A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy Robert A.

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Presentation transcript:

A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy Robert A. Wood, MD, Jennifer S. Kim, MD, Robert Lindblad, MD, Kari Nadeau, MD, PhD, Alice K. Henning, MS, Peter Dawson, PhD, Marshall Plaut, MD, Hugh A. Sampson, MD Journal of Allergy and Clinical Immunology Volume 137, Issue 4, Pages 1103-1110.e11 (April 2016) DOI: 10.1016/j.jaci.2015.10.005 Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 CONSORT diagram. On the first day, dosing was initiated with 0.07 mg of milk protein. Subjects were required to tolerate dose 6 (2.1 mg) at dosing visit 1 and dose 8 (9 mg) by visit 2. Daily home dosing was continued, and subjects returned every 2 weeks for dose escalation for a minimum of 22 and a maximum of 40 weeks. Subjects were required to reach a minimum maintenance dose of 520 mg of milk protein (equivalent to 15 mL of liquid milk). Journal of Allergy and Clinical Immunology 2016 137, 1103-1110.e11DOI: (10.1016/j.jaci.2015.10.005) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 A and B, Casein- and β-lactoglobulin–specific IgG4 levels were measured at baseline and months 4, 16, 22, 28, 30, and 32. Median values are represented by blue stars. Significant increases from baseline were detected within both treatment groups from month 16 onward (all P < .0001), with no differences seen between the 2 groups. C and D, The ratio of casein and β-lactoglobulin IgG4/IgE was calculated after IgG4 levels were converted from milligrams of allergen per liter to nanograms per milliliter and IgE levels were converted from kilounits of allergen per liter to nanograms per milliliter with the folowing formula (IgG4 × 1000) ÷ (IgE × 2.4). Significant increases from baseline were detected within both treatment groups from month 16 onward (all P < .0001). The only significant difference between treatment groups was observed at month 4, with omalizumab-treated subjects exhibiting decreased casein and β-lactoglobulin IgG4/IgE ratios compared with placebo-treated subjects. BL, Baseline; M, month. Journal of Allergy and Clinical Immunology 2016 137, 1103-1110.e11DOI: (10.1016/j.jaci.2015.10.005) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 A-C, Milk-, casein-, and β-lactoglobulin–specific IgE levels were measured at baseline and months 4, 16, 22, 28, 30, and 32. Median values are represented by blue stars. In the placebo group, after a nonsignificant increase in milk-specific IgE levels at month 4, milk- and casein-specific IgE levels were significantly reduced at all subsequent time points, and β-lactoglobulin–specific IgE levels did not significantly change. In the omalizumab group milk- and casein-specific IgE levels were significantly increased at month 4 and reduced at month 32, and β-lactoglobulin–specific IgE levels were significantly increased at months 4 and 16 compared with baseline values. Comparing the treatment groups, there were significant differences in the change from baseline for milk-specific IgE levels through month 30, for casein-specific IgE levels through month 28, and for β-lactoglobulin–specific IgE levels through month 22. D and E, Casein- and β-lactoglobulin–specific IgG levels were measured at baseline and months 4, 16, 22, 28, 30, and 32. Median values are represented by blue stars. Significant increases from baseline were detected within both treatment groups from month 16 onward (all P < .0001), with no differences seen between the 2 groups. BL, Baseline; M, month. Journal of Allergy and Clinical Immunology 2016 137, 1103-1110.e11DOI: (10.1016/j.jaci.2015.10.005) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Milk end point SPT titration. SPT end point titrations were conducted at baseline and months 28 and 32. Both groups exhibited a significant change from baseline (P < .0001 at months 28 and 32), but there was no difference between the groups in change from baseline at any of the 3 time points. BL, Baseline; M, month. Journal of Allergy and Clinical Immunology 2016 137, 1103-1110.e11DOI: (10.1016/j.jaci.2015.10.005) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Basophil activation by treatment group. Basophil activation was assessed at baseline and months 4, 16, 22, 28, 30, and 32. A repeated-measures analysis of percentage CD63+ cells over time through month 32 found a decrease in the omalizumab group compared with the placebo group through month 28, after which values for omalizumab increased until they were similar to those for placebo at month 32 such that the interaction between treatment and visit was statistically significant (interaction term for 10 μg/mL milk: P < .0001; interaction term for 1 μg/mL milk: P = .009). At the 0.1 μg/mL milk stimulant level, similar trends were seen, but the interaction term was not significant; the P value for the treatment effect was significant (P = .003). At the 0.01 and 0.001 μg/mL milk stimulant levels, no statistically significant differences were seen. BL, Baseline; M, month. Journal of Allergy and Clinical Immunology 2016 137, 1103-1110.e11DOI: (10.1016/j.jaci.2015.10.005) Copyright © 2015 American Academy of Allergy, Asthma & Immunology Terms and Conditions