A review of omalizumab for the management of severe asthma

Figures & data

Table 1 Patient characteristics and primary endpoints of trials included

Source	Study design			Baseline characteristicsa				Efficacy
	Study design	Number of patients	Treatment duration (wk)	Age (yr)	FEV1 (%pred)	Serum IgE level (IU/mL)	Baseline ICS use (μg/d)	Primary end points
MacGlashan et al^Citation23  Omalizumab	OL	15	n/a	29.8	n/a	192	n/a	Free IgE levels: decrease to 1% of pretreatment levels. FcεRI densities: 97% reduction.
Humbert et al^Citation28  Omalizumab  Control	DB	419	28	43.4 43.3	61.0 61.6	197.6 189.6	2,359b 2,301b	Clinically significant asthma exacerbation rate: 0.68 vs 0.91 with placebo (RR =0.738, P=0.042).
Lanier et al^Citation35  Omalizumab  Control	DB	627	52	8.7 8.4	86.0 87.2	476.0 456.9	517.8c 509.5c	Clinically significant asthma exacerbations: 31% (24 wk), 43% (52 wk) reductions. ICS dose (adjustable steroid phase): 4% reduction vs 2% increase in placebo. Safety: no difference in overall incidence of AE.
Milgrom et al^Citation36  Omalizumab  Control	DB	334	28	9.4 9.5	84 85	348 323	284b 267b	Steroid-reduction phase:  1. % patient with complete BDP withdrawal: 55% vs 39% with placebo.  2. % patients had asthma exacerbation episodes: 18.2% vs 38.5% with placebo. Safety: no evidence of clinically significant drug toxicity or serious treatment-related AEs.

Notes:

a Data are shown as mean;

b BDP equivalent;

c fluticasone propionate equivalent.

Abbreviations: BDP, beclomethasone dipropionate; FEV₁, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; IgE, immunoglobulin E; OL, open-label; DB, double-blind; AEs, adverse events; wk, weeks; yr, year; n/a, not applicable; RR, risk ratio.

Table 2 Patient characteristics and clinical outcomes of real-life studies included

Source	Study design		Baseline characteristicsa				Effectiveness
	Number of patients	Treatment duration	Age (yr)	FEV1 (%pred)	Serum IgE level (IU/mL)	Baseline ICS use (μg/d)	Clinical outcomes
Molimard et al^Citation30	147	n/a	46.5	n/a	283.4	3,071.2b	Patients with 5 mo of follow-up or longer:  Annual rate of exacerbations requiring OCS: 62% reduction.  Use of OCS: 48.1% reduction or discontinuation.  Annual rate of emergency visits: 65% reduction.  Annual rate of hospitalizations: 29% reduction.
Brusselle et al^Citation31	158	52 wk	48.2	56.5	613.9	n/a	Treatment effectiveness (in ITT):  % patient improving in 2005 GINA classification: 31%.  Magnitude of FEV1 improvement: 12.23%.a  % patient improving in AQLQ total score >0.5: 84.4%.  % PERSIST severe exacerbationc free: 65.6%.  Number of health care visits: reduction of 1.49 visits.a
Barnes et al^Citation32	136	n/a	41.3	62.9	n/a	n/a	Daily OCS dose: 25.6% reduction.  Number of asthma exacerbation: 1.7 events/yr vs 3.67 events/yr at baseline.a  Amount of FEV1 improvement: 12.8%.a
Cazzola et al^Citation33	142	1 yr	49.6	64.8	297.4	2,224.7	Annual exacerbation rate: 78% reduction.  Annual emergency visits rate: 87% reduction.  Annual hospitalization rate: 96% reduction.  ICS dose (patients with over 12 mo of treatment): 1,604.6 μg/d.a
Braunstahl et al^Citation34	943	2 yr	45	n/a	323.1	n/a	Proportion of patients with no clinically significant exacerbations: 54.1% (12 mo) and 67.3% (24 mo) vs 6.8% at baseline.  Proportion of patients taking OCS (in ITT): 16.1% (12 mo) and 14.2% (24 mo) vs 28.6% at baseline.  Total daily OCS dose: 7.7 mg (12 mo) and 5.8 mg (24 mo) vs 15.5 mg at baseline.a
Deschildre et al^Citation38	104	52 wk	11.9	88	1,125	703d	Asthma control:  % children achieving good control level (based on GINA criteria): 67% vs 0% at baseline.  Exacerbation rate: 72% reduction.  Health care utilization: 88.5% reduction in hospital admissions.  ICS dose: reduction of 212 μg,a,d equivalent to a 30% reduction.
Odajima et al^Citation39	38	24 wk	10.7	90.3	335.5	469.7	Asthma control:  Geometric mean of serum free IgE levels:  15.6 ng/mL (vs 778.7 ng/mL at baseline).a  Asthma exacerbation rate: 69.2% reduction.  Hospitalization rate: 78.2% reduction.  % patients reduced controller medication: 28.9%.

