Improvement of sleep in patients with chronic idiopathic/spontaneous urticaria treated with omalizumab: results of three randomized, double-blind, placebo-controlled studies

Abstract

Background: Patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) report difficulty with sleep.

Methods: We examined the effect of omalizumab on sleep-related outcomes during 3-6 months omalizumab or placebo treatment and a 16-week follow-up period within three Phase III double-blind randomized placebo-controlled pivotal trials in CIU/CSU: ASTERIA I, ASTERIA II, and GLACIAL. Sleep quality was assessed in all three studies using sleep-related questions included in an electronic diary, the Chronic Urticaria Quality of Life Questionnaire, and the Medical Outcomes Study Sleep Scale. Score changes from baseline in the treatment arms were compared with that in the placebo arm and adjusted for baseline score and weight. We also examined correlations of sleep scores at baseline, week 12, and week 24 and the slopes of change between sleep and itch and hive.

Results: Patients treated with omalizumab reported a larger reduction in sleep problems than those in the placebo arm; omalizumab 300 mg demonstrated the greatest improvement on all sleep components among all treatment arms. The largest reduction in sleep problems was reported within the first 4 weeks of therapy. After treatment discontinuation, sleep quality worsened. Sleep scores demonstrated moderate-to-strong correlation between them, and the change in sleep scores was associated with changes in itch and hives.

Conclusions: Improvement in sleep was reported after the first dose of omalizumab. Sleep continued to improve throughout the active treatment period. Patients receiving omalizumab 300 mg achieved greater improvement in sleep than those in other treatment arms. Trial registration ClinicalTrials.gov, NCT01287117 (ASTERIA I), NCT01292473 (ASTERIA II), and NCT01264939 (GLACIAL).

Keywords: Chronic idiopathic urticaria; Chronic spontaneous urticaria; Omalizumab; Sleep; Sleep quality.

Figures

Fig. 1

Change in UPDD Weekly Sleep Interference Score. a ASTERIA I, b ASTERIA II, and c GLACIAL. Arrows represent omalizumab dosing. Low numbers represent good quality sleep. Least-squares means were derived from a repeated-measures model adjusted for baseline value (less than median, greater than or equal to median) and baseline weight (<80, ≥80 kg). Statistical significance is marked every 4 weeks to minimize the visual burden of the graph. However, the following endpoints demonstrated statistical significance, in addition to the ones marked on the graph: ASTERIA I: all time points for omalizumab 300 mg during treatment and follow-up weeks 25, 34, 37 and 38; weeks 9, 10, 11, and 13 for omalizumab 150 mg; and weeks 26, 27, 29, 30, 31, 33, 34, 37 for omalizumab 75 mg; ASTERIA II: all time points for omalizumab 300 mg during treatment and follow-up weeks 13–15; weeks 1, 2, 3, 5, 6, 7, 9, 10, 11, 13, and 21 for omalizumab 150 mg; and weeks 1, 2, 10, 13, and 21 for omalizumab 75 mg; GLACIAL: all time points during treatment and follow-up weeks 25, 26, 27, 29, 30, and 31 for omalizumab 300 mg. *p < 0.05; **p < 0.001; ***p < 0.01, versus placebo. UPDD Urticaria Patient Daily Diary

Fig. 2

Change in MOS-Sleep Scale, SPI-II score: a ASTERIA I, b ASTERIA II, and c GLACIAL. Arrows represent omalizumab dosing. Low numbers represent good quality sleep. Least-squares means were derived from a repeated-measures model adjusted for baseline value (less than median, greater than or equal to median) and baseline weight (<80, ≥80 kg). *p < 0.05; **p < 0.001; ***p < 0.01, versus placebo. MOS-Sleep Scale Medical Outcomes Study Sleep Scale, SPI-II Sleep Problem Index II

Fig. 3

Change in CU-Q2oL Sleep Problems domain. a ASTERIA I, b ASTERIA II, and c GLACIAL. Arrows represent omalizumab dosing. Low numbers represent good quality sleep. Least-squares means were derived from a repeated-measures model adjusted for baseline value (less than median, greater than or equal to median) and baseline weight (<80, ≥80 kg). *p < 0.05; **p < 0.001; ***p < 0.01, versus placebo. CU-Q2oL Chronic Urticaria Quality of Life Questionnaire

Fig. 4

Correlations between change in UAS7 and change in MOS daytime somnolence: a ASTERIA I, b GLACIAL. UAS7 Weekly Urticaria Activity Score, MOS-Sleep Scale Medical Outcomes Study Sleep Scale, PRO patient-reported outcomes

Fig. 5

Correlations between change in UAS7 and change in MOS sleep disturbance: a ASTERIA I, b GLACIAL. UAS7 Weekly Urticaria Activity Score, MOS-Sleep Scale Medical Outcomes Study Sleep Scale, PRO patient-reported outcomes