[Skip to Navigation]
Views 1,833
Citations 0
Original Investigation
August 25, 2021

Evaluation of Pharmacologic Treatments for H1 Antihistamine–Refractory Chronic Spontaneous Urticaria: A Systematic Review and Network Meta-analysis

Author Affiliations
  • 1Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
  • 2Pharmacoepidemiology and Statistics Research Center, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand
  • 3Division of Dermatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
JAMA Dermatol. Published online August 25, 2021. doi:10.1001/jamadermatol.2021.3237
Key Points

Question  What are the comparative benefits and harms of all available pharmacologic treatments for H1 antihistamine–refractory chronic spontaneous urticaria?

Findings  In this network meta-analysis of 23 randomized clinical trials including 2480 participants, the biologic agents ligelizumab, 72 or 240 mg (large beneficial effect), and omalizumab, 300 or 600 mg (moderate beneficial effect), appeared to be effective treatments for H1 antihistamine–refractory chronic spontaneous urticaria. Alternative treatments with small beneficial effects, namely, dapsone, hydroxychloroquine, cyclosporine, and zafirlukast, can be used.

Meaning  The findings of this meta-analysis may inform international guidelines for the management of chronic spontaneous urticaria that is inadequately controlled with H1 antihistamines and further research in this clinical setting.

Abstract

Importance  The comparative benefits and harms of all available treatments for H1 antihistamine–refractory chronic spontaneous urticaria (CSU) have not been established.

Objective  To evaluate different treatment effects of pharmacologic treatments among patients with H1 antihistamine–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 H1 antihistamines 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 H1 antihistamines. 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.

Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    ×