Ligelizumab improves sleep among patients with chronic spontaneous urticaria

Patients with chronic spontaneous urticaria who used ligelizumab reported improvements in their sleep quality compared with patients who received omalizumab or placebo, according to a study published in Clinical and Translational Allergy.

Sleep interference impairs cognitive function at work and elsewhere, impacts social lives and increases the risk for comorbidities such as cardiovascular disease and reduced life expectancy, Ana Giménez-Arnau, MD, PhD, professor of dermatology at Universitat Autònoma in Barcelona, and colleagues wrote.

The phase 2b study involved 297 adults with moderate to severe chronic spontaneous urticaria, based on a weekly urticaria activity score (UAS7) of 16 or higher on a scale of 0 to 42.

These patients received 72 mg (n = 84) or 240 mg (n = 85) of ligelizumab (QGE031, Novartis), 300 mg (n = 85) of omalizumab (Xolair; Genentech, Novartis) or placebo (n = 43) every 4 weeks, totaling five injections.

Next, researchers enrolled 226 of these participants with a persistently high UAS7 score of 12 or higher at week 32 in an open-label extension study. These patients received 240 mg of ligelizumab every 4 weeks for 13 treatment cycles, followed by a treatment-free period through week 100.

Participants completed the Urticaria Patient Daily Diary each day. The researchers also tallied UAS7 scores as well as Weekly Sleep Interference Scores (SIS7) and Weekly Activity Interference Scores (AIS7), both ranging from 0 to 21, with higher scores indicating worse results.

SIS7 scores were balanced between the treatment arms at baseline, although nearly 12% of patients in each cohort had a SIS7 score greater than 17, and most had an SIS7 score between 3 and 17.

At week 12, least square (LS) mean changes from baseline in SIS7 scores included 7.84 (standard error [SE], 0.58) for 72 mg and 7.55 (SE, 0.61) for 240 mg of ligelizumab, 6.98 (SE, 0.6) for omalizumab and 5.85 (SE, 0.81) for placebo. At week 20, results included 8.25 (SE, 0.58) for 72 mg and 8.22 (SE, 0.6) for 240 mg of ligelizumab, 7.44 (SE, 0.6) for omalizumab and 5.51 (SE, 0.8) for placebo.

At week 20, 64.3% of the patients on 72 mg ligelizumab, 63.5% of the patients on 240 mg ligelizumab, 61.2% of the patients on omalizumab and 51.2% of the patients receiving placebo reported limited or no sleep interference.

This effect on SIS7 scores persisted through the treatment-free follow-up period between weeks 20 and 32, and the patients receiving 240 mg of ligelizumab took longer to return to baseline compared with the other participants.

The participants in the extension study also saw sustained improvements in their sleep interference scores from baseline (3.91; SE, 0.31) for the full 52-week treatment period, with a gradual increase in SIS7 scores during the treatment-free follow-up period through week 100.

Similarly, LS mean changes from baseline in AIS7 scores included were higher for ligelizumab (72 mg, 8.25; SE, 0.57; 240 mg, 8.25, SE, 0.59) than omalizumab (7.3; SE, 0.6) and placebo (5.62; SE, 0.79) at week 12, with sustained improvements at week 20 and throughout the extension study’s treatment period.

Researchers also used Work Productivity and Activity Impairment-Chronic Urticaria scores to assess impact on work, including absenteeism, presenteeism, overall work impairment (combining absenteeism and presenteeism scores) and activity impairment. Higher scores reflected greater impairment and less productivity.

Participants on 240 mg of ligelizumab experienced the highest improvements in Overall Work Impairment scores at week 12, at 30.76 (SE, 3.71), compared with 28.96 (SE, 3.73) for 72 mg of ligelizumab, 25.74 (SE, 3.91) for omalizumab and 20.13 (SE, 5.1) for placebo.

Plus, patients assigned 72 mg (P = .004) and 240 mg (P = .003) of ligelizumab saw improvements in presenteeism along with improvements in overall work impairment (P = .003 and P = .002, respectively) at week 12 compared with placebo. Participants in the extension study experienced similar improvements as well.

The researchers noted the importance of complete urticaria control and called for further phase 3 studies on its effects on sleep as well as considering sleep quality in integrated treatment approaches.