Omalizumab Research Articles

Hematopoietic stem cell transplantation in patient with DOCK8 deficiency: Ukrainian experience

Dedicator of Cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency that exemplifies the broad clinical features of primary immunodeficiencies (PIDs), extending beyond recurrent infections including atopy, autoimmunity, and cancer. Purpose - to describe the natural course of hyper-IgE syndrome (HIES) disease in an 8-year-old boy and his path to diagnosis, as well as our first local history of conservative treatment for 6 months. In particular, we describe the effectiveness of omalizumab, and the application of allogeneic hematopoietic stem cell transplantation with follow-up. Clinical case. The 8-year-old boy presented with severe eczema and an involvement of the whole surface of the body. Infectious syndrome manifested from the age of 4 months in a form of recurrent respiratory infections. Over the next few years, the child suffered from life-threatening infections with high serum IgE (>3000 IU/ml). The examination revealed a cushingoid constitution, flat-valgus feet, and dysmorphic features. Therefore, HIES was suspected. Genetic studies have confirmed the diagnosis by detecting a pathogenic homozygous mutation in the DOCK8 gene (Deletion Exons 2-46). We decided to use a humanized monoclonal anti-IgE antibody (off-label) to control the skin syndrome rather than systemic steroids. A significant improvement in skin condition, a decrease in eosinophils, and IgE were observed. Allogeneic stem cell transplantation of hematopoietic cells (HSCT) derived from peripheral blood of an human leukocyte antigen (HLA) - identical sibling donor was performed. The donor had a pathogenic mutation identical to the recipient in the DOCK8 gene but in a heterozygous state. Our data and treatment approach may be clinically useful as a diagnostic and treatment approach to HIES. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies No conflict of interests was declared by the authors.

Combination of omalizumab with allergen immunotherapy versus immunotherapy alone for allergic diseases: A meta-analysis of randomized controlled trials.

Allergen immunotherapy (AIT)-associated adverse events (AEs) limit its usage in the management of allergic diseases. The monoclonal anti-IgE antibody (omalizumab) and AIT have complementary actions. However, no consensus has been reached on whether their combination could exert superior efficacy and safety. To evaluate whether the combination of AIT with omalizumab is superior to AIT alone in treating allergic diseases. The MEDLINE/PubMed, Embase, Scopus and Cochrane Library databases were searched to identify randomized control trials (RCTs) reporting the outcomes of omalizumab combined with AIT (omalizumab + AIT) versus AIT alone. A random-effect model was established to estimate outcomes with a 95% confidence interval (CI). A total of 11 eligible RCTs (involving 901 patients) were screened out for the meta-analysis. According to a pooled analysis, omalizumab + AIT significantly increased the number of patients achieving the target maintenance dose (TMD) and sustained unresponsiveness (SU) to allergens (odds ratio [OR]=2.43; 95% CI: 1.33-4.44; p=0.004; I2=35%, and OR=6.77; 95% CI: 2.10-21.80; p=0.001; I2=36%, respectively). Similarly, individuals receiving the combination therapy reported significantly fewer episodes of severe systemic AEs than AIT alone (OR=0.32; 95% CI: 0.18-0.59; p=0.0003; I2=0%). Meanwhile, the improvements in symptom severity score (mean difference [MD]=-0.26), rescue medication daily means score (MD=-0.14), and number of patients consuming epinephrine in AIT (OR=0.20) were all more evident than those in AIT alone. Omalizumab + AIT can significantly enhance the efficacy and safety of AIT by increasing TMD and SU to allergens, while decreasing severe systemic AEs.

Is anti-IgE therapy effective in preventing magnesium and selenium loss in bones of mice with chronic allergic asthma?

