GENEVA – In real-world clinical practice, roughly – and for those who don’t, three-quarters will respond upon updosing to 450 or 600 mg every 4 weeks.
That’s the key message of an open-label study of 286 patients with chronic spontaneous urticaria (CSU) conducted at 15 hospitals by the Catalan and Balearic Chronic Urticaria Network (XUrCB),, reported at the annual congress of the European Academy of Dermatology and Venereology.
In three published, pivotal, phase 3 randomized trials, the clinical response rate to omalizumab at 300 mg every 4 weeks, as defined by a weekly 7-day Urticaria Activity Score (UAS7) of 6 or less at 12 weeks, was 52% in, 66% in , and 52% in . But patients enrolled in formal randomized trials are often quite different from the broader group encountered in daily practice, and the Spanish dermatologists wanted to know if updosing in suboptimal responders was safe and effective. It turns out that it certainly is, according to Dr. Spertino of Teknon Medical Center in Barcelona.
The treatment algorithm followed by the XUrCB investigators was that, if after six doses at the approved dose of 300 mg every 4 weeks a patient didn’t have good control of disease activity, the dose was increased to 450 mg every 4 weeks. If after three doses at that level, there still wasn’t good control of the CSU, the dose was further increased to 600 mg every 4 weeks.
As in the pivotal phase 3 clinical trials, the XUrCB group defined good control of disease activity as a UAS7 score of 6 or less in accord with a study that demonstrated such a score on the 0- to 42-point UAS7 correlates well with minimal or no patient symptoms ().
At baseline, the mean age of the 286 CSU patients was 44.6 years and the mean UAS7 score was 26.5; 74% were women. Forty-seven percent of patients experienced angioedema and 33% had inducible urticaria, most commonly brought forth by pressure or dermographism. One-third of patients had previously been on cyclosporine and half of the patients had a high d-dimer level.
Sixty-five percent of patients achieved good disease control on omalizumab at 300 mg every 4 weeks. Of the 99 patients (35%) who didn’t, 20 patients stopped treatment at their dermatologist’s request because their symptoms remained uncontrolled on the approved dose. But 59 of the 79 who updosed obtained good disease control: 43 on a dose of 450 mg and 16 on a dose of 600 mg.
In multivariate analysis, two predictors of treatment success with updosing were identified: previous treatment with cyclosporine and obesity. Among patients previously on cyclosporine – a marker for more severe disease – only 21% achieved a UAS7 score of 6 or less on the approved dose, while 41% did so upon updosing. And obesity was associated with a 3.7-fold increased likelihood of a favorable response to updosing after lack of treatment success at the approved dose.
Neither a high d-dimer or serum IgE level, baseline UAS7 score, gender, associated angioedema, nor inducible urticaria was significantly associated with an increased treatment success rate upon updosing.
Updosing proved to be safe. All adverse events were mild and infrequent, consisting of headache, local injection site reactions, and arthromyalgia s, each occurring in 1%-2% of patients. Frequencies were similar in updosed patients and those on the approved dosing schedule.
Session cochair Jorgen Serup, MD, DMsc, congratulated Dr. Spertino for supplying physicians with “very-much-needed data.”
“This is very convincing data and highly clinically relevant for those of us who have these patients in our practices,” said Dr. Serup, professor of dermatology at Copenhagen University.
Dr. Spertino reported having no financial conflicts of interest regarding his presentation.
SOURCE: Spertino J et al.