CSU congress updates

EAACI 2025: Advances and clinical gaps in CSU

What new data from the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2025 in Glasgow, UK, could shift how chronic spontaneous urticaria (CSU) is diagnosed and treated?

The latest results, summarized below, highlighted long-term symptom control, angioedema management, and persistent care gaps.

To hear expert insights on this changing CSU treatment landscape, check back soon to watch our interview with Gülseren Tuncay (Hacettepe University School of Medicine, Ankara, Türkiye) under EAACI 2025: Expert reflections.

Long-term CSU control with barzolvolimab after treatment cessation

Barzolvolimab shows sustained disease control after discontinuation in a phase 2 study of 189 patients with antihistamine-refractory CSU.

At week 76 (28 weeks after the final dose), 41% of patients who had received 150 mg every 4 weeks and 35% of those on 300 mg every 8 weeks had a Weekly Urticaria Activity Score (UAS7) of 0. Well-controlled disease (UAS7 ≤6) was seen in 56% and 47%, respectively.

There were no new safety signals during the follow-up period. Most adverse events were mild, and included hair color changes, neutropenia/neutrophil count decrease, urticaria, and skin hypopigmentation.

Presenter Ana Maria Giménez-Arnau (Pompeu Fabra University, Barcelona, Spain) said that these data indicate the potential of barzolvolimab to shift the treatment goals for CSU from symptom control to disease modification.

Emerging treatments offer sustained angioedema control

New data show the potential for two in-development treatments to offer long-term control of angioedema in addition to urticaria in patients with CSU.

The data for barzolvolimab come from a phase 2 trial in which 149 patients with baseline angioedema received active treatment. At week 52, the mean reductions in Angioedema Activity Score over 7 days (AAS7) were 86.3% for those given 150 mg every 4 weeks and 82.4% for patients given 300 mg every 8 weeks.

Furthermore, Martin Metz (Charité – Universitätsmedizin Berlin, Germany) reported that a corresponding 92.5% and 88.9% of patients achieved a ≥8-point AAS7 improvement, considered to be the minimal clinically important difference.

Among those re-randomized from placebo or lower-dose active treatment, 80.4% (150 mg) and 90.7% (300 mg) also reached this threshold. At week 52, up to 77% of patients were free of symptoms, with an average of 238 angioedema-free days.

The findings for remibrutinib are based on a pooled analysis of patients with baseline angioedema from the phase 3 REMIX-1 and -2 trials – 374 of these took remibrutinib 25 mg twice a day for the full 52 weeks and 169 started on placebo and switched to remibrutinib at week 24.

Presenter Michihiro Hide (Hiroshima City Hiroshima Citizens Hospital, Japan) revealed that symptom improvement began by week 1 and then remained stable. At week 24, mean AAS7 reductions were 36.4 for remibrutinib versus 24.2 for placebo, and 82% of all patients achieved AAS7=0 at week 52.

Remibrutinib efficacy consistent across IgE levels

Opening his presentation, John Reed (University of Oxford, UK) noted that the type I (autoallergic) CSU endotype is characterized by normal to high levels of total immunoglobulin E (IgE), whereas the type IIb (autoimmune) endotype is marked by low levels.

In the absence of a validated biomarker for CSU, IgE has potential due to its “accessibility and low cost,” he said, noting evidence that it may predict response to omalizumab.

However, his team’s analysis, which again involved pooled data from REMIX-1 and -2, shows that remibrutinib treatment led to “early and sustained symptom improvements” versus placebo treatment, regardless of IgE subgroup at baseline.

Among 912 patients who were symptomatic despite second-generation antihistamines, remibrutinib 25 mg twice daily for 24 weeks led to average reductions in UAS7 scores of 26.3 and 21.0 for those with IgE of ≤43 IU/mL and >43 IU/mL, respectively, and of 24.2 and 20.6 for those with IgE of ≤100 IU/mL and >100 IU/mL, respectively.