Objective: Chronic allergic asthma (CA) is a respiratory disease that affects millions of people worldwide. While there is evidence linking airway hyperresponsiveness and asthma to factors related to bone metabolism, the impact of asthma on bone health is not well understood. Therefore, to explore whether: (i) CA causes meaningful changes in bone magnesium (Mg) and selenium (Se) levels, and if any, (ii) anti-IgE (anti-immunoglobulin E) treatment has a protective effect against these changes.
 Methods: In present study used tibia bones from a previous study on CA in mice. A murine model was used to generate CA. Thirty-two BALB/c male mice were randomly divided into four equal sized groups (eight mice/group): control group (intact), CA (treated with saline (0.9% NaCl), CA+L-AIgE (100 μg of anti-IgE), CA+H-AIgE (200 μg of anti-IgE). After immunization, saline was administered by inhalation three times a week. Anti-IgE applications were performed intraperitoneally for a total of 8 weeks in five sessions with 15-day intervals. Bone Mg and Se levels are determined by inductively coupled plasma mass spectrometry (ICP-MS), which is used to determine the elemental composition of various samples.
 Results: Mg levels of CA and CA+L-AIgE groups were significantly decreased compared to the control (P

Elevated baseline soluble FcεRI may be linked to early response to omalizumab treatment in chronic spontaneous urticaria.

Omalizumab, an anti-IgE monoclonal antibody, is an effective treatment in chronic spontaneous urticaria (CSU). Predictors of fast and good response for omalizumab treatment have not yet been identified and characterized. To evaluate whether soluble FcεRI (sFcεRI), a marker of IgE-mediated mast cell activation, predicts the time of response to omalizumab in CSU. Sera of 67 CSU patients were obtained before omalizumab treatment and analysed for sFcεRI levels by ELISA (2 ng/mL was used as cut-off for elevated sFcɛRI). Treatment response during the first 4 weeks was assessed with the urticaria activity score (UAS7), urticaria control test (UCT) and the rolling UAS7 (rUAS7). 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, p < 0.05). 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 (p < 0.05). Patients with elevated baseline sFcɛRI levels achieved rUAS7 ≤ 6 and = 0 earlier than those with lower levels (Days 9 vs. 13 and Days 12 vs. 14, respectively). Elevated sFcεRI serum levels predict early and good response to treatment with omalizumab, which may help to better design treatment options for CSU patients.

Comprehensive Assessment of Pharmacokinetics, Pharmacodynamics, and Tolerability of Ligelizumab in Healthy Volunteers and Patients with Chronic Spontaneous Urticaria to Optimize Its Subcutaneous Delivery System.

Ligelizumab is a highly potent, humanized IgG1, anti-IgE monoclonal antibody. To explore its optimal subcutaneous delivery, the pharmacokinetics (PK), pharmacodynamics (PD), and tolerability of ligelizumab from two Phase 1 studies in healthy volunteers (HVs) and four Phase 2 and 3 studies in patients with chronic spontaneous urticaria (CSU) were assessed. Using different injection volumes or durations of a liquid-in-vial (LIVI) formulation or different formulations (LIVI vs. prefilled syringe (PFS)), single-dose ligelizumab showed comparable PK exposure in HVs. Steady-state exposure of ligelizumab was also comparable between LIVI and PFS following multiple dosing in CSU patients. The total IgE level (a PD marker) and tolerability were similar between the two formulations in both HVs and patients. Furthermore, the PK, total IgE, and tolerability were comparable for PFS administered either by patients or healthcare providers (HCPs). Collective evidence demonstrated that the injection duration or volume, formulation, or administrator had no apparent impact on the PK, PD, and tolerability of ligelizumab, supporting no clinically relevant difference between LIVI and PFS, and that PFS can be administered by patients or HCPs. This report provides a comprehensive assessment based on data of multiple clinical endpoints from both HVs and patients to inform formulation development and commercial use of a monoclonal antibody.

