The effect of omalizumab treatment on IgE and other immunoglobulin levels in patients with chronic spontaneous urticaria and its association with treatment response

Çildağ, Songül; Şentürk, Taşkın

doi:10.5114/ada.2017.71422

Cited by 21 publications

(8 citation statements)

References 21 publications

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“…The mechanistic reason for the mild effect in neutrophils is unclear and could reflect interference with certain aspects of KIT‐dependent neutrophil differentiation or survival, or indirect modulation of neutrophil tissue distribution as a result of MC suppression. Interestingly, decreases in neutrophil count have also been reported with other approved mAbs that affect MC activity such as the anti‐IgE omalizumab and the anti‐IL4Rα mAb dupilumab 23,58,59 . In addition to its role in hematopoiesis, KIT signaling is important in other processes and has been described to have a role in hair pigmentation and spermatogenesis 31,32,60,61 .…”

Section: Discussionmentioning

confidence: 92%

“…with other approved mAbs that affect MC activity such as the anti-IgE omalizumab and the anti-IL4Rα mAb dupilumab. 23,58,59 In addition to its role in hematopoiesis, KIT signaling is important in other processes and has been described to have a role in hair pigmentation and spermatogenesis. 31,32,60,61 Importantly, the data from preclinical models suggest these effects are fully reversible.…”

Section: Cdx-0159inducesdose-dependent Suppression Of Plasma Tryptase...mentioning

confidence: 99%

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Anti‐KIT monoclonal antibody CDX‐0159 induces profound and durable mast cell suppression in a healthy volunteer study

Alvarado

Maurer

Gedrich

et al. 2022

Allergy

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Background Mast cells (MC) are powerful inflammatory immune sentinel cells that drive numerous allergic, inflammatory, and pruritic disorders when activated. MC‐targeted therapies are approved in several disorders, yet many patients have limited benefit suggesting the need for approaches that more broadly inhibit MC activity. MCs require the KIT receptor and its ligand stem cell factor (SCF) for differentiation, maturation, and survival. Here we describe CDX‐0159, an anti‐KIT monoclonal antibody that potently suppresses MCs in human healthy volunteers. Methods CDX‐0159‐mediated KIT inhibition was tested in vitro using KIT‐expressing immortalized cells and primary human mast cells. CDX‐0159 safety and pharmacokinetics were evaluated in a 13‐week good laboratory practice (GLP)‐compliant cynomolgus macaque study. A single ascending dose (0.3, 1, 3, and 9 mg/kg), double‐blinded placebo‐controlled phase 1a human healthy volunteer study (n = 32) was conducted to evaluate the safety, pharmacokinetics, and pharmacodynamics of CDX‐0159. Results CDX‐0159 inhibits SCF‐dependent KIT activation in vitro. Fc modifications in CDX‐0159 led to elimination of effector function and reduced serum clearance. In cynomolgus macaques, multiple high doses were safely administered without a significant impact on hematology, a potential concern for KIT inhibitors. A single dose of CDX‐0159 in healthy human subjects was generally well tolerated and demonstrated long antibody exposure. Importantly, CDX‐0159 led to dose‐dependent, profound suppression of plasma tryptase, a MC‐specific protease associated with tissue MC burden, indicative of systemic MC suppression or ablation. Conclusion CDX‐0159 administration leads to systemic mast cell ablation and may represent a safe and novel approach to treat mast cell‐driven disorders.

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Section: Discussionmentioning

confidence: 92%

Section: Cdx-0159inducesdose-dependent Suppression Of Plasma Tryptase...mentioning

confidence: 99%

Anti‐KIT monoclonal antibody CDX‐0159 induces profound and durable mast cell suppression in a healthy volunteer study

Alvarado

Maurer

Gedrich

et al. 2022

Allergy

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“…16 Moreover, Çilda g et al found a decrease in the number of neutrophils in urticaria patients receiving omalizumab. 17 SII is one of the newly prognostic biomarker based on platelets, neutrophils, and lymphocytes. The clinical observation studies indicate that SII is a powerful tool for predicting survival outcomes and appears to be a simple and inexpensive tool in the prediction of the progression of a diverse number of diseases.…”

Section: Discussionmentioning

confidence: 99%

New markers to predict the response to omalizumab in chronic spontaneous urticaria

