Eric Karlin, MD

Experts discuss which outcome instruments are most useful in routine clinical practice and address how patients' tendency to underreport disease burden before experiencing effective treatment affects baseline severity assessment and escalation decision-making.

Outcome Instruments in Practice and Baseline Underreporting in Untreated CSU

Chronic spontaneous urticaria is assessed through several validated instruments that measure distinct but related dimensions of disease: the daily UAS and UAS7 quantify objective disease activity through hive count and itch severity; the Urticaria Control Test (UCT) captures the patient's own perception of disease control; and the Dermatology Life Quality Index (DLQI) measures the broader impact of disease on daily functioning. The updated international guidelines recommend UAS7 and UCT as primary monitoring tools for CSU, with provocation thresholds added for inducible subtypes. In clinical practice, however, implementing a multi-instrument assessment consistently across a busy practice requires deliberate workflow integration, and not all instruments are equally accessible or practical in every clinical setting.

A recurring pattern across multiple CSU data sets — including the REMIX-1/-2 remibrutinib analyses — is that the correlation between UAS7 and UCT is moderate at baseline but strengthens substantially once effective treatment is underway. This dynamic reflects a clinically important phenomenon: patients who have lived with poorly controlled CSU for months or years may lack a meaningful reference point for what disease control actually feels like, and as a result may underreport the degree to which their disease is affecting them at the time of initial evaluation. The implication is that pre-treatment severity assessments, while necessary, may systematically underestimate true disease burden — and that the full impact of untreated CSU may only become legible to both patient and clinician retrospectively, once effective therapy has established a new baseline for comparison.

In this final segment of the video discussion on CSU management updates, Steve Dorman, MD, notes that this underreporting dynamic has direct implications for escalation decisions: a patient whose baseline UCT or UAS7 appears only moderately abnormal may in fact be carrying a heavier burden than the scores reflect, and clinicians should weigh that possibility when deciding whether to advance therapy. Eric Karlin, MD, adds that in his practice he captures both UAS7 and UCT routinely, finding that the 2 instruments together provide a more complete picture than either alone — and that watching the UCT rise in parallel with falling UAS7 scores as treatment takes effect is itself one of the more reliable signals that a step-up therapy is producing genuine disease control rather than partial or transient relief.

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Experts review a phase 2 exploratory analysis of barzolvolimab in CSU, examining off-treatment efficacy at 28 weeks after the final dose, complete response rates, and quality-of-life outcomes among patients who achieved well-controlled disease after 52 weeks of treatment.

Barzolvolimab Post-Treatment Durability —Off-Treatment Data, Complete Response Rates, and Quality-of-Life Outcomes

Among the most clinically striking findings to emerge from recent urticaria research is evidence that therapeutic benefit in CSU may persist substantially beyond the cessation of active treatment — a pattern observed in a phase 2 exploratory analysis of barzolvolimab, an anti-KIT monoclonal antibody targeting the mast cell stem cell factor receptor, presented at the 2026 American Academy of Allergy, Asthma & Immunology meeting. The analysis examined patients who completed 52 weeks of barzolvolimab — at doses of either 150 mg every 4 weeks or 300 mg every 8 weeks — and achieved at least well-controlled disease, defined as a UAS7 of 6 or less, at week 52. Of 55 qualifying patients, 48 had data available at week 76. At study entry, 71% of this subgroup had severe disease and the mean UAS7 was 31.5 at baseline — a substantially burdened population. By week 52, 87% had achieved a complete response (UAS7 = 0) and 13% had well-controlled disease.

The off-treatment follow-up data are notable on multiple levels. At week 76 — 28 weeks after the final dose — 50% of patients maintained a complete response and 19% maintained well-controlled disease, with approximately 69% maintaining at least well-controlled disease without any ongoing therapy. Among those sustaining complete response at week 76, the mean UAS7 was 0.4, the mean Dermatology Life Quality Index (DLQI) was 1.17, and 83% had a DLQI of 0 or 1, indicating no meaningful impact of disease on quality of life. This off-treatment durability was observed despite confirmed clearance of barzolvolimab from circulation and normalization of serum tryptase — a mast cell biomarker — findings the study authors characterize as consistent with disease modification rather than symptom suppression alone, and which provide the scientific basis for the agent's ongoing phase 3 development.

In this segment of the video discussion on CSU management updates, Steve Dorman, MD, walks through the week 76 findings in detail, emphasizing that the persistence of complete response nearly 7 months after the last dose — in a population that entered the study with severe, long-standing disease — is not a pattern previously observed with any other agent in the CSU therapeutic landscape. The normalization of serum tryptase alongside the clearance of drug from circulation is a particularly important mechanistic signal, as it suggests that the disease-modifying effect is not dependent on ongoing drug exposure. Eric Karlin, MD, frames the DLQI outcomes as the patient-centered complement to the activity scores: an 83% rate of DLQI 0 or 1 at week 76 in patients who are no longer on therapy describes a population that has, by their own report, effectively returned to normal life.

