GENEVA – Omalizumab for treatment of chronic spontaneous urticaria brings about a profound improvement in angioedema-related quality of life, a widely underappreciated dimension of the impairment caused by this disease, Karsten Weller, MD, said at the annual congress of the European Academy of Dermatology and Venereology.
Bruce Jancin/Frontline Medical News
Dr. Karsten Weller
He presented key findings of the X-ACT study, a phase 3 double-blind, placebo-controlled, randomized trial of omalizumab (Xolair) for chronic spontaneous urticaria (CSU) that focused specifically on the monoclonal antibody’s effect on angioedema-related quality of life. Such a study, he added, is long overdue.
“Virtually all clinical studies of CSU in recent decades focus on the wheal and pruritus components and not on the angioedema component, even though angioedema is a frequent symptom in the disease. Roughly half of patients with CSU experience wheals and angioedema, and up to 13% experience angioedema only,” said Dr. Weller, a dermatologist at Charité University Hospital in Berlin.
“Angioedema is a major driver of quality-of-life impairment in CSU,” he continued. “We know that these are the patients who particularly suffer from the unpredictability of the disease, from disfigurement, from embarrassment. These are the patients who come to the emergency rooms, who lose working days, and these are the patients who often have the feeling of losing control over their lives.”
X-ACT was a multicenter German study which included 91 patients with moderate to severe CSU marked by at least four angioedema episodes during the 6 months prior to enrollment. Participants also had to be refractory to second-generation H1 antihistamines at two to four times the approved dose. The subjects were randomized to subcutaneous omalizumab at 300 mg every 4 weeks or placebo for 28 weeks; they were then further assessed for changes in quality of life during 8 weeks off omalizumab.
Because assessment of quality of life was such a major part of X-ACT, the investigators pulled out all the stops. Their multimodal evaluation included the Angioedema Quality of Life questionnaire – a patient-reported, 17-item instrument that is the first validated tool for evaluation of angioedema-specific quality of life – as well as the Dermatology Life Quality Index and the weekly Angioedema Activity Score.
Patients were also asked to rate on a 0-4 scale their degree of fearfulness of life-threatening swelling episodes and also their degree of fearfulness of angioedema-related suffocation. “To my knowledge, this is the first time this has been done in a randomized clinical trial,” Dr. Weller noted.
The patient reports were striking: At baseline, 49% indicated that they occasionally, often, or very often were afraid of suffocating caused by swelling episodes; only 4% of patients expressed that fear after 28 weeks on omalizumab, compared with 25% of placebo-treated controls. Similarly, at baseline two-thirds of patients reported occasionally, often, or very often being fearful of life-threatening swelling episodes, a rate that fell to 14% after 28 weeks on omalizumab, compared with 42% for controls.
Scores on the Angioedema Quality of Life Questionnaire improved continuously from a baseline of roughly 60 on a 0-100 scale – indicative of severe impairment – to less than 20 after 28 weeks on omalizumab; these scores steadily worsened again during the 8 weeks following treatment discontinuation. The Dermatology Life Quality Index scores dropped from a mean baseline of 15.6 down to 5 by week 4, remained in the 3-5 range for the remainder of the treatment period, then increased again when treatment was discontinued. The Angioedema Activity Score followed a similar pattern.
One audience member observed that the placebo response was quite strong in the study, with the percentage of patients reporting fear of suffocating caused by angioedema episodes falling from 49% at baseline to 25% after 28 weeks on placebo.
Dr. Weller replied that a potent placebo response is a consistent feature of all clinical trials of CSU therapies. The explanation, he added, is unknown.
He reported receiving research grants from and serving as a consultant to Novartis, which sponsored the X-ACT trial.