Ligelizumab, omalizumab most effective in refractory chronic spontaneous urticaria

Ligelizumab and omalizumab were found to be the most effective treatments for adolescent and adult patients with chronic spontaneous urticaria who had failed to respond to H1 antihistamines, according to a study.

“The comparative benefits and harms of all available treatments for H1 antihistamine–refractory chronic spontaneous urticaria have not been established,” Surapon Nochaiwong, PharmD, of the department of pharmaceutical care at Chiang Mai University in Chiang Mai, Thailand, and colleagues wrote.

The analysis included Medline, Embase, PubMed, Cochrane Library, Web of Science, Scopus and Cinahl databases, along with Google Scholar, ongoing trials and preprint reports. Randomized clinical trials from inception through April 19, 2021, were included.

The researchers assessed treatment effects — including both benefits and harms —of various pharmacologic therapies used to treat adolescents and adults who had failed to mount an adequate response to H1 antihistamines.

The final analysis yielded data for 2,480 participants from 23 trials that included the primary outcome of changes in urticaria symptoms from baseline and unacceptability of treatment. Eighteen different interventions and dosages were studied, in addition to placebo cohorts.

The strongest effect was seen in ligelizumab (Novartis) at a dose of 72 mg, which yielded a standardized mean difference (SMD) for change in urticaria symptoms of 1.05 (95% CI, 1.37 to 0.73). Ligelizumab at 240 mg also yielded a positive change in symptoms (SMD = 1.07; 95% CI, 1.39 to 0.75). The researchers described the impact of ligelizumab as a “large beneficial effect.”

Similar outcomes as assessed by standardized mean difference for change in urticaria symptoms were reported for omalizumab (Xolair, Genentech) at both the 300 mg dose (SMD = 0.77; 95% CI, 0.91 to 0.63) and the 600 mg dose (SMD = 0.59; 95% CI, 1.10 to 0.08). The researchers noted a “moderate beneficial effect” for omalizumab.

The researchers did not observe any significant differences in treatment unacceptability for these two drugs.

Regarding other therapies that underwent analysis, dapsone, hydroxychloroquine, cyclosporine and zafirlukast (Accolate, Annora Pharma) were associated with a “small beneficial effect.” In addition, a small benefit was reported for ligelizumab 24 mg and omalizumab 150 mg.

However, the researchers do not recommend these treatments due to uncertain efficacy outcomes or higher risk for adverse events. Moreover, they said the studies investigating these treatments were varied in terms of magnitude of effect size and evidence certainty.

“The findings in this meta-analysis suggest that the biologic agents ligelizumab, 72 mg or 240 mg, and omalizumab, 300 mg or 600 mg, can be recommended as effective treatments for patients with CSU who have had an inadequate response to H1 antihistamines,” the researchers wrote. “Head-to-head trials with high methodologic quality and harmonized design and outcome definitions are needed to help inform subsequent international guidelines for the management of [chronic spontaneous urticaria].”