Casale TB, Condemi J, LaForce C, et al. JAMA. 2001;286:2956–2967
Purpose of the Study.
Seasonal allergic rhinitis is a common immunoglobulin E (IgE)-mediated disorder that produces troublesome symptoms. A recombinant humanized monoclonal anti-IgE antibody (omalizumab) forms complexes with free IgE, blocking its interaction with mast cells and basophils and lowering free IgE levels in the circulation. This study specifically seeks to assess the efficacy and safety of omalizumab for prophylaxis of symptoms in patients with seasonal allergic rhinitis.
Patients 12 to 75 years old with no or mild symptoms during the preceding month but with at least a 2-year history of moderate-to-severe seasonal allergic rhinitis attributable to ragweed were considered eligible for the study. The history of moderate to severe ragweed-induced allergic rhinitis was defined as having a score of 2 or more on a 0- to 3-point scale (0 = no symptoms; 3 = severe symptoms), in 4 of 8 symptom categories (sneezing, itchy nose, runny nose, stuffy nose, watery eyes, red eyes, itchy eyes, or itchy throat) based on patient recall of the previous ragweed pollen season. Skin test sensitivity to ragweed pollen and a baseline total IgE level of between 30 and 700 IU/mL also were required.
This randomized, double-blind, dose-ranging, placebo-controlled trial assigned patients to receive omalizumab, 50 mg (n = 137), 150 mg (n = 134), or 300 mg (n = 129), or placebo (n = 136) subcutaneously just before ragweed season and repeated during the pollen season every 3 weeks in patients with baseline IgE levels of 151 to 700 IU/mL (4 total treatments) and every 4 weeks in patients with baseline IgE levels of 30 to 150 IU/mL (3 total treatments). Main outcome measures were self-assessed daily nasal symptom severity scores (range: 0–3), rescue antihistamine use, and rhinitis-specific quality of life during the 12 weeks from the start of the treatment.
Nasal symptom severity scores were significantly lower in patients who received 300 mg omalizumab than in those who received placebo (P = .002). A significant association was observed between IgE reduction and nasal symptoms and rescue antihistamine use. A linear dose-response relationship was observed for average daily nasal symptom scores and omalizumab dose. Patients in the 300-mg and the 150-mg omalizumab groups had significantly greater percentage of days with minimal nasal symptoms versus those in the placebo group. Rhinitis-specific quality of life scores were consistently better in patients who received 300 mg of omalizumab than in those who received lower dosages or placebo and did not decline during the peak season. A dose-dependent decrease in serum-free IgE levels occurred after omalizumab treatment. The frequency of adverse events was not significantly different among the omalizumab and placebo groups.
Omalizumab decreased serum-free IgE levels and provided clinical benefit in a dose-dependent fashion in patients with seasonal allergic rhinitis. This was demonstrated by decreased average daily nasal symptom scores, daily nasal and ocular symptom severity and duration scores, and assessment of quality of life scores. Patients receiving 300 mg omalizumab also experienced profound reductions in serum-free IgE levels after the first dosing interval, when 63% of patients had serum-free IgE levels <10.4 IU/mL.
This well-designed study thoroughly assesses the impact that omalizumab can have on the treatment of allergic rhinitis. There are, however, several limitations to this study. According to the article, only two thirds of patients were exposed to the severe pollen season. Therefore, variability in ragweed exposure across different sites in the United States is one factor that must be considered. It should also be known that patients entering the study were not completely asymptomatic, which could be attributable to a lingering effect from allergic rhinitis symptoms from the spring allergy season. However, this 12-week study of patients with seasonal allergic rhinitis did demonstrate that omalizumab therapy decreased serum-free IgE levels and provided clinical benefits, improving rhinitis-specific quality of life and reducing rescue medication use. Additional studies are necessary to pinpoint the exact placement of this agent in the therapeutic regimen for treatment of seasonal allergic rhinitis.