NEJM | ORIGINAL ARTICLE
Marcus Maurer, M.D., Karin Rosén, M.D., Ph.D., Hsin-Ju Hsieh, Ph.D., Sarbjit Saini, M.D., Clive Grattan, M.D., Ana Gimenéz-Arnau, M.D., Ph.D., Sunil Agarwal, M.D., Ramona Doyle, M.D., Janice Canvin, M.D., Allen Kaplan, M.D., and Thomas Casale, M.D.
N Engl J Med 2013; 368:924-935March 7, 2013DOI: 10.1056/NEJMoa1215372
Many patients with chronic idiopathic urticaria (also called chronic spontaneous urticaria) do not have a response to therapy with H1-antihistamines, even at high doses. In phase 2 trials, omalizumab, an IgE monoclonal antibody that targets IgE and affects mast-cell and basophil function, has shown efficacy in such patients.
In this phase 3, multicenter, randomized, double-blind study, we evaluated the efficacy and safety of omalizumab in patients with moderate-to-severe chronic idiopathic urticaria who remained symptomatic despite H1-antihistamine therapy (licensed doses). We randomly assigned 323 patients to receive three subcutaneous injections, spaced 4 weeks apart, of omalizumab at doses of 75 mg, 150 mg, or 300 mg or placebo, followed by a 16-week observation period. The primary efficacy outcome was the change from baseline in a weekly itch-severity score (ranging from 0 to 21, with higher scores indicating more severe itching).
The baseline weekly itch-severity score was approximately 14 in all four study groups. At week 12, the mean (±SD) change from baseline in the weekly itch-severity score was ?5.1±5.6 in the placebo group, ?5.9±6.5 in the 75-mg group (P=0.46), ?8.1±6.4 in the 150-mg group (P=0.001), and ?9.8±6.0 in the 300-mg group (P<0.001). Most prespecified secondary outcomes at week 12 showed similar dose-dependent effects. The frequency of adverse events was similar across groups. The frequency of serious adverse events was low, although the rate was higher in the 300-mg group (6%) than in the placebo group (3%) or in either the 75-mg or 150-mg group (1% for each).
Omalizumab diminished clinical symptoms and signs of chronic idiopathic urticaria in patients who had remained symptomatic despite the use of approved doses of H1-antihistamines. (Funded by Genentech and Novartis Pharma; ClinicalTrials.gov number, NCT01292473.)
Supported by Genentech and Novartis Pharma.
Dr. Maurer reports receiving consulting fees from Uriach Pharma and UCB, advisory board fees from Uriach Pharma, lecture fees from Sanofi, Merck, FAES, Uriach Pharma, and Almirall, and grant support through his institution from Uriach Pharma; Dr. Rosén, being an employee of Genentech and having an equity interest in Roche; Drs. Hsieh and Doyle, being employees of and having an equity interest in Genentech; Dr. Saini, receiving consulting fees from Array, Kendle, MedImmune, Parmacyclics, and Regeneron; Dr. Gimenéz-Arnau, receiving payment for serving on advisory boards from Uriach Pharma, Almirall, Basilea, and Unilever, payment for expert testimony on Sara Lee products, lecture fees from Bayer-Intendis and Uriach Pharma, payment for the development of educational presentations from Menarini and GlaxoSmithKline, and grant support through her institution from Uriach Pharma, Bayer-Intendis, and Inescop; Dr. Agarwal, being an employee of and having an equity interest in Roche; Dr. Canvin, being an employee of and having an equity interest in Novartis; and Dr. Kaplan, receiving consulting fees from Sanofi-Aventis, lecture fees from Dyax and ViroPharma, and grant support through his institution from Dyax, CSL Behring, and Shire. No other potential conflict of interest relevant to this article was reported.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
This article was published on February 24, 2013, at NEJM.org.
We thank all the clinical staff and patients who participated in the study; Malcolm Greaves for his advice regarding the clinical development program; Dennis Wong and Ed Conner of Genentech for assisting in the design of the study; Jim Zazzali of Genentech for his work developing the electronic diary used by patients; Greg Spaniolo of Genentech for his advice regarding statistical analyses and graphical interpretations; and medical writer Helen Attisha of CircleScience for her assistance in the preparation of the manuscript.
From the Department of Dermatology and Allergy, Charité-Universitätsmedizin, Berlin (M.M.); Genentech, South San Francisco, CA (K.R., H.-J.H., S.A., R.D.); Johns Hopkins Asthma and Allergy Center, Baltimore (S.S.); the Department of Dermatology, Norfolk and Norwich University Hospital, Norwich (C.G.), and Novartis Pharmaceuticals, Horsham, West Sussex (J.C.) — both in the United Kingdom; the Department of Dermatology, Hospital del Mar, Universitat Autònoma, Barcelona (A.G.-A); Medical University of South Carolina, Charleston (A.K.); and Creighton University Medical Center, Omaha, NE (T.C.).
Address reprint requests to Dr. Rosén at Genentech, 1 DNA Way, South San Francisco, CA 94080-4990, or at [email protected]