Mary S. Bradley

Efficacy and Safety of Omalizumab in Patients with Chronic Idiopathic/Spontaneous Urticaria Who Remain Symptomatic on H1 Antihistamines: A Randomized, Placebo-Controlled Study

ASTERIA I was a 40-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous omalizumab as add-on therapy for 24 weeks in patients with chronic idiopathic urticaria/spontaneous urticaria (CIU/CSU) who remained symptomatic despite H1 antihistamine treatment at licensed doses. Patients aged 12–75 years with CIU/CSU who remained symptomatic despite treatment with approved doses of H1 antihistamines were randomized (1:1:1:1) in a double-blind manner to subcutaneous omalizumab 75 mg, 150 mg, or 300 mg or placebo every 4 weeks for 24 weeks followed by 16 weeks of follow-up. The primary end point was change from baseline in weekly itch severity score (ISS) at week 12. Among randomized patients (N=319: placebo n=80, omalizumab 75 mg n=78, 150 mg n=80, 300 mg n=81), 262 (82.1%) completed the study. Compared with placebo (n=80), mean weekly ISS was reduced from baseline to week 12 by an additional 2.96 points (95% confidence interval (CI): −4.71 to −1.21; P=0.0010), 2.95 points (95% CI: −4.72 to −1.18; P=0.0012), and 5.80 points (95% CI: −7.49 to −4.10; P<0.0001) in the omalizumab 75-mg (n=77), 150-mg (n=80), and 300-mg groups (n=81), respectively. The omalizumab 300-mg group met all nine secondary end points, including a significant decrease in the duration of time to reach minimally important difference response (⩾5-point decrease) in weekly ISS (P<0.0001) and higher percentages of patients with well-controlled symptoms (urticaria activity score over 7 days (UAS7) ⩽6: 51.9% vs. 11.3% P<0.0001) and complete response (UAS7=0: 35.8% vs. 8.8% P<0.0001) versus placebo. During the 24-week treatment period, 2 (2.9%), 3 (3.4%), 0, and 4 (5.0%) patients in the omalizumab 75-mg, 150-mg, 300-mg, and placebo groups, respectively, experienced a serious adverse event. Omalizumab 300 mg administered subcutaneously every 4 weeks reduced weekly ISS and other symptom scores versus placebo in CIU/CSU patients who remained symptomatic despite treatment with approved doses of H1 antihistamines.

Baseline characteristics of patients enrolled in EXCELS: a cohort study.

BACKGROUND The Epidemiologic Study of Xolair (omalizumab): Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma (EXCELS) is a unique opportunity to evaluate the prospective, long-term clinical safety and effectiveness of the anti-IgE antibody omalizumab (Xolair) in real-world clinical practice. OBJECTIVES To describe the study design and study cohorts of EXCELS at baseline and to compare the characteristics of this population with other large asthma cohorts. METHODS Patients with moderate-to-severe persistent asthma and a positive skin test result or in vitro reactivity to a perennial aeroallergen were eligible for EXCELS. Two cohorts of patients with asthma were enrolled: those treated with omalizumab and those not treated with omalizumab. We analyzed baseline demographic and clinical characteristics, including asthma history and control and allergy history. RESULTS Large proportions of patients enrolled in EXCELS had historically severe and poorly or not well-controlled asthma at the time of enrollment, objective evidence of airway obstruction, a history of long-term oral corticosteroid use, and/or other allergic disorders. Minor differences were observed between the omalizumab and nonomalizumab cohorts. Our total patient cohort was generally similar to other large cohorts. In a subgroup analysis, patients who had received omalizumab within 7 days before enrollment had more severe asthma and greater degrees of impairment at baseline than nonomalizumab patients. CONCLUSIONS This study of baseline characteristics in EXCELS offers a unique opportunity to better understand the history of allergic patients with moderate-to-severe asthma in a real-world treatment setting. This analysis of EXCELS baseline data sets the foundation for long-term assessment of the safety and effectiveness of omalizumab.

