Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines: a randomized, placebo-controlled study

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01287117.

Figure 1

Patient disposition and study. Gray arrowheads denote study drug treatment on day 1 and at weeks 4, 8, 12, 16, and 20. Black arrow indicates primary end point assessment at week 12. ¹Reasons for screen failure: 14.0% of patients were unwilling to give written informed consent, adhere to the visit schedules, and meet study requirements; 10.5% of patients were not diagnosed with chronic idiopathic urticaria/spontaneous urticaria refractory to H₁ antihistamines at the time of randomization; and 27.5% of patients were categorized as “Other, not defined.” ²Patient did not receive study drug as a result of not meeting all study eligibility criteria and was therefore not included in the modified intention-to-treat population. ³Defined as either the worsening of or no improvement in symptoms. ⁴Seven patients randomized to the omalizumab 75-mg group received at least one dose of omalizumab 150 mg during the treatment period and were included in the omalizumab 150-mg group for the safety and pharmacokinetic analyses.

Figure 2

Mean weekly itch severity score by study week. Error bars represent standard error of the mean. Arrows indicate study drug injection day. Analyzed on the basis of the modified intention-to-treat population with missing weekly scores imputed using baseline weekly itch severity scores.

Figure 3

Responder analysis. P-value versus placebo derived from the Cochran–Mantel–Haenszel χ²-test stratified by baseline UAS7 (<median, ⩾median) and baseline weight (<80 kg, ⩾80 kg). ¹Not evaluated for statistical significance in accordance with the type I error control plan. UAS7, urticaria activity score over 7 days.