Omalizumab Drug Survival in Chronic Urticaria: A Retrospective Multicentric French Study

Omalizumab (OMA) dramatically improves disease control and quality of life in patients with chronic urticaria (CU). We aimed to evaluate the discontinuation patterns of OMA and their determinants in a cohort of French patients with CU. We conducted a retrospective multicenter study in 9 French tertiary referral hospitals. All patients diagnosed with either spontaneous (CSU) and/or inducible (CIndU) CU who received at least 1 injection of OMA between 2009 and 2021 were included. We analyzed OMA drug survival and investigated possible determinants using Kaplan-Meier curves and log-rank tests. A total of 878 patients were included in this study; 48.8% had CSU, 10.1% CIndU, and 41.1% a combination of both. OMA was discontinued in 408 patients, but the drug was later reintroduced in 50% of them. The main reason for discontinuing treatment was the achievement of a well-controlled disease in 50% of patients. Half of the patients were still being treated with OMA 2.4 years after the initiation of treatment. Drug survival was shorter in patients with CIndU and in those with an autoimmune background. In atopic patients, OMA was discontinued earlier in patients achieving a well-controlled disease. A longer OMA drug survival was observed in patients with a longer disease duration at initiation. In French patients with CU, the drug survival of OMA appears to be longer than that observed in previous studies conducted elsewhere, highlighting discrepancies in prescription and reimbursement possibilities. Further studies are warranted to develop customized OMA treatment schemes based on individual patterns.

The challenge of omalizumab refractory chronic spontaneous urticaria and the relevance of suspecting Schnitzler syndrome without monoclonal gammopathy

Introduction: Schnitzler syndrome (SchS) is a rare autoinflammatory syndrome characterized by chronic urticaria and monoclonal gammopathy (MG). Clinical cases without monoclonal gammopathy have been recorded. Clinical Case: We report on the case of a 43-year-old female with chronic spontaneous urticaria refractory to omalizumab (OMZ) despite a dosage increase (600 mg/4 weeks). Additionally, she developed asthenia and episodes of arthralgias and fever predominantly in the evening. Laboratory re-evaluation revealed elevated inflammatory parameters and skin biopsy showed neutrophilic infiltration. Although MG was absent, SchS was the most likely diagnosis, as other differential diagnoses were excluded. Treatment was started with anakinra, with complete resolution of symptoms. Conclusion: We highlight the importance of specialized urticaria clinics and of reassessing the diagnosis in patients with refractory chronic urticaria. An autoinflammatory disease, such as SchS, could be the diagnosis, even without the presence of monoclonal gammopathy.

Long-Term Omalizumab Therapy in Patients with Chronic Spontaneous Urticaria: Does it Increase the Risk of COVID-19?

Based on the existing literature, omalizumab (OMZ) is considered a safe treatment modality in chronic spontaneous urticaria (CSU) during the coronavirus disease 19 (COVID-19) era. The aim of this study is to evaluate the effects of OMZ on CSU patients regarding COVID-19 infection. In this retrospective study, files of CSU patients using OMZ during the COVID-19 pandemic were reviewed in terms of demographic features, medical history including COVID-19 vaccination status, clinical characteristics, pretreatment laboratory parameters, duration, and dosing regimen of OMZ treatment. Patients with a history of COVID-19 infection while on OMZ therapy and patients without COVID-19 history were compared with respect to these parameters. The urticaria activations following COVID-19 infection or vaccination were also recorded. Sixty-eight patients with CSU (female:male ratio = 1.8:1; mean age = 47.2 ± 15.1 years) continued to receive OMZ treatment. The median duration of OMZ treatment was 12 months (range: 6-60). Twelve patients (17.6%) were diagnosed with COVID-19 showing no exacerbation in urticaria. The duration of OMZ treatment was significantly higher in the group with COVID-19 infection history compared to patients with no history of COVID-19 (P = 0.01). Among 51 patients (75%) vaccinated against COVID-19, urticaria activation occurred in 4 patients without any recurrence following booster vaccinations. Considering the likelihood of increased COVID-19 infection risk in the setting of long-term OMZ in CSU patients, the duration of OMZ therapy might be kept at a minimum, or a temporary interruption of the treatment period might be preferred, particularly in high-risk patients regarding COVID-19.