Mental health burden in patients with CSU

A retrospective insurance claims analysis of 224,958 adults with CSU in the USA shows increased mental health and sleep-related comorbidities following diagnosis.

Tara Raftery (Novartis Pharmaceuticals, Dublin, Ireland) reported that the proportion of patients with ≥1 mental health condition rose from 40.6% at baseline to 56.3% during a median 2.38 years of follow-up.

Anxiety was the most frequently recorded condition (35.6%), followed by chronic fatigue (31.4%) and depression (23.6%). Sleep-related diagnoses increased from 8.8% to 15.4%, with insomnia reported in 13.4% of patients post-diagnosis.

These diagnoses were more frequent in symptomatic patients than in those with controlled disease, and being symptomatic was associated with increased health resource utilization and medication use. Antidepressant claims were recorded for 42.4% of symptomatic patients versus 31.1% of patients with controlled disease; sleep aids were used by 5.2% and 3.3%, respectively.

Gaps in CSU awareness and guideline use among GPs in Italy

An additional problem for patients with CSU has been highlighted by a national survey in Italy showing barriers to CSU diagnosis and management in general practice.

Of the 95 general practitioners (GPs) who completed the survey, 60% reported having little to no knowledge of CSU management, and 61% were unaware of existing CSU treatment guidelines.

In the previous 6 months, GPs had referred an average of three patients with suspected CSU to specialists. Median waiting times for specialist appointments were 100 days in the national health system versus just 10 days in private practice.

Presenting the findings, Riccardo Asero (Clinica San Carlo, Paderno Dugnano, Italy) said that only 15% of GPs reported using patient-reported outcomes in routine clinical practice. However, these individuals reported higher rates of CSU knowledge and guideline awareness and use than other survey respondents.

“Results of REMIX studies were undoubtedly valuable as they demonstrated full disease control of up to 80%.” Gülseren Tuncay (Charité – Universitätsmedizin, Berlin, Germany) discusses results from the REMIX-1 and -2 studies presented at the 2025 European Academy of Allergy and Clinical Immunology (EAACI) Congress. View transcript.

“Results from the RIFA-CU study highlight the need for a comprehensive, multidisciplinary approach to CSU care.” Gülseren Tuncay (Charité – Universitätsmedizin, Berlin, Germany) discusses how findings of the first, large, multinational case–control study, RIFA-CU, should guide future changes in the management of patients with CSU. View transcript.

Gülseren Tuncay (Charité – Universitätsmedizin, Berlin, Germany) sheds light on the patient burden associated with diagnosing CSU, drawing on key findings from the BRIDGE study presented at EAACI 2025. View transcript.

Gülseren Tuncay (Charité – Universitätsmedizin, Berlin, Germany) summarizes the findings of an observational study that utilized data from the CURE registry to investigate different phenotypes and better understand their role in the treatment of CSU. View transcript.

EADV 2025: Insights from REMIX-1 and REMIX-2

Key sessions at the European Academy of Dermatology and Venereology (EADV) Congress 2025 highlighted advances in chronic spontaneous urticaria (CSU) management, including:

• Targeting immunoglobulin (Ig)G in CSU with remibrutinib
• Clinical outcomes from the REMIX-1 and REMIX-2 trials
• Impact of baseline characteristics and demographics

Targeting IgG in CSU with remibrutinib

Martin Metz (Charité – Universitätsmedizin Berlin, Germany) presented late-breaking data from the REMIX-1 and REMIX-2 trials, focusing on remibrutinib’s ability to reduce specific IgG autoantibody levels in people with CSU.

The 397 remibrutinib-treated patients included in the biomarker analysis were a mean age of 46  years and were predominantly non-Asian (67.4–87.5% across the two trials). Their Chronic Urticaria Index (CUI) positivity rates were approximately 33% in both trials, which was higher than the rates of 22.2% and 29.0% observed in the placebo groups.

