DermatologistsBlog.com Interview with Prof Dr. Ana GImenez-Arnau
Department of Dermatology.
Hospital del Mar. IMIM. Universitat Autònoma Barcelona
DermatologistsBlog.com: What are the main findings of the study?
Dr. Gimenez-Arnau: The main issue of this study was to demonstrate the efficacy of omalizumab obtaining relief of the urticaria symptoms (itch and hives) of moderate to severe chronic spontaneous urticaria in patients who are refractory to the actual approved treatments, non-sedative antihistamines at licensed doses. The term chronic just refers to the disease definition, this means long-lasting more than 6 weeks, but does not mean the urticaria is for all the life.
This study is designed to define the minimal effective dose. Because of this, three doses were compared with placebo, 75 mg, 150 mg and 300 mg. The primary efficacy outcome was the change from baseline in a weekly itch-severity score. Different secondary end points were also analyzed among others changes from baseline in the Urticaria Activity Score 7(assess wheals +itch), from the score for the weekly number of hives or the Dermatology Quality of Life Index.
And what the results show, is that at minimum dose of 150 mg subcutaneously administered monthly, showed significant differences compared with placebo for all the endpoints analyzed except for angioedema control.
300 mg of omalizumab administered monthly showed significant benefit compared with placebo also, with a higher rate of complete response for hives (44%) compared with 150 mg (22%) being also significantly effective controlling also angioedema.
The active treatment was administered just three months and during the follow up the disease slowly reappeared in most of the patients, as it was expected. You should know, the patients included in the study suffered of this skin condition a mean of 6.5 years. And because its refractory behavior with antihistamines H1 these patients would use immunosuppressive drugs as corticosteroids or cyclosporine, effective but less safe drugs.
DermatologistsBlog.com: Were any of the findings unexpected?
Dr. Gimenez-Arnau: The efficacy results observed where as we expected, because previous isolated reports, open label studies, and some phase II studies developed showed omalizumab as a potential effective drug to control this extremely disturbing condition. People who suffer of Chronic Spontaneous Urticaria show an impairment of their quality of life comparable with cardiovascular patients. What this study shows for the first time is what we exactly could expect of the drug at the doses employed helping to establish the minimal effective drug.
Now the work starts, based in the results of this trial and the results of two more trials already finished and which results will be published in a near future will help to define a recommended dose to start with an effective treatment.
DermatologistsBlog.com: What should clinicians and patients take away from this study?
Dr. Gimenez-Arnau: We should point your attention about how the effectiveness of omalizumab was assessed in this trial. The primary and secondary endpoints were assessed always by the patient, without any intervention by the physician or the nurses. All the parameters were assessed daily by the patients two times per day and send to a central pool. The follow up of each patient was at real time. The compliance of the patients with the treatment and the assessment was excellent. This fact submitted omalizumab to the more strict and real judge, the patient.
DermatologistsBlog.com: How will omalizumab will be used?
Dr. Gmenez-Arnau: Omalizumab will be used completely differently than it is used today for severe asthma. Habitually these chronic urticaria patients show a mean IgE level of 168.2, just slightly elevated. The dose will be chosen not based in the IgE level as it occurs in asthma. According to an expert consensus held last November 2012 in Berlin, omalizumab will be recommended when high doses of non-sedative H1 antihistamines fail to control chronic spontaneous urticaria.
Omalizumab was included as third line treatment as cyclosporine A was. This meeting is the basis of the International Guidelines on Management of Urticaria supported by most of the Dermatological and Allergy Scientific Societies that will be published during this 2013. These guidelines are the update of the already published in 2009. Omalizumab is a safer drug than cyclosporine.
DermatologistsBlog.com: What recommendations do you have for future research as a result of your study?
Dr. Gimenez-Arnau: This study and the results from the other two phase III trials are a very good demonstrations of efficacy and should be the basis to obtain the authorization to be used in chronic urticaria patients. Our patients need this registration. Itch is probably as disturbing as severe pain. Recurrent daily hives appearing endogenously, not environmental induced, that people can’t avoid because in most of the cases shows autoimmune basis long-lasting months and years just can be understand by the patient itself. Nowadays we can’t stop our life, our work our social life because of urticaria as it was in the XIX century. For the future we need to develop studies that will help to the physician to use the drug, ideal dose, how long, how to reduce the dose, control potential adverse events, do a good pharmacosurveillance through a good register. Chronic urticaria is not a permanent disease for all the life, the correct treatment should help to control early the disease avoiding health expenses.
Omalizumab for the Treatment of Chronic Idiopathic or Spontaneous Urticaria
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; 368:924-935
March 7, 2013DOI: 10.1056/NEJMoa1215372