15% of Omalizumab-Treated CSU Patients Required Dose Escalation in Real-World Study

For patients with chronic spontaneous urticaria (CSU) who fail standard-dose omalizumab, identifying who will need dose escalation before treatment begins remains a persistent clinical challenge.¹ A recently published retrospective real-world study offers new data on that question — and points to elevated D-dimer as the only independent predictor of high-dose omalizumab (HDO) requirement.²

The study, conducted at Bezmialem Vakıf University in Turkey, analyzed clinical and laboratory parameters in 199 adult CSU patients who were refractory to 4-fold second-generation H1 antihistamines and treated with omalizumab. Researchers compared outcomes between patients maintained on standard-dose omalizumab (SDO; 300 mg every 4 weeks) and those who required escalation to HDO (450–600 mg every 4 weeks).

Who Required Dose Escalation?

Of the 199 patients, 31 (15.5%) required escalation to high-dose therapy — a rate consistent with prior real-world studies reporting HDO use in roughly 12% to 27% of omalizumab-treated CSU patients.

In univariate analyses, several variables were associated with HDO use. Patients in the HDO group were significantly older (mean age 45.94 years vs. 41.29 years in the SDO group; p = 0.050) and had significantly higher mean BMI (28.3 vs. 25.9 kg/m²; p = 0.016). Angioedema was substantially more prevalent among HDO patients (45.2% vs. 21.6%; p = 0.005), as were elevated D-dimer levels (32.3% vs. 15.6%; p = 0.027). Prior cyclosporine use — a surrogate for more refractory disease — was also more common in the HDO group (9.7% vs. 1.2%; p = 0.028). Disease duration did not differ significantly between groups (5.8 vs. 5.4 years; p = 0.305).

Multivariate Analysis Narrows the Field

When entered into a multivariate logistic regression model, only elevated D-dimer retained independent significance. Patients with elevated baseline D-dimer levels had 3.65 times the odds of requiring HDO (OR 3.651; 95% CI 1.208–11.031; p = 0.022). Age, BMI, angioedema, and prior cyclosporine use did not reach independent statistical significance after adjustment.

The authors note, however, that ROC curve analysis revealed limited standalone discriminative ability for D-dimer (AUC = 0.583; p = 0.140), suggesting it functions best as one component of a broader clinical picture rather than a definitive predictive tool.

Mechanistic Context

The association between D-dimer and treatment refractoriness is biologically plausible. Elevated D-dimer reflects activation of the coagulation cascade, which may be driven by eosinophil- and endothelial-derived tissue factor. This activation can enhance vascular permeability and mast cell degranulation — both of which contribute to disease severity and, potentially, resistance to standard-dose biologic therapy. Prior studies, including the SUNRISE study, have similarly documented elevated baseline D-dimer in antihistamine-refractory CSU patients, with levels declining following omalizumab initiation.

Other Parameters: What Didn't Pan Out

Several commonly investigated biomarkers showed no significant association with HDO use. Baseline total IgE levels were comparable between groups, consistent with prior findings from Tuncay et al. and Kocatürk et al.^3,4 CRP elevation was slightly more frequent in HDO patients (25.8% vs. 22.2%) but did not reach significance. Anti-TPO levels, basophil counts, and NLR were similarly distributed across groups.

The finding that IgE levels did not differ between dosing groups likely reflects the heterogeneity of CSU endotypes in the cohort. Total IgE tends to be higher in autoallergic (Type I) CSU and lower in autoimmune (Type IIb) disease, and a mixed population may obscure endotype-specific signals.

Comorbidity burden overall was numerically higher in HDO patients, but did not reach statistical significance. Psychiatric comorbidities appeared more frequently in the HDO group (19.4% vs. 8.3%; p = 0.061) — a trend the authors interpret as potentially reflecting greater psychosocial burden associated with refractory disease rather than a causal factor.

Clinical Takeaways

The findings suggest that while multiple clinical features — older age, higher BMI, angioedema, prior cyclosporine use — may collectively signal more severe and treatment-refractory disease, elevated D-dimer is the only variable independently associated with the need for dose escalation in this cohort. Routine baseline D-dimer assessment may therefore offer additional value in treatment planning for CSU patients being initiated on omalizumab, potentially flagging individuals who may benefit from earlier dose escalation rather than prolonged periods of inadequate disease control.

The authors acknowledge the study's retrospective, single-center design as a limitation and call for prospective multicenter studies to validate these findings before D-dimer can be recommended as a reliable clinical decision-making tool.

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References

1. Casale TB, Gimenez-Arnau AM, Bernstein JA, Holden M, Zuberbier T, Maurer M. Omalizumab for patients with chronic spontaneous urticaria: a narrative review of current status. Dermatol Ther (Heidelb). 2023;13(11):2573-2588. doi:10.1007/s13555-023-01040-9
2. Dizman D, Özay M, Gencebay G, Pasin Ö, Küçük, Ö. Clinical factors associated with high-dose omalizumab use in chronic spontaneous urticaria: a retrospective real-world study. Dermatol Ther. 2026. doi:10.1155/dth/1495031
3. Tuncay G, Damadoglu E, Karakaya G, Fuat Kalyoncu A. Comparison of the characteristics of patients with chronic urticaria receiving standard- or high-dose omalizumab. Eur Ann Allergy Clin Immunol. 2026;58(2):69-76. doi:10.23822/EurAnnACI.1764-1489.380
4. Kocatürk E, Deza G, Kızıltaç K, Giménez-Arnau AM. Omalizumab updosing for better disease control in chronic spontaneous urticaria patients. Int Arch Allergy Immunol. 2018;177(4):360-364. doi:10.1159/000491530