Remibrutinib reduced specific autoantibody levels at week 24

Metz and colleagues assessed levels of autoantibodies, soluble CD23, and B-cell subsets at multiple timepoints, integrating biomarker data with clinical outcomes and CUI status to explore remibrutinib’s immunomodulatory effects.

In subgroup analyses, the researchers found that CUI-positive patients had elevated CSU-linked autoantibodies at baseline, which significantly decreased with remibrutinib treatment by week  24 – “showing that this is a true autoimmune disease,” as Metz noted.

Biomarker and flow cytometry analyses confirmed reductions in key autoantibodies, including those against high-affinity IgE receptor or thyroid peroxidase, and thyroglobulin, in CUI-positive patients.

Remibrutinib treatment did not affect total B-cell counts, but led to a significant reduction in non-switched memory B cells over 52 weeks. This effect was not observed in class-switched memory B cells. Treatment also reduced levels of soluble CD23; these were elevated in CUI-positive patients at baseline but were in line with levels in healthy volunteers after 52 weeks of remibrutinib treatment.

Metz wrapped up the session by emphasizing the need for further analysis to determine whether remibrutinib’s effect on autoantibody levels is associated with disease modification in CSU.

Remibrutinib treatment delivers rapid relief

Metz presented additional findings from the REMIX-1 and REMIX-2 trials, looking in this instance at the timing of treatment response.

Remibrutinib delivers rapid and sustained symptom control in antihistamine-refractory CSU

The trials together included 900 adults, who were a mean age of 43 years. Two-thirds were female, with average body mass index of 27 kg/m² and a disease duration of approximately 5–6  years.

In the pooled analysis, remibrutinib demonstrated robust efficacy in adults with CSU inadequately controlled by second-generation antihistamines. By week 24, 70% of patients receiving remibrutinib achieved well-controlled disease, defined as a Weekly Urticaria Activity Score (UAS7) of ≤6, compared with 49% in the placebo group.

Notably, well-controlled urticaria (UAS7 ≤6) was observed in 58% of remibrutinib-treated patients by week 3 (median time to UAS7 ≤6 of 3 weeks), versus 18% in the placebo arm (median time, 9 weeks).

Likewise, complete symptom control (UAS7=0) was reported in 38% of remibrutinib-treated patients by week 3 (median time, 5 weeks), versus 5% in the placebo arm (median time, 12 weeks).

Remibrutinib demonstrated a favorable safety profile, supporting its potential as a well-tolerated oral treatment option for patients who are unresponsive to antihistamines.

Impact of baseline characteristics and demographics

Another analysis of REMIX-1 and REMIX-2, presented by Bin Yang (Southern Medical University, Guangzhou, China), focused on the efficacy of remibrutinib across various demographic and baseline characteristics.

Remibrutinib demonstrated consistent efficacy across multiple patient subgroups

Across all subgroups, a greater proportion of patients treated with remibrutinib achieved well-controlled disease (UAS7 ≤6) compared with those receiving placebo. Notable subgroup outcomes included:

• CSU duration ≤1 year: 50% vs 22%
• CSU duration >5 years: 48% vs 21%
• Prior angioedema: 57% vs 23%
• Moderate disease: 54% vs 23%
• Severe disease: 46% vs 22%

Yang concluded by emphasizing the consistent improvement in CSU symptoms, regardless of baseline demographics, disease characteristics, or prior antihistamine use.

Navigating CSU: Timing and novel agents

Updates from the European Academy of Dermatology and Venereology (EADV) 2025 Congress on managing chronic spontaneous urticaria (CSU) included:

• The importance of early intervention in CSU disease management
• Barzolvolimab efficacy across immunoglobulin (Ig)E profiles
• Comparative insights on advanced therapies

Timing matters: Early vs late biologic use in CSU

Merin Kuruvilla (Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA) presented findings from a real-world analysis conducted in the USA, examining healthcare resource utilization (HCRU) among individuals with CSU, stratified by time to advanced treatment escalation.

