BACKGROUND:Omalizumab is a monoclonal anti-IgE antibody that is effective for the treatment of allergic respiratory disorders; however, its onset of action is unknown. OBJECTIVE: This study was designed to determine the onset of action of omalizumab through the use of a challenge model to determine time-dependent inhibition of ragweed-induced changes in nasal volume as well as correlate the kinetics of omalizumab-induced decreases in serum free IgE and FcepsilonRI receptors on basophils. METHODS: We conducted a 6-week, randomized, double-blind, placebo-controlled study of 24 rhinitic patients with ragweed allergy. After PD(30) ragweed nasal allergen challenge, patients received either omalizumab, approximately 0.016 mg/kg per IgE (IU/mL), or placebo at days 0 and 28 and were rechallenged with ragweed PD(30) dose biweekly. FcepsilonRI expression on blood basophils was determined by flow cytometry at baseline and 7, 14, 28, and 42 days after treatment. IgE levels were measured at baseline and on days 3, 28, and 42. RESULTS:Mean IgE levels decreased by 96% (P <.001) from baseline within 3 days in the omalizumab group. Baseline 30% ragweed-induced nasal volume response was decreased to 20.4% at 7 to 14 days (P <.001) and 12.2% at 35 to 42 days (P <.001) for the omalizumab group. There was a median decrease in basophil FcepsilonRI expression of 73% (P <.001) in the omalizumab group, with maximum inhibition occurring within 14 days of treatment. No significant changes in IgE levels, nasal allergen challenge responses, or basophil FcepsilonRI expression were observed throughout the study in the placebo group. CONCLUSIONS: Our study showed that the onset of action by omalizumab in blunting ragweed-induced nasal responses is within 2 weeks, and this response was associated with 2 putative mechanisms of action: decreased serum free IgE and decreased FcepsilonRI receptor expression on immune effector cells.
RCT Entities:
BACKGROUND:Omalizumab is a monoclonal anti-IgE antibody that is effective for the treatment of allergic respiratory disorders; however, its onset of action is unknown. OBJECTIVE: This study was designed to determine the onset of action of omalizumab through the use of a challenge model to determine time-dependent inhibition of ragweed-induced changes in nasal volume as well as correlate the kinetics of omalizumab-induced decreases in serum free IgE and FcepsilonRI receptors on basophils. METHODS: We conducted a 6-week, randomized, double-blind, placebo-controlled study of 24 rhinitic patients with ragweedallergy. After PD(30) ragweed nasal allergen challenge, patients received either omalizumab, approximately 0.016 mg/kg per IgE (IU/mL), or placebo at days 0 and 28 and were rechallenged with ragweedPD(30) dose biweekly. FcepsilonRI expression on blood basophils was determined by flow cytometry at baseline and 7, 14, 28, and 42 days after treatment. IgE levels were measured at baseline and on days 3, 28, and 42. RESULTS: Mean IgE levels decreased by 96% (P <.001) from baseline within 3 days in the omalizumab group. Baseline 30% ragweed-induced nasal volume response was decreased to 20.4% at 7 to 14 days (P <.001) and 12.2% at 35 to 42 days (P <.001) for the omalizumab group. There was a median decrease in basophil FcepsilonRI expression of 73% (P <.001) in the omalizumab group, with maximum inhibition occurring within 14 days of treatment. No significant changes in IgE levels, nasal allergen challenge responses, or basophil FcepsilonRI expression were observed throughout the study in the placebo group. CONCLUSIONS: Our study showed that the onset of action by omalizumab in blunting ragweed-induced nasal responses is within 2 weeks, and this response was associated with 2 putative mechanisms of action: decreased serum free IgE and decreased FcepsilonRI receptor expression on immune effector cells.
Authors: Hans D Brightbill; Surinder Jeet; Zhonghua Lin; Donghong Yan; Meijuan Zhou; Martha Tan; Allen Nguyen; Sherry Yeh; Donnie Delarosa; Steven R Leong; Terence Wong; Yvonne Chen; Mark Ultsch; Elizabeth Luis; Sree Ranjani Ramani; Janet Jackman; Lino Gonzalez; Mark S Dennis; Anan Chuntharapai; Laura DeForge; Y Gloria Meng; Min Xu; Charles Eigenbrot; Wyne P Lee; Canio J Refino; Mercedesz Balazs; Lawren C Wu Journal: J Clin Invest Date: 2010-05-10 Impact factor: 14.808
Authors: John A Eckman; Patricia M Sterba; Denise Kelly; Val Alexander; Mark C Liu; Bruce S Bochner; Donald W Macglashan; Sarbjit S Saini Journal: J Allergy Clin Immunol Date: 2009-12-04 Impact factor: 10.793