Evaluation of Pharmacologic Treatments for H<inf>1</inf>Antihistamine-Refractory Chronic Spontaneous Urticaria: A Systematic Review and Network Meta-analysis

Abstract

Importance: The comparative benefits and harms of all available treatments for H1antihistamine-refractory chronic spontaneous urticaria (CSU) have not been established. Objective: To evaluate different treatment effects of pharmacologic treatments among patients with H1antihistamine-refractory CSU. Data Sources: Searches were conducted of MEDLINE, Embase, PubMed, Cochrane Library, Web of Science, Scopus, and CINAHL from inception to April 19, 2021, with no language restrictions. Gray literature from Google Scholar, ongoing trial registers, and preprint reports was added to the searches of electronic databases. Study Selection: Randomized clinical trials using validated measurement tools that investigated the benefits and harms of pharmacologic treatments among adolescent or adult patients with CSU who had an inadequate response to H1antihistamines were screened for inclusion independently by 2 investigators. Data Extraction and Synthesis: Two investigators independently extracted study data according to the predefined list of interests. A random-effects model was used to calculate the network estimates reported as standardized mean differences and odds ratios with corresponding 95% CIs. Main Outcomes and Measures: The primary outcomes that reflect the patient's perspective included changes in urticaria symptoms from baseline and unacceptability of treatment (all-cause dropouts). Results: Twenty-three randomized clinical trials with 2480 participants that compared 18 different interventions or dosages and placebo were included. The standardized mean differences for change in urticaria symptoms were -1.05 (95% CI, -1.37 to -0.73) for ligelizumab, 72 mg; -1.07 (95% CI, -1.39 to -0.75) for ligelizumab, 240 mg; -0.77 (95% CI, -0.91 to -0.63) for omalizumab, 300 mg; and -0.59 (95% CI, -1.10 to -0.08) for omalizumab, 600 mg. No significant differences in treatment unacceptability were observed. With respect to benefits and harms, the network estimates illustrated that the most efficacious treatments were achieved with ligelizumab, 72 or 240 mg (large beneficial effect) and omalizumab, 300 or 600 mg (moderate beneficial effect). Conclusions and Relevance: The findings in this meta-analysis suggest that the biologic agents ligelizumab, 72 or 240 mg, and omalizumab, 300 or 600 mg, can be recommended as effective treatments for patients with CSU who have had an inadequate response to H1antihistamines. 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 CSU.