Baseline Disease Duration Poorly Reported in Phase 3 CSU Trials

Despite its relevance to prognosis and treatment response, baseline disease duration is inconsistently reported in phase 3 clinical trials for chronic spontaneous urticaria (CSU), according to a brief report published in Allergy, Asthma & Clinical Immunology.¹

“Despite generally robust methodologies, trials lacked clear definitions of CSU duration, limiting accurate assessment of disease burden,” the authors wrote. CSU, an inflammatory skin disease characterized by recurring wheals or angioedema lasting longer than 6 weeks, places a significant physical, psychological, and economic burden on patients.² The review aimed to evaluate baseline CSU duration and reporting in phase 3 trials.¹

Of 36 unique phase 3 CSU trials identified through a systematic search of MEDLINE and Embase, only 16 (44.4%) reported mean baseline disease duration. Among those that did, the weighted average duration was approximately 5.3 years, reflecting a population with chronic, often treatment-refractory disease by the time of enrollment in advanced therapy trials.

"While CSU involves symptom persistence beyond 6 weeks, average disease duration at enrollment exceeded 5 years, reflecting chronic, often refractory disease among patients accessing advanced therapies," the authors explained, underscoring a disconnect between the minimum diagnostic threshold and the real-world disease burden among trial participants.

The 16 included trials comprised 3980 patients, of whom 68.5% were female, with a mean age of 42.3 years. At baseline, participants had a mean weekly Urticaria Activity Score of 30, and 44.4% of patients presented with angioedema, highlighting a moderate to severe disease burden across the enrolled cohort.

There was variation in disease duration across drug classes. Dupilumab trials reported the longest mean baseline disease duration at 7.18 years compared with 5.97 years for remibrutinib and 5.42 years for omalizumab. The authors suggested this may reflect dupilumab's more recent approval for CSU, meaning enrolled patients had likely exhausted earlier lines of therapy—including omalizumab—before trial participation, rather than any intentional enrollment strategy targeting more refractory patients.

The study also identified temporal trends among the studies. Trials published after 2020 reported shorter average baseline CSU duration (4.82 years) compared with earlier trials (6 years), a shift the investigators attributed in part to evolving clinical practices such as earlier specialist referrals.

Notably, no trial in the review stratified efficacy outcomes by disease duration—a significant gap given that longer disease duration, particularly beyond 10 years, has been associated with greater rates of recurrence and angioedema. The authors also highlighted that definitions of disease duration were frequently left unspecified, further complicating cross-trial comparisons.

The investigators pointed to the immunopathologic relevance of disease duration as additional justification for standardized reporting. Type IIb autoimmune CSU, driven by autoantibody-mediated mechanisms, tends to manifest as more severe, longer-lasting disease with diminished responsiveness to antihistamines and omalizumab. Disease duration may therefore serve as a clinical proxy for underlying immunopathologic subtype, which is a variable with direct implications for treatment selection.

Limitations of the review include methodological heterogeneity across included trials and the absence of participant-level data, which precluded analysis of the distribution of shorter-standing vs longer-standing disease within trial populations.

The authors called for standardized baseline reporting of disease duration alongside demographic characteristics in future CSU trials, noting that this transparency is essential for improving analyses and supporting treatment decisions in a condition with substantial clinical heterogeneity.

“Alongside participant demographics, standardized reporting of baseline disease duration is needed to improve outcome interpretation and inform individualized management,” the authors concluded.

References

1. Gupta S, Rao V, Xiong G, Abu-Hilal M. Baseline disease duration of chronic spontaneous urticaria participants in phase III clinical trials. Allergy Asthma Clin Immunol. Published online March 25, 2026. doi:10.1186/s13223-026-01026-0

2. Tbakhi B, Ware K, Park HS, Bernstein JS, Bernstein JA. An Overview of chronic spontaneous urticaria: diagnosis, management, and treatment. Allergy Asthma Immunol Res. 2025;17(5):531-546. doi:10.4168/aair.2025.17.5.531