To examine the evidence derived from randomized controlled clinical trials on the efficacy and safety of omalizumab compared to placebo in controlling symptoms of chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU).
The electronic databases PubMed, Medline, EMBASE, Biomed Central, The Cochrane Central Register of Controlled Trials (CENTRAL), Wiley, OVID, and HighwirePress were reviewed. The date limit was set to May 31th, but it was extended to September 30th of 2014 due to a new publication. No language restriction was used. The articles included were randomized trials controlled with placebo in individuals older than 12 years diagnosed with CIU/CSU refractory to conventional treatment, the intervention being, omalizumab at different doses, and the comparison, placebo. The primary outcome was symptom improvement according to the weekly score of urticaria severity (UAS7), the itch severity score (ISS), the weekly score of number of urticarial lesions, the dermatology life quality index, and the chronic urticaria quality of life questionnaire (CU-QoL). Databases were searched using the following Mesh or EMTREE key words including as intervention “omalizumab” or “humanized monoclonal antibody,” compared to placebo and the disease of interest “urticaria” or “angioedema”. The title, abstract and article were reviewed by two independent investigators, according to the selection criteria in each of the databases. An assessment of the quality of the articles was performed according to the bias tool from the studies of the Cochrane Collaboration. Information such as author data, date of study, number of participants, interventions, dose and frequency of administration, comparison, time of follow-up, measurements of weekly score of urticaria activity, pruritus severity score, weekly urticarial lesions, percentage of angioedema and post-treatment change were extracted. Frequency of adverse events and the ones suspected to be caused by the intervention drug were included.
770 records were identified in all databases described. 720 were eliminated for failing to meet the inclusion criteria in the first review or for duplicate records. 24 articles were reviewed by abstract, 18 additional articles were further removed, leaving 6 records for inclusion. An experimental study was excluded because it wasn’t randomized. Five studies were finally included, with 1117 patients, of these 831 received a dose of omalizumab of 75 mg (183 patients, 16.38%), 150 mg (163 patients, 14.59%), 300 mg (437 patients, 39.12%) or 600 mg (21 patients, 1.8%), as a single dose, or every 4 weeks until 24 weeks maximum. The average age was 42.07 years, predominantly female gender and white ethnicity. It was observed that the use of omalizumab 300 mg lowered the weekly scores of urticarial activity in 19.9 vs. 6.9 on placebo (p <0.01), 19 vs 8.5 and 20.7 vs 8.01 in three studies, the weekly ISS (−9.2 vs. - 3.5, p <0.001, −9.8 vs −5.1 p < 0.01, −8.6 vs −4.0 and −9.4 vs −3.63 p <0.001 in four studies), and the percentage of angioedema-free days (omalizumab 95.5% vs. placebo 89.2% p <0.001, and 91.95% vs. 88.1% p <0.001 in two of the studies respectively).
The different doses used throughout the study, time of administration and follow-up periods ranged from single dose to monthly dose for 24 weeks. Therefore no meta-analysis of the review was conducted.
Conclusions and implications of the main findings
Despite the limitations, it is considered that omalizumab 300 mg is effective in treating chronic idiopathic urticaria refractory to H1 antihistamines. Further studies are required to determine the duration of effective treatment.
Registration number of the systematic review
CRD42014010029 (PROSPERO. International Prospective Register of Systematic Reviews).