A randomized multicenter study evaluating Xolair persistence of response after long-term therapy.
BACKGROUND
Few data are available to assist clinicians with decisions regarding long-term use of asthma therapies, including omalizumab.


OBJECTIVE
We sought to evaluate the benefit and persistence of response in subjects continuing or withdrawing from long-term omalizumab treatment.


METHODS
Evaluating the Xolair Persistency Of Response After Long-Term Therapy (XPORT) was a randomized, double-blind, placebo-controlled withdrawal study that included subjects with moderate-to-severe persistent asthma receiving long-term omalizumab. Subjects were randomized by using a hierarchical dynamic randomization scheme to continue their same dose of omalizumab or withdraw to placebo and were then followed every 4 weeks for 1 year. The primary outcome was any protocol-defined severe asthma exacerbation. The secondary outcome was time to first protocol-defined severe asthma exacerbation. Exploratory outcomes included changes in Asthma Control Questionnaire and Asthma Control Test scores.


RESULTS
Significantly more subjects in the omalizumab group (67%) had no protocol-defined exacerbation than in the placebo group (47.7%); an absolute difference of 19.3% (95% CI, 5.0%, 33.6%) represents a 40.1% relative difference. Time to first protocol-defined exacerbation analysis revealed a significantly different between-group exacerbation pattern that was consistent with the primary analysis. Subjects continuing omalizumab had significantly better asthma control (mean [SD] change from baseline to week 52: Asthma Control Test score, -1.16 [4.14] vs placebo, -2.88 [5.38], P = .0188; Asthma Control Questionnaire score, 0.22 [0.66] vs placebo, 0.63 [1.13], P = .0039). Discontinuation of omalizumab was associated with an increase in free IgE levels and an increase in basophil expression of the high-affinity IgE receptor. No safety concerns were noted.


CONCLUSIONS
Continuation of omalizumab after long-term treatment results in continued benefit, as evidenced by improved symptom control and reduced exacerbation risk.
Morsani College of Medicine and James A. Haley VA Hospital, University of South Florida, Tampa, Fla. Electronic address: dledford@health.usf.edu.
Dennis
D
Ledford
University of Wisconsin, Madison, Wis.
William
W
Busse
Genentech, Inc, South San Francisco, Calif.
Benjamin
B
Trzaskoma
Genentech, Inc, South San Francisco, Calif.
Theodore A
TA
Omachi
Genentech, Inc, South San Francisco, Calif.
Karin
K
Rosén
Capital Allergy & Respiratory Disease Center, Sacramento, Calif.
Bradley E
BE
Chipps
Dean Clinic, Madison, Wis.
Allan T
AT
Luskin
Genentech, Inc, South San Francisco, Calif.
Paul G
PG
Solari
D000293:Adolescent; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004311:Double-Blind Method; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D000069444:Omalizumab / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
D018927:Anti-Asthmatic Agents; D000069444:Omalizumab; D009569:Nitric Oxide; D007073:Immunoglobulin E
Asthma; IgE; eosinophilia; exacerbations; fractional exhaled nitric oxide; high-affinity IgE receptor; long-term treatment; omalizumab; persistence