Omalizumab in the treatment of various forms of chronic urticaria

BACKGROUND: Chronic urticaria is a skin disease characterized by the appearance of itchy weals and/or angioedema for 6 or more weeks. Chronic urticaria is subdivided into chronic spontaneous urticaria, which occurs due to an unknown cause, and chronic inducible urticaria, which occurs as a result of exposure to various physical factors (water, cold, heat, pressure, mechanical irritation), can occur simultaneously or independently of each other. Omalizumab, anti-IgE monoclonal antibody, is approved for the treatment of patients with chronic spontaneous urticaria and is the second choice in cases of resistance to antihistamine treatment. In patients with a combination of chronic spontaneous urticaria and chronic inducible urticaria, the effectiveness of treatment with omalizumab has been little studied.&#x0D; AIM: compare the effectiveness of omalizumab treatment in patients with chronic spontaneous urticaria and patients with a combination of chronic spontaneous and chronic induced urticaria.&#x0D; MATERIALS AND METHODS: Under supervision there were 30 patients with chronic spontaneous urticaria and combined chronic spontaneous and inducible urticaria (15 patients in each group). Evaluation of the effectiveness of treatment was carried out according to the results of the questionnaires DLQI (dermatological index of quality of life), CU-Q2oL (questionnaire for quality of life in chronic urticaria), UCT (urticaria control test), UAS (urticaria activity scale), HADS (Hospital Anxiety and Depression Scale) and provocation tests in dynamics before and during treatment.&#x0D; RESULTS: All patients received omalizumab 300 mg subcutaneously once a month for 6 to 12 months. After the first injection of omalizumab, we noted a decrease in the severity of urticaria, an increase in the level of disease control and quality of life when comparing parameters before and during treatment in more than 90% of patients. Improved performance remained at this level throughout all subsequent months of treatment.&#x0D; CONCLUSION: Omalizumab is equally effective in patients with an isolated form of chronic spontaneous urticaria and in patients with a combined form of chronic spontaneous and inducible urticaria. The use of omalizumab allows you to control the symptoms of chronic spontaneous and inducible urticaria, even with prolonged use.

Characteristics of immune response profile in patients with immediate allergic and autoimmune urticarial reactions induced by SARS-CoV-2 vaccines

Severe allergic reactions following SARS-COV-2 vaccination are generally rare, but the reactions are increasingly reported. Some patients may develop prolonged urticarial reactions following SARS-COV-2 vaccination. Herein, we investigated the risk factors and immune mechanisms for patients with SARS-COV-2 vaccines-induced immediate allergy and chronic urticaria (CU). We prospectively recruited and analyzed 129 patients with SARS-COV-2 vaccine–induced immediate allergic and urticarial reactions as well as 115 SARS-COV-2 vaccines–tolerant individuals from multiple medical centers during 2021–2022. The clinical manifestations included acute urticaria, anaphylaxis, and delayed to chronic urticaria developed after SARS-COV-2 vaccinations. The serum levels of histamine, IL-2, IL-4, IL-6, IL-8, IL-17 A, TARC, and PARC were significantly elevated in allergic patients comparing to tolerant subjects (P-values = 4.5 × 10−5–0.039). Ex vivo basophil revealed that basophils from allergic patients could be significantly activated by SARS-COV-2 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P-values from 3.5 × 10−4 to 0.043). Further BAT study stimulated by patients’ autoserum showed positive in 81.3% of patients with CU induced by SARS-COV-2 vaccination (P = 4.2 × 10−13), and the reactions could be attenuated by anti-IgE antibody. Autoantibodies screening also identified the significantly increased of IgE-anti–IL-24, IgG-anti–FcεRI, IgG-anti–thyroid peroxidase (TPO), and IgG-anti-thyroid–related proteins in SARS-COV-2 vaccines-induced CU patients comparing to SARS-COV-2 vaccines-tolerant controls (P-values = 4.6 × 10−10–0.048). Some patients with SARS-COV-2 vaccines-induced recalcitrant CU patients could be successfully treated with anti-IgE therapy. In conclusion, our results revealed that multiple vaccine components, inflammatory cytokines, and autoreactive IgG/IgE antibodies contribute to SARS-COV-2 vaccine–induced immediate allergic and autoimmune urticarial reactions.

