Omalizumab efficacy in cases of chronic spontaneous urticaria is not explained by the inhibition of sera activity in effector cells

Abstract

Omalizumab (OmAb) is a humanized anti-IgE antibody approved for the treatment of chronic spontaneous urticaria (CSU). OmAb’s mechanism of action is known to include actions on free IgE and on pre-bound IgE. However, OmAb is equally and rapidly effective against autoimmune and non-autoimmune urticaria where IgE involvement is not clear, suggesting the involvement of additional mechanisms of action. In this study, we sought to investigate the ability of OmAb to inhibit mast cell and basophil degranulation induced by sera from CSU patients. For this purpose, we performed a comparison between the in vitro incubation of sera from CSU patients treated with OmAb and the in vivo administration of OmAb in a clinical trial. We found that OmAb added in vitro to sera from CSU patients did not modify the ability of the sera to induce cell degranulation. Similarly, the sera from patients treated with OmAb in the context of the clinical trial who had a good clinical outcome maintained the capacity to activate mast cells and basophils. Thus, we conclude that the beneficial activity of OmAb does not correlate with the ability of patient sera to induce cell degranulation.

Efficacy of Different Dosing Regimens of IgE Targeted Biologic Omalizumab for Chronic Spontaneous Urticaria in Adult and Pediatric Populations: A Meta-Analysis

“… Weekly Itch Score Outcomes with 300 mg dosage of omalizumab [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. ( A ): Mean difference: −4.09 [95% CI: −4.76, −3.42]; Heterogeneity: Tau² = 0.47; Chi² = 79.48, df = 9 ( p < 0.00001); I² = 89%; Test for overall effect: Z = 11.95 ( p < 0.00001).…”

“… Weekly Wheal Score Outcomes with 300 mg dosage of omalizumab [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 26 ]. ( A ): Mean difference: −5.17 [95% CI: −6.90, −3.43]; Heterogeneity: Tau² = 4.97; Chi² = 87.78, df = 8 ( p < 0.00001); I² = 91%; Test for overall effect: Z = 5.82 ( p < 0.00001) ( B ): Standardized mean difference: −1.45 [95% CI: −2.20, −0.69]; Heterogeneity: Tau² = 1.23; Chi² = 191.84, df = 8 ( p < 0.00001); I² = 96%; Test for overall effect: Z = 3.77 ( p = 0.0002).…”

“… Risk of bias assessment of RCTs using the ROB-2 tool [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Weighted summary plot of the overall type of bias encountered in all studies and Traffic light plot of study-by-study bias assessment.…”

Peripheral blood T cell modulation by omalizumab in chronic urticaria patients

“…However, controversial results exist in different studies. Serrano-Candelas et al (30), did not observe any effect of omalizumab in relation with the inhibition of degranulation of mast cells or basophils in chronic urticaria patients' serum either before or during treatment. In contrast, Rodriguez-Trabado et al (31), found a decrease in time in the basophil's activation in a patient treated with omalizumab.…”

Comparative efficacy and safety of the treatment by Omalizumab for chronic idiopathic urticaria in the general population: A systematic review and network meta‐analysis

“…Nine RCTs 14,[30][31][32][33][34][35]39,40 reported adverse events, nine RCTs 14,[30][31][32][33][34][35]39,40 reported the weekly itch severity score, eight studies [30][31][32][33][34][35]39,40 reported the weekly five severity score, nine RCTs 4,14,30,31,33,34,36,39,40 reported weekly urticaria activity scores, and six studies 31,32,34,35,39,40 mentioned the dermatology life quality index. Other characteristics of the included studies are presented in Table 1.…”