BERLIN — Omalizumab proved effective and safe in patients with moderate to severe chronic urticaria refractory to antihistamines in a double-blind, placebo-controlled, multicenter trial.
Seventy percent of omalizumab-treated participants were free of all symptoms at 27 weeks, compared with 4.5% of placebo-treated controls.
“For those of you who know urticaria and know how well drugs do in urticaria patients, I think this is absolutely amazing. There's no other drug that can do this. Your favorite antihistamine can't achieve these levels. Plus, these are patients who've already been on pretty much everything else and didn't respond,” Dr. Marcus Maurer said at the annual congress of the European Academy of Dermatology and Venereology.
“This is definitely a drug to consider when you have patients who do not respond to your standard urticaria treatment,” added Dr. Maurer, a dermatologist at Charité University Hospital, Berlin.
Omalizumab (Xolair, Genentech/Novartis) is a monoclonal antibody directed against IgE that is approved for treatment of severe allergic asthma. It binds to IgE, preventing it from binding to the IgE receptor on mast cells.
For their proof-of-concept study, Dr. Maurer and coworkers restricted eligibility to patients with one specific subtype of urticaria, autoallergic. These are patients with IgE antibodies directed to thyroid peroxidase as an autoantigen.
A total of 27 patients were randomized to omalizumab and 22 to placebo. Two subjects in the omalizumab arm dropped out during the study period, as did five in the control group, mainly due to lack of response.
Mean baseline score on an urticaria assessment scale was 25 out of a possible 42. At 6 months the score in the omalizumab group had dropped to 6, while remaining unchanged in the control group. The omalizumab group also made significantly less use of rescue antihistamines.
Response to omalizumab occurred rapidly, within the first several weeks. “It's very different from asthma patients, who take a couple of months to respond,” Dr. Maurer said.
There were no omalizumab-related safety issues. “We know that anti-IgE has a very good safety profile from the thousands of asthma patients treated with this drug,” he said.
Xolair is indicated in the United States for treating adults and adolescents aged 12 years and older with moderate to severe persistent asthma. In 2007, the Food and Drug Administration added a black box warning to Xolair, stating that patients must receive injections under direct medical supervision in a health care setting so they can be monitored for signs of anaphylaxis. Anaphylaxis has presented as bronchospasm, hypotension, syncope, urticaria, and angioedema of the throat or tongue in patients receiving as little as one dose of the drug.
Dr. Maurer laid out the patient numbers that make pursuing an indication for omalizumab in urticaria an attractive proposition. The prevalence of urticaria in Europe is estimated at 1.3%, or more than 10 million individuals. Three-quarters of them have chronic spontaneous urticaria and one-quarter have inducible urticaria. The only drugs licensed for the treatment of urticaria are antihistamines, and an estimated 5.7 million Europeans with urticaria are not adequately controlled on those medications.
“Anything else that's second-, third-, or fourth-line is not licensed for treatment of urticaria patients, so we're in desperate need of new therapies for patients who are resistant to nonsedating antihistamines,” he said.
Questions that remain to be answered before omalizumab can earn an indication for urticaria include its efficacy in types other than autoallergic urticaria, the drug's mechanism of action, and optimal dosing.
Anecdotally, Dr. Maurer said that he and his colleagues have successfully treated patients with antihistamine-refractory spontaneous urticaria, cold urticaria, physical urticaria, cholinergic urticaria, solar urticaria, pressure urticaria, and other forms of the disease. “It doesn't seem to matter what type of urticaria you suffer from. The benefit from Xolair is tremendous,” he said.
Audience members were quick to ask about the cost, which is high.
“It's about 500 euro [about $750] per injection, and these patients typically need one or two injections per month,” Dr. Maurer replied. “But remember, these patients suffer tremendously, they miss work, and the other drugs are not cheap either.”
Also in the developmental pipeline are small-molecule IgE inhibitors that are far less expensive to produce than biotech agents and are suitable for oral administration, he noted.
The study was funded by Genentech and Novartis. Dr. Maurer has served as a consultant to the companies.
'For those of you who know urticaria … there's no other drug that can do this.'
Source DR. MAURER