Cytokine-targeted treatment in alopecia areata - new possibilities?

Alopecia areata is a form of non-scarring hair loss characterised by a recurrent and difficult-to-treat course. The aetiology of this disease is still incompletely understood. However, multiple immunological pathways and an abnormal cytokine profile in patients with alopecia areata have been described. There are many therapeutic options for patients with alopecia areata, including topical, intralesional or systemic corticosteroids, contact immunotherapy, phototherapy and non-corticosteroid immunosuppressive drugs such as cyclosporine, methotrexate or azathioprine. However, these treatments have limited efficacy and may be associated with side effects. In addition, Janus kinase inhibitors have been shown to cause metabolic disorders. Therefore, their use in patients with alopecia areata may be limited. Other cytokine-targeted therapies have been shown to be effective in alopecia areata, such as apremilast (a phosphodiesterase 4 inhibitor), ustekinumab (a human immunoglobulin (Ig) G1 kappa monoclonal antibody directed against interleukin 12 and 23), abatacept (a soluble fusion protein which links the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 to the modified Fc portion of human immunoglobulin G1), secukinumab (an IL-17A antagonist) and dupilumab (a monoclonal antibody that blocks interleukin 4 and interleukin 13). TNF inhibitors (such as infliximab, adalimumab and etanercept) have been described to be ineffective in alopecia areata. In addition, disease exacerbation after TNF therapy has been reported. Alefacept (an immunosuppressive dimeric fusion protein that consists of the extracellular CD2-binding part of human leukocyte function antigen-3 fused to the Fc part of human IgG1) and efalizumab (anti-CD11a monoclonal antibody) have not shown efficacy in alopecia areata. There are also isolated reports of alopecia areata after therapy with omalizumab (recombinant humanised monoclonal antibody anti-IgE), ixekizumab (inhibitor of IL-17A) and brodalumab (inhibitor of IL-17R).

Dupilumab as Adjunct Treatment for Persistent Food Allergy in Adulthood

Atopic disease affects both immunocompetent and immunodeficient patients. Known risk factors for atopic disease, such as atopic dermatitis (AD) and IgE mediated food allergy, include impaired skin integrity, Th2 predominance, and altered T-regulatory activity. Food allergies in particular can be life-threatening and there is no known cure, although immunomodulatory (anti IL-4Rα/IL-13, anti IL-5, and anti IgE) trials for food allergy are underway. The allergen-specific IgE levels and skin prick tests of atopic dermatitis patients often decrease while on dupilumab (anti IL-4Rα/IL-13) therapy but the question remains: does dupilumab improve or eliminate food allergy? One case report has reported success with dupilumab in an adult woman. Here we describe the de-labeling of several allergenic foods in an adult patient being treated for AD with dupilumab.A 29-year-old man presented to our allergy clinic with a history of severe AD and multiple food allergies. His eczema had been recalcitrant to high-dose topical steroids, BB-UVB phototherapy, cyclosporine, methotrexate, and both intramuscular and intralesional Kenalog (ILK). He finally improved on weekly dupilumab dosing and did not have adverse effects from dupilumab therapy. His food allergies posed significant morbidity with multiple reactions requiring epinephrine as well as ongoing anxiety regarding cross-contact. His history is notable for childhood reactions to peanut, tree nuts, fish, and shellfish, with concordantly elevated skin prick and specific IgE levels. After dupilumab therapy, these reactions decreased, leading to a risk/benefit discussion and agreement to perform physician-guided oral food challenges in an effort to broaden his diet (Figure 1). The majority of challenges were passed and the patient has maintained those foods in his diet (Figure 2). In addition, the patient reports substantial improvement in his anxiety at work as well as in social interactions. In this case, dupilumab as an immodulatory agent for AD offered the additional benefit of decreasing morbidity from food allergies. Given the persistence of food allergy, further research into adjunctive therapeutic options is vital to improving patient quality of life. Unlike other therapies like JAKinhibitors and systemic steroids used for atopic dermatitis, anti-IL-4Rα/IL-13 therapy is not immunosuppressive and has a favorable side-effect profile for patients. [Display omitted] [Display omitted]

