Seasonal variations of serum-IgE and potential impact on dose-calculation of omalizumab (rhuMab-E25, anti-IgE)

Abstract

The anti-IgE antibody Omalizumab has been approved for the treatment of perennial allergic asthma. Dosing of omalizumab is adjusted according to total IgE levels and body weight, and a near complete suppression of free IgE is deemed to be necessary for optimal efficacy. Many asthmatics, however, have additional sensitisations against seasonal allergens, e. g. pollen, and seasonal exposure may increase total and specific IgE levels ("boost"), thus leading to an imbalance between IgE levels and omalizumab with possible impact on therapeutic outcome. We studied serum total and specific (timothy grass) IgE levels in 17 patients with seasonal allergic rhinitis and/or asthma prior to and during the grass pollen season. Based on total IgE levels, we then calculated hypothetical doses of omalizumab required for treatment at each time point. During the pollen season, total IgE increased significantly from a pre-seasonal mean of 89 (50 - 178) kU/l (geom. mean with 95 % confidence interval) to 126 (63 - 251) kU/l (p = 0.0006). Accordingly, specific IgE increased from 11 (6.3 - 19) kU/l to 15.1 (8.3 - 29) kU/l (p = 0.0013). Calculated doses of omalizumab based on pre-seasonal IgE levels were: no dosing (IgE < 30 kU/l): n = 2; 150 mg 4-weekly: n = 7; 300 mg 4-weekly: n = 2; 225 mg 2-weekly: n = 4; 300 mg 2-weekly: n = 1; 375 mg 2-weekly: n = 1. Based on seasonal IgE levels, doses of omalizumab would have changed in 5/17 patients requiring the next possible dosing step. Of these, two patients would have fallen out of the current dosing scheme. A seasonal increase of serum total and specific IgE can be observed in patients with pollen allergy, although this increase would have no impact on omalizumab doses in the majority of patient. Individual variations, however, can be large and necessitate a dose correction. Therefore, therapeutic monitoring of free IgE levels during anti-IgE treatment appears as desirable tool.