She began by noting that, despite guideline recommendations, a substantial proportion of patients with uncontrolled CSU are not escalated to advanced therapies.

The analysis revealed several key differences between early (≤3 months between diagnosis and biologic therapy) and late (>3 to ≤12 months) treatment groups. Following exclusion of outliers, 6,734 patients were included in the HCRU analysis: 3,589 (53.3%) in the late initiation group and 3,145 (46.7%) in the early initiation group. Baseline characteristics were comparable between the two groups.

A higher proportion of patients in the late initiation group used corticosteroids post-index (88.5%) compared with those in the early initiation group (81.6%). Similarly, lack of disease control post-index was more common in the late-initiation group (79.4%) versus the early group (70.7%).

Notably, patients with late biologic initiation had higher rates of HCRU, including inpatient admissions (38.4% vs 36.6%), emergency department visits (29.4% vs 25.5%), and urgent care visits (22.5% vs 20.7%) compared with those who escalated treatment earlier.

Kuruvilla said that the reduced corticosteroid and healthcare resource use in patients with early biologic initiation “is suggestive of greater disease control and highlights the value of timely treatment escalation.”

Barzolvolimab improves CSU across IgE profiles

Martin Metz (Charité – Universitätsmedizin, Berlin, Germany) presented an analysis of a phase 2 study evaluating the efficacy of the receptor tyrosine kinase inhibitor barzolvolimab in relation to baseline IgE levels at weeks 12 and 52. He noted that low circulating IgE levels have been linked to poor response to anti-IgE therapies.

A total of 207 patients participated in the study, 72% of whom had severe disease symptoms at baseline. They were stratified into those with normal/high IgE levels (≥40 IU/mL) at baseline and a low IgE group (<40  IU/mL), with each group receiving either placebo, 150 mg barzolvolimab every 4 weeks, or 300 mg every 8 weeks.

Barzolvolimab treatment led to similar rates of well-controlled disease (Urticaria Activity Score over 7  days [UAS7] ≤6) at both 12 and 52 weeks across patients with low and normal/high baseline IgE levels, demonstrating consistent efficacy regardless of IgE subgroup.

Metz emphasized the importance of “putting the mast cells in the center of the pathogenesis of urticaria,” highlighting their pivotal role in disease mechanisms. He concluded that barzolvolimab is a promising treatment option for patients with moderate to severe CSU, regardless of underlying endotype.

CSU treatments compared: Omalizumab, dupilumab, remibrutinib

Grace Xiong (Michael G. DeGroote School of Medicine, Hamilton, Ontario, Canada) presented results from a network meta-analysis of clinical trials, which aimed to compare the effectiveness of omalizumab, dupilumab, and remibrutinib.

The study included 4,913 participants with a mean age of 43 years (range, 12–75). Of the 4,615 with recorded sex, 23.2% were male and 76.8% female. The majority of participants were taking omalizumab, mostly at a dose of 300 mg (n=2,088), with 124 taking dupilumab and 657 remibrutinib.

Omalizumab 300 mg emerged as the most effective treatment, delivering the greatest reductions in UAS7 and Itch Severity Score over 7 days, and the highest odds of symptom remission and disease control at both 12 and 24 weeks. Lower doses of omalizumab demonstrated early benefit at week 12, but these effects were not sustained through week 24.

Remibrutinib administered at 25 mg twice daily showed the strongest improvements in quality of life and ranked second in symptom reduction and odds of symptom remission at week 12.

Dupilumab 300 mg administered every 2 weeks offered meaningful itch relief by week 24, though its overall efficacy was more variable.

The researchers concluded that while omalizumab 300  mg every 4  weeks continues to demonstrate the strongest efficacy among advanced therapies for CSU, emerging options such as remibrutinib and dupilumab show promise, particularly for patients unresponsive to omalizumab. Further data are needed to clarify the role of these treatments in specific patient subgroups.