Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen–induced seasonal allergic rhinitis

doi:10.1067/mai.2000.108310

Journal of Allergy and Clinical Immunology

Volume 106, Issue 2, August 2000, Pages 253-259

https://doi.org/10.1067/mai.2000.108310 Get rights and content

Abstract

Background: Allergic rhinitis is a common condition often requiring treatment. Objective: We evaluated whether recombinant humanized (rhu)mAb-E25, a recombinant humanized construct of a murine antibody that binds to circulating IgE, could control symptoms and reduce intake of concomitant medication in seasonal allergic rhinitis (SAR) induced by birch pollen if given subcutaneously in a dose schedule predicted to reduce serum free IgE levels below 25 ng/mL. Methods: We randomly assigned 251 adult subjects with a history of SAR and a positive skin test response to birch pollen to receive 300 mg of rhumAb-E25 or placebo given 2 or 3 times during the season, depending on baseline IgE levels. The primary efficacy variable was the subject's average daily nasal symptom severity score (sneezing, itching, runny, and stuffy nose) from diary data collected over the double-blind treatment period. Secondary efficacy variables included the average number of rescue antihistamine tablets per day, the proportion of days with any SAR medication use, and rhinoconjunctivitis-specific quality of life (QOL). Results: Significant between-treatment differences in favor of rhumAb-E25 were observed in average daily nasal symptom severity scores, the average number of tablets of rescue antihistamines per day, the proportion of days with any SAR medication use, and all domains of QOL. Serum-free IgE levels were markedly lower in rhumAb-E25–treated subjects and were associated with clinical effectiveness. Recombinant humanized mAb-E25 was well tolerated. No anti-rhumAb-E25 antibodies were detected. Conclusion: Compared with placebo, rhumAb-E25 was safe and effective in controlling birch pollen–induced SAR symptoms, with less concomitant medication use and improved QOL. This study shows the therapeutic potential of anti-IgE antibody in SAR. (J Allergy Clin Immunol 2000;106:253-9.)

Section snippets

Study subjects

Subjects were aged 17 to 66 years (53% female subjects), weighed 48 to 110 kg, and had the following: a positive skin prick test response to birch pollen extract (wheal of equal or larger size as that produced with 10 mg/mL histamine and at least 3 mm in diameter; Soluprick subcutaneous 10 HEP, ALK Laboratories, Horsholm, Denmark), a history of at least 4 moderate-to-severe symptoms of SAR toward birch pollen (sneezing, itchy nose, runny nose, stuffy nose, watery eyes, red eyes, itchy eyes, or

Baseline characteristics and accounting of patients

Two hundred fifty of the 251 randomized subjects received study treatment: 164 received rhumAb-E25 (165 randomized), and 86 received placebo. The baseline characteristics of the subjects were similar between treatment groups (Table I).

. Baseline characteristics for all randomized subjects

Characteristic	rhumAb-E25 (n = 165)	Placebo (n = 86)
Age (y)
Mean ± SD	33 ± 10.4	34 ± 10.1
Range	17-66	19-64
Female sex (%)	52	56
Caucasians (%)	99	97
Height (cm)
Mean ± SD	173 ± 9.8	173 ± 8.6
Range	150-200	156-191
Weight (kg)
Mean ± SD

Discussion

This randomized, double-blind, placebo-controlled trial showed that rhumAb-E25, a humanized anti-IgE mAb, was well tolerated and effective in preventing and controlling symptoms of pollen-induced SAR, while reducing the use of rescue and concomitant SAR medication, and had a positive effect on QOL.

Our study covered an 8-week observation period, with all study days included in the analysis, independent of the pollen counts. This time period was considered necessary to maximize the likelihood of

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^☆: Supported by Novartis Pharmaceuticals, Basel, Switzerland, and Genentech Inc, South San Francisco, Calif.

^☆☆: Received for publication •••.

^★: Reprint requests: Ellinor Ädelroth, MD, PhD, Department of Respiratory Medicine and Allergy, University Hospital, S-90185 Umea, Sweden.

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Asthma, rhinitis, other respiratory diseasesRecombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen–induced seasonal allergic rhinitis☆,☆☆,★

Abstract

Section snippets

Study subjects

Baseline characteristics and accounting of patients

Discussion

Variations in the prevalence of respiratory symptoms, self-reported asthma attacks and use of asthma medication in the European Community Respiratory Health Survey (ECRHS)

Eur Respir J

World-wide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis and atopic eczema. ISAAC

Lancet

Epidemiology of rhinitis and asthma

Clin Exp Allergy

Epidemiology of the allergic diseases: are they really on the increase?

Int Arch Allergy Immunol

Evidence for an increase in atopic disease and possible causes

Clin Exp Allergy

The receptor with high affinity for immunoglobulin E

Ann Rev Immunol

Activation of mast cells for mediator release through IgE receptors

Prog Allergy

The pharmacology and use of H1-receptor-antagonist drugs

N Engl J Med

The rationale for the use of topical corticosteroids in allergic rhinitis

Clin Exp Allergy

Topical pharmacotherapy for allergic rhinitis: nedocromil

Am J Otolaryngol

Allergen immunotherapy: therapeutic vaccines for allergic diseases

J Allergy Clin Immunol

Humanization of an antibody directed against IgE

J Immunol

Central role of immunoglobulin (Ig) E in the induction of lung eosinophil infiltration and T helper 2 cell cytokine production: inhibition by a non-anaphylactogenic anti-IgE antibody

J Exp Med

Therapeutic potential of anti IgE antibodies

Curr Opin Immunol

Asthma, rhinitis, other respiratory diseases
Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen–induced seasonal allergic rhinitis☆,☆☆,★