Coşansu

Kara

Yaldız

et al. 2022

Dermatologic Therapy

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Omalizumab has high treatment efficacy in patients with chronic spontaneous urticaria (CSU) who do not respond to high doses of antihistamines. Systemic immuneinflammation index (SII) and systemic inflammation response index (SIRI) were described as novel inflammatory and prognostic biomarkers. The present study aimed to evaluate the effectiveness of SII and SIRI in patients with CSU who receive omalizumab therapy. A total of 124 patients with severe urticaria who had an urticaria activity score over 7 days (UAS-7) ≥28 were included in the study. UAS-7, Creactive protein (CRP), SII, and SIRI values were recorded before and after omalizumab treatment. Patients with UAS-7 ≤6 at week 12 and/or week 24 of omalizumab treatment were considered responders. Three months after omalizumab treatment, significant decreases were observed in SII, SIRI, CRP, and UAS-7 compared to pre-treatment values (p = 0.003, p < 0.001, p = 0.006, and p < 0.001, respectively). At the third and sixth months of treatment, baseline SII and SIRI levels of the omalizumab responder group were significantly higher than the non-responder group (p < 0.001). However, there was no difference in baseline CRP and UAS-7 levels between responders and non-responders (p > 0.05). After adjusting for confounding factors, only pre-treatment SII (OR: 1.002, 95% CI: 1.000-1.004, p = 0.036) and SIRI (OR: 4.334, 95% CI: 1.751-10.726, p = 0.002) values were independently associated with response to omalizumab at 3 months in multivariate regression analysis. SII and SIRI could be effectively used to predict the response to omalizumab therapy. More comprehensive studies are needed to validate and elaborate on this relationship.

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“…Among other biologics that inhibit Th2 pathways, only omalizumab was associated with alopecia in this study, probably due to the increased total IgE levels after omalizumab use. Omalizumab, an anti-IgE agent, is known to decrease free IgE levels and increase total IgE levels [ 43 , 44 ]. Our disproportionality analysis revealed that, unlike omalizumab, dupilumab induced both hair growth and hair loss.…”

Section: Discussionmentioning

confidence: 99%

Short communication: Comments on hair disorders associated with dupilumab based on VigiBase

Park

Byun

et al. 2022

PLoS ONE

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Background Dupilumab is a human antibody that blocks the signaling of both interleukin-4 and interleukin-13 receptors. It has been approved for the treatment of moderate-to-severe atopic dermatitis. However, several case reports have reported conflicting effects of dupilumab on alopecia. Objectives This study aimed to examine dupilumab-related hair disorders using the large real-world database, VigiBase. Methods All individual case safety reports associated with dupilumab in the Uppsala Monitoring Center VigiBase until December 29, 2019, were analyzed. Hair disorder-related terms were defined in High Level Terms with “alopecias,” “pilar disorders NEC (not elsewhere classified),” and “hypertrichoses,” using the Medical Dictionary for Regulatory Activities Hierarchy. Hair disorder reports associated with dupilumab and other biologics that inhibit the Th2 axis (omalizumab, mepolizumab, reslizumab, and benralizumab) were analyzed to determine their association with hair disorders. Disproportionality analysis was performed based on the proportional reporting ratio, reporting odds ratio, and information components. Results Among the 20,548 total dupilumab adverse event (AE) reports, hair disorders were reported in 462 dupilumab cases (2.2%), most of which reported hair loss, and only eight cases reported an increase in hair growth. The paradoxical trend in hair loss and growth after dupilumab use was confirmed using a disproportionality analysis. Among the other investigated biologics on Th2 immunity, only omalizumab was associated with hair loss. Additionally, hair disorders after dupilumab treatment were more frequently reported in women than in men. The proportion of hair disorder cases was high in Europe, accounting for 20.8% of hair disorder reports, whereas only 9.7% of all dupilumab-related AEs were reported in Europe. In conclusion, our analysis using a large real-world database confirmed that dupilumab is associated with hair disorders.

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The effect of omalizumab treatment on IgE and other immunoglobulin levels in patients with chronic spontaneous urticaria and its association with treatment response

Cited by 21 publications

References 21 publications

Anti‐KIT monoclonal antibody CDX‐0159 induces profound and durable mast cell suppression in a healthy volunteer study

Anti‐KIT monoclonal antibody CDX‐0159 induces profound and durable mast cell suppression in a healthy volunteer study

New markers to predict the response to omalizumab in chronic spontaneous urticaria

Short communication: Comments on hair disorders associated with dupilumab based on VigiBase

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