Notes:

a Data are shown as mean;

b equivalent BDP;

c PERSIST severe exacerbations were those that met the following criteria: the patient required a systemic corticosteroid, or the patient required an emergency room visit or hospitalization for the exacerbation;

d fluticasone propionate equivalent.

Abbreviations: AQLQ, asthma quality of life questionnaire; BDP, beclomethasone dipropionate; FEV₁, forced expiratory volume in 1 second; GINA, Global Initiative for Asthma; ICS, inhaled corticosteroid; IgE, immunoglobulin E; ITT, intent to treat; OCS, oral corticosteroids; n/a, not applicable; wk, weeks; yr, years; mo, months.

MacGlashanDWJrBochnerBSAdelmanDCDown-regulation of Fc(ε)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibodyJ Immunol19971583143814459013989

 PubMed Web of Science ®Google Scholar

HumbertMBeasleyRAyresJBenefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATEAllergy200560330931615679715

 PubMed Web of Science ®Google Scholar

LanierBBridgesTKulusMTaylorAFBerhaneIVidaurreCFOmalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthmaJ Allergy Clin Immunol200912461210121619910033

 PubMed Web of Science ®Google Scholar

MilgromHBergerWNayakATreatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab)Pediatrics20011082E3611483846

 PubMed Web of Science ®Google Scholar

MolimardMde BlayFDidierALe GrosVEffectiveness of omalizumab (Xolair) in the first patients treated in real-life practice in FranceRespir Med20081021717617920257

 PubMed Web of Science ®Google Scholar

BrusselleGMichilsALouisR“Real-life” effectiveness of omalizumab in patients with severe persistent allergic asthma: the PERSIST studyRespir Med2009103111633164219619998

 PubMed Web of Science ®Google Scholar

BarnesNMenzies-GowAMansurAHEffectiveness of omalizumab in severe allergic asthma: a retrospective UK real-world studyJ Asthma201350552953623574000

 PubMed Web of Science ®Google Scholar

CazzolaMCamiciottoliGBonaviaMItalian real-life experience of omalizumabRespir Med2010104101410141620483574

 PubMed Web of Science ®Google Scholar

BraunstahlGJChenCWMaykutRGeorgiouPPeacheyGBruceJThe eXpeRience registry: the ‘real-world’ effectiveness of omalizumab in allergic asthmaRespir Med201310781141115123721684

 PubMed Web of Science ®Google Scholar

DeschildreAMarguetCSalleronJAdd-on omalizumab in children with severe allergic asthma: a 1-year real life surveyEur Respir J20134251224123323520319

 PubMed Web of Science ®Google Scholar

OdajimaHEbisawaMNagakuraTOmalizumab in Japanese children with severe allergic asthma uncontrolled with standard therapyAllergol Int201564436437026433533

 PubMed Web of Science ®Google Scholar