks in patients with chronic idiopathic urticaria/spontaneous urticaria (CIU/CSU) who remained symptomatic despite H1 antihistamine treatment at licensed doses. Patients aged 12-75 years with CIU/CSU who remained symptomatic despite treatment with approved doses of H1 antihistamines were randomized (1:1:1:1) in a double-blind manner to subcutaneous omalizumab 75 mg, 150 mg, or 300 mg or placebo every 4 weeks for 24 weeks followed by 16 weeks of follow-up. The primary end point was change from baseline in weekly itch severity score (ISS) at week 12. Among randomized patients (N=319: placebo n=80, omalizumab 75 mg n=78, 150 mg n=80, 300 mg n=81), 262 (82.1%) completed the study. Compared with placebo (n=80), mean weekly ISS was reduced from baseline to week 12 by an additional 2.96 points (95% confidence interval (CI): -4.71 to -1.21; P=0.0010), 2.95 points (95% CI: -4.72 to -1.18; P=0.0012), and 5.80 points (95% CI: -7.49 to -4.10; P<0.0001) in the omalizumab 75-mg (n=77), 150-mg (n=80), and 300-mg groups (n=81), respectively. The omalizumab 300-mg group met all nine secondary end points, including a significant decrease in the duration of time to reach minimally important difference response (⩾5-point decrease) in weekly ISS (P<0.0001) and higher percentages of patients with well-controlled symptoms (urticaria activity score over 7 days (UAS7) ⩽6: 51.9% vs. 11.3%; P<0.0001) and complete response (UAS7=0: 35.8% vs. 8.8%; P<0.0001) versus placebo. During the 24-week treatment period, 2 (2.9%), 3 (3.4%), 0, and 4 (5.0%) patients in the omalizumab 75-mg, 150-mg, 300-mg, and placebo groups, respectively, experienced a serious adverse event. Omalizumab 300 mg administered subcutaneously every 4 weeks reduced weekly ISS and other symptom scores versus placebo in CIU/CSU patients who remained symptomatic despite treatment with approved doses of H1 antihistamines.
Trial registration: ClinicalTrials.gov NCT01287117.
Figures
References
- Asero R. Chronic unremitting urticaria: is the use of antihistamines above the licensed dose effective? A preliminary study of cetirizine at licensed and above-licensed doses. Clin Exp Dermatol. 2007;32:34–8.
- Beck LA, Marcotte GV, MacGlashan D, et al. Omalizumab-induced reductions in mast cell FcɛRI expression and function. J Allergy Clin Immunol. 2004;114:527–30.
- European Medicines Agency 2014. Summary of product characteristics (omalizumab (Xolair)). last accessed 3 April 2014
- Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)–a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994;19:210–6.
- Genentech, Inc. and Novartis Pharmaceuticals Corporation 2014. Xolair (omalizumab) prescribing information. last accessed 3 April 2014
- Gober LM, Sterba PM, Eckman JA, et al. Effect of anti-IgE (omalizumab) in chronic idiopathic urticaria (CIU) patients (abstract) J Allergy Clin Immunol. 2008;121 (suppl 1:S147.
- Kaplan A, Ledford D, Ashby M, et al. Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy. J Allergy Clin Immunol. 2013;132:101–9.
- Kaplan AP, Joseph K, Maykut RJ, et al. Treatment of chronic autoimmune urticaria with omalizumab. J Allergy Clin Immunol. 2008;122:569–73.
- Mathias SD, Dreskin SC, Kaplan A, et al. Development of a daily diary for patients with chronic idiopathic urticaria. Ann Allergy Asthma Immunol. 2010;105:142–8.
- Maurer M, Altrichter S, Bieber T, et al. Efficacy and safety of omalizumab in patients with chronic urticaria who exhibit IgE against thyroperoxidase. J Allergy Clin Immunol. 2011;128:202–9.
- Maurer M, Magerl M, Metz M, et al. Revisions to the international guidelines on the diagnosis and therapy of chronic urticaria. J Dtsch Dermatol Ges. 2013;11:971–978.
- Maurer M, Rosen K, Hsieh HJ, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013;368:924–35.
- Ong YE, Menzies-Gow A, Barkans J, et al. Anti-IgE (omalizumab) inhibits late-phase reactions and inflammatory cells after repeat skin allergen challenge. J Allergy Clin Immunol. 2005;116:558–64.
- Saini S, Rosen KE, Hsieh H-J, et al. A randomized, placebo-controlled, dose-ranging study of single-dose omalizumab in patients with H1-antihistamine–refractory chronic idiopathic urticaria. J Allergy Clin Immunol. 2011;128:567–73.
- Saini SS, MacGlashan D. How IgE upregulates the allergic response. Curr Opin Immunol. 2002;14:694–7.
- Staevska M, Popov TA, Kralimarkova T, et al. The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria. J Allergy Clin Immunol. 2010;125:676–82.
- Tan RA, Corren J. Safety of omalizumab in asthma. Expert Opin Drug Saf. 2011;10:463–71.
- Vonakis BM, Saini SS. New concepts in chronic urticaria. Curr Opin Immunol. 2008;20:709–16.
- Zuberbier T, Asero R, Bindslev-Jensen C, Dermatology Section of the European Academy of Allergology and Clinical Immunology; Global Allergy and Asthma European Network; European Dermatology Forum; World Allergy Organization. et al. EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria. Allergy. 2009;64:1417–1426.
- Zuberbier T, Asero R, Bindslev-Jensen C, Dermatology Section of the European Academy of Allergology and Clinical Immunology; Global Allergy and Asthma European Network; European Dermatology Forum; World Allergy Organization et al. EAACI/GA2LEN/EDF/WAO guideline: management of urticaria. Allergy. 2009;64:1427–1443.
Source: PubMed