Avapritinib for the Treatment of Indolent Systemic Mastocytosis

Indolent systemic mastocytosis (ISM) is a disorder characterized by an accumulation of mast cells in subdermal tissue that leads to exaggerated immune response after release of mast cells mediators. Routinely administered treatments include H1 and H2 receptor antagonists, mast cell stabilizers, corticosteroids, and more recently anti-IgE antibody therapies. Our case presentation explores the treatment of indolent mastocytosis with avapritinib, an antineoplastic, after routine treatment options failed.A 64-year-old female with history of obesity presented to a community-based Allergy/Immunology clinic with chief complaints of recurrent throat tightness, fatigue, headaches, brain fog. She was found to have high tryptase levels which remained persistently elevated from 46 to 55 (include units) over 13-month span. Physical exam was grossly unremarkable.Bone marrow biopsy showed mast cell aggregates highly suspicious for ISM. PCR for KIT (D816V) mutation was positive. Initial treatment included fexofenadine 180 mg and famotidine 20 mg both twice daily. Overall, she had less frequent episode of throat tightness over 9 months, but itchiness, fatigue, brain fog persisted. Monthlyomalizumab 300 mg was added on but was eventually discontinued to lack of benefit. She was referred to a tertiary center where avapritinib 25 mg daily was started. Four months after initiation, occurrences of throat tightness, stomach cramps, and vomiting resolved, and came off all other therapies for mastocytosis. Eight months after avapritinib initiation tryptase had decreased to 19.Avapritinib is a selective kinase inhibitor used to avoid resistance in patients undergoing chemotherapy with indications in those with advanced systemic mastocytosis and neoplastic complications. The mechanism of action of avapritinib includes inhibition of KIT and PDGFRA mutations. Treatment in our patient resulted in the successful symptomatic treatment of indolent systemic mastocytosis targeting KIT (D816V). This case demonstrates a new treatment which may improve the quality of life of individuals with ISM.

A mechanism for the elimination of IgE plasma cells

Abstract The proper regulation of IgE production safeguards against allergic disease, highlighting the importance of mechanisms that restrict IgE plasma cell (PC) survival. IgE PCs have unusually high surface B cell receptor (BCR) expression, yet the functional consequences of ligating this receptor are unknown. Here, we found that BCR ligation induced BCR signaling in IgE PCs followed by their elimination. In cell culture, exposure of IgE PCs to cognate antigen or anti-BCR antibodies induced apoptosis. IgE PC depletion correlated with the affinity, avidity, amount, and duration of antigen exposure and required the BCR signalosome components Syk, BLNK, and PLCγ2. In mice with a PC-specific impairment of BCR signaling, the abundance of IgE PCs was selectively increased. Conversely, BCR ligation by injection of cognate antigen or anti-IgE depleted IgE PCs. These findings establish a mechanism for the elimination of IgE PCs through BCR ligation. This has important implications for allergen tolerance and immunotherapy as well as anti-IgE monoclonal antibody treatments. This research was supported by the National Institute of Allergy and Infections Diseases of the National Institutes of Health under Award Number R01AI130470; the