Erratum: Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines: A randomized, placebo-controlled study (Journal of Investigative Dermatology (2015) 135 (67-75)) DOI: 10.1038/jid.2014.306)

Citation for pulished version (APA): Saini, S. S., Bindslev-Jensen, C., Maurer, M., Grob, J-J., Bülbül Baskan, E., Bradley, M. S., ... Rosén, K. (2015). Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines: a randomized, placebo-controlled study. Journal of Investigative Dermatology, 135(1), 67-75. https://doi.org/10.1038/jid.2014.306

Longitudinal Changes in Asthma Control with Omalizumab: 2-Year Interim Data from the EXCELS Study

Background. Asthma guidelines emphasize the importance of achieving and maintaining asthma control; however, many patients with moderate to severe asthma fail to achieve adequate control. Objective. This 2-year interim analysis evaluated the longitudinal effects of omalizumab on asthma control in patients treated in real-world clinical practice settings. Methods. EXCELS is an ongoing observational cohort study of approximately 5000 omalizumab-treated and 2500 non-omalizumab-treated patients aged ≥12 years with moderate to severe asthma. Asthma control was measured using the Asthma Control Test (ACT) every 6 months. Results. Subgroups of the omalizumab cohort included those who initiated omalizumab at baseline (new starts, n = 549) and those treated with omalizumab >7 days before baseline (established users, n = 4421). For reference, data are also presented for patients who were not receiving omalizumab prior to or at the time of enrolment (non-omalizumab, n = 2867). Over half of the new starts (54%) achieved improvement in ACT consistent with the minimally important difference (MID, defined as ≥3-point improvement) by Month 6 and this proportion increased throughout the follow-up period, reaching 62% at Month 24. Similar results were observed in patients stratified by moderate and severe asthma. Established users of omalizumab maintained asthma control throughout the observation period. Conclusion. Over a 2-year period, patients initiating omalizumab therapy experienced clinically relevant improvements in asthma control, which were maintained during 2 years of longitudinal follow-up. Established users of omalizumab maintained asthma control over the 2-year period with a small improvement similar to that seen in non-omalizumab users.

Cardiovascular and cerebrovascular events among patients receiving omalizumab: Results from EXCELS, a prospective cohort study in moderate to severe asthma

Background: EXCELS, a postmarketing observational cohort study, was a commitment to the US Food and Drug Administration to assess the long‐term safety of omalizumab in an observational setting, focusing predominantly on malignancies. Objective: The aim of this study was to examine a potential association between omalizumab and cardiovascular (CV)/cerebrovascular (CBV) events in EXCELS. Methods: Patients (≥12 years of age) with moderate to severe allergic asthma and who were being treated with omalizumab (n = 5007) or not (n = 2829) at baseline were followed up for ≤5 years. Analyses included overall CV/CBV events, but focused on the subset of arterial thromboembolic events (ATEs), comprising CV death, myocardial infarction, ischemic stroke, transient ischemic attack, and unstable angina. A prespecified analysis of the end point of ATE was conducted to control for available potential confounders. A blinded independent expert panel adjudicated all events. Results: At baseline, the 2 cohorts had similar demographic characteristics, but severe asthma was more common in the omalizumab versus the non‐omalizumab group (50% vs 23%). Omalizumab‐treated patients had a higher rate of CV/CBV serious adverse events (13.4 per 1,000 person years [PYs]) than did non–omalizumab‐treated patients (8.1 per 1,000 PYs). The ATE rates per 1,000 PYs were 6.66 (101 patients/15,160 PYs) in the omalizumab cohort and 4.64 (46 patients/9,904 PYs) in the non‐omalizumab cohort. After control for available confounding factors, the hazard ratio was 1.32 (95% CI, 0.91–1.91). Conclusion: This observational study demonstrated a higher incidence rate of CV/CBV events in the omalizumab versus the non‐omalizumab cohort. Differences in asthma severity between cohorts likely contributed to this imbalance, but some increase in risk cannot be excluded.