Elevated marker of IgE-mediated mast cell activation predicts omalizumab response in chronic spontaneous urticaria

The finding from the study conducted in CSU treated with omalizumab revealed that 70% of patients who achieved UAS7 response and had controlled diseases had increased pre-treatment sFcɛRI levels (2 ng/mL was used as a cut-off for elevated sFcɛRI). Soluble FcεRI (is) a marker of IgE-mediated mast cell activation. 

"We showed that patients with elevated sFcεRI levels respond better and earlier than those with levels below 2 ng/mL upon omalizumab treatment initiation," the researchers wrote. "This information might help physicians to identify patients who can be expected to show fast benefit from this therapy."

Chronic spontaneous urticaria is a debilitating and common disease characterized by recurrent episodes of angioedema, itchy wheels, or both. The symptoms are due to the activation and degranulation of skin mast cells (MCs). Mechanisms of MC activation in CSU include crosslinking of the high-affinity IgE receptor (FcεRI) by IgG or IgE autoantibodies, but other mechanisms may be relevant.

Omalizumab is an anti-IgE monoclonal antibody that is suggested to be an effective treatment in chronic spontaneous urticaria. However, there has been no identification and characterization of the predictors of fast and good response for omalizumab treatment. Marcus Maurer, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany, and colleagues aimed to evaluate whether soluble FcεRI (sFcεRI), a marker of IgE-mediated mast cell activation, predicts the time of response to omalizumab in CSU.

For this purpose, the researchers obtained sera of 67 CSU patients before omalizumab treatment and analyzed for sFcεRI levels by ELISA. They evaluated treatment response during the first 4 weeks with the rolling UAS7 (rUAS7), urticaria control test (UCT), and urticaria activity score (UAS7).

The study revealed the following findings:

• Elevated pre-treatment sFcɛRI levels were detected in more than 70% of patients with completely controlled disease (UCT = 16) and well-controlled disease (UCT = 12–15) and were significantly associated with disease control (χ2 = 4.94).
• More than half of the patients (14/25) with low levels had poor disease control (UCT < 12).
• Of the patients who achieved complete and marked UAS7 response, respectively, 75% and 63% had elevated baseline sFcɛRI levels.
• Post-treatment UAS7 scores were lower in patients with elevated sFcɛRI levels reaching statistical significance at Week 3.
• Patients with elevated baseline sFcɛRI levels achieved rUAS7 ≤ 6 and = 0 earlier than those with lower levels (Days 9 versus 13 and Days 12 versus 14, respectively).

In the study, the researchers report the first indicator of good and fast response to omalizumab treatment in patients with chronic spontaneous urticaria, sFcεRI.

"The most relevant study finding is that elevated sFcεRI serum levels (>2 ng/mL) before treatment are tied with good and fast response to omalizumab following the first application, concerning disease control and activity," they wrote.

Elevation in sFcεRI serum levels could be a predictor of early and good response to treatment with omalizumab, is the conclusion of the study.

Reference:

Moñino-Romero, S., Kolkhir, P., Ohanyan, T., Szépfalusi, Z., Weller, K., Metz, M., Scheffel, J., Maurer, M., & Altrichter, S. Elevated baseline soluble FcεRI may be linked to early response to omalizumab treatment in chronic spontaneous urticaria. Journal of the European Academy of Dermatology and Venereology. https://doi.org/10.1111/jdv.19485