Comparative efficacy and safety of biologics and systemic immunomodulatory treatments for chronic urticaria: Systematic review and network meta-analysis
Bibliographic record
Abstract
BACKGROUND: Chronic urticaria is a common skin condition characterized by itchy wheals (hives), angioedema, or both, lasting for 6 weeks or more. Beyond antihistamines, multiple systemic treatments are available, but there is uncertainty regarding their comparative effects on chronic urticaria outcomes. OBJECTIVE: We systematically synthesized the comparative benefits and harms of systemic treatments for chronic urticaria. METHODS: As part of updating the AAAAI/ACAAI JTFPP chronic urticaria guidelines, we searched Medline, Embase, Central, Chinese Biomedical Databases (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and Wanfang from inception to February 4, 2025, for randomized trials addressing systemic immunomodulatory treatments, including phototherapy, for chronic urticaria. Paired reviewers screened records, extracted data, and assessed risk of bias. Random effects Bayesian network meta-analyses addressed urticaria activity (comprising itch and wheal scores), angioedema activity, health-related quality of life, and adverse events. The GRADE approach informed certainty-of-evidence ratings (PROSPERO: CRD42023429819). RESULTS: We included 93 studies (n = 11,398; mostly adult and adolescent participants across 83 randomized trials and 10 nonrandomized studies) that evaluated 42 interventions. With high certainty, standard-dose omalizumab (300 mg every 4 weeks) and remibrutinib are among the most effective for improving multiple patient-important outcomes. The safety profile of remibrutinib, however, is less certain. Dupilumab improved urticaria activity, but its impact on quality of life is uncertain, and no dupilumab trials addressed angioedema activity. Cyclosporine may be among the most effective for improving urticaria activity but may be among the most harmful in increasing the frequency of any adverse events. Azathioprine, dapsone, hydroxychloroquine, mycophenolate, sulfasalazine, and vitamin D may improve outcomes, while benralizumab, quilizumab, and tezepelumab may not differ from placebo, though the evidence is uncertain. Findings were consistent across age groups and baseline severity, and were robust to subgroup analyses. CONCLUSIONS: Among individuals with chronic urticaria refractory to antihistamines, standard-dose omalizumab and remibrutinib are among the most effective drugs across multiple patient-important outcomes with a favorable safety profile across the studied duration. Cyclosporine may be effective but may be among the most harmful. Dupilumab improves itch and wheals, but it is uncertain whether it improves angioedema or quality of life. Lower doses of omalizumab are of intermediate effectiveness and favorable safety. The net benefit of conventional immunosuppressants is uncertain.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.023 | 0.056 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.022 | 0.034 |
| Bibliometrics | 0.009 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".