Experts review REMIX-1/-2 pooled data on daily Urticaria Activity Score through day 7 and UCT progression through week 52, examining what daily resolution adds to the understanding of BTK inhibition onset and how the trajectory of disease control informs follow-up conversations with patients.

New Remibrutinib Data — Daily Disease Activity, Severity Band Shifts, and UCT Trajectory Through Week 52

Evaluating treatment response in chronic spontaneous urticaria has historically relied on the Urticaria Activity Score over 7 days (UAS7), a weekly composite of hive count and itch severity. Pooled data from the REMIX-1 and REMIX-2 phase 3 studies introduce a complementary daily UAS — derived from averaged morning and evening hive count and itch severity reports — that allows a more granular view of symptom trajectory from the first day of treatment. By day 7, mean daily UAS in the remibrutinib arm had fallen to 2.25, within the well-controlled threshold of less than 2.5, compared with 3.49 in the placebo group — a level consistent with moderate CSU symptoms. The categorical distribution shift is equally instructive: 37% of remibrutinib-treated patients had moved into the lowest UAS severity band by day 7, representing no or minimal symptoms, versus 9.7% on placebo. This means more than 1 in 3 patients on remibrutinib had achieved near-complete symptom resolution within the first week of treatment.

The REMIX data also capture the longer arc of disease control through the Urticaria Control Test (UCT), a validated patient-reported instrument with a well-controlled threshold of 12. At week 2, mean UCT in the remibrutinib arm was 10.5, compared with 7.3 in the placebo group — meaningfully improved but not yet at threshold. By week 12, mean UCT had risen to 11.4 in the remibrutinib group, approaching the well-controlled threshold closely. These improvements were sustained through week 52, and patients who crossed over from placebo to remibrutinib at week 24 achieved comparable UCT outcomes — reinforcing the consistency of the therapeutic effect regardless of when treatment was initiated. Together, the day-7 daily UAS data and the week-2 through week-52 UCT trajectory describe a therapy whose benefits are rapid in onset and durable over time.

In this segment of the video discussion on CSU management updates, Steve Dorman, MD, situates both data sets within the framework of patient communication. The day-7 daily UAS findings provide a concrete and evidence-supported basis for setting early expectations at the time of prescribing, while the UCT progression from week 2 through week 52 offers a practical scaffold for follow-up visits — a patient who has moved from a baseline UCT of 5 to 10.5 at week 2 has experienced a substantial transformation in disease burden even before crossing the formal well-controlled threshold, and framing that progress explicitly is an important part of sustaining engagement with therapy. Eric Karlin, MD, adds that capturing both UAS7 and UCT in practice gives the initiation and follow-up conversation a dual anchor — one instrument quantifying what the clinician observes and the other giving the patient's own experience a structured voice.

Experts discuss the most clinically meaningful changes in the 2026 international urticaria guideline update, including the expanded step-up therapy framework and the current limitations of biomarkers in routine CSU practice.

The 2024 International Guideline Update — What Changed and Why It Matters

The 2026 international urticaria guideline update represents the first major revision since 2022 and reflects input from more than 200 experts across 59 countries. Among its most clinically consequential changes is the positioning of omalizumab, dupilumab, and remibrutinib together as add-on options for patients with CSU who remain symptomatic despite high-dose antihistamine therapy. This represents a meaningful expansion from prior iterations, in which omalizumab stood largely alone at that step in the algorithm. Within the updated framework, omalizumab is represented by a solid line while dupilumab and remibrutinib appear with dotted lines — a distinction the guideline authors clarify reflects evidence maturity rather than any hierarchy of efficacy. Use of any of these agents may be off-label depending on jurisdiction.

The update also addresses the role of biomarkers in CSU management with notable directness. Despite growing investigation into markers including total IgE levels, thyroid antibodies, and other candidate measures, the guidelines explicitly state that no biomarker has achieved sufficient predictive accuracy for routine clinical use. One relevant clinical signal preserved in the document is the association between low IgE values and attenuated response to omalizumab — a finding that, while not yet actionable as a formal decision rule, can meaningfully inform the therapeutic conversation with individual patients. The absence of a validated predictive biomarker remains one of the more consequential unmet needs in the field, and the guidelines recommend limiting baseline laboratory evaluation to a differential blood count and CRP and/or ESR, with total IgE and anti-TPO antibodies reserved for specialized care settings.

In this video discussion on CSU management updates, Eric Karlin, MD, an allergist/immunologist with Allergy Partners of Hampton Roads in Williamsburg, Virginia, and Steve Dorman, MD, a board-certified allergist/immunologist and clinical research investigator on clinical faculty at the University of Florida College of Medicine, examine the practical implications of these guideline changes. Dorman underscores the historical significance of having 3 agents positioned at the same algorithmic step, noting that clinicians who trained in an era when cyclosporine was the only off-label recourse for antihistamine-refractory CSU will recognize how substantially the landscape has shifted. Both experts emphasize that the visual distinction between the solid and dotted lines in the guideline algorithm is a point of frequent misinterpretation in practice and should be communicated carefully to colleagues evaluating the evidence.

Eric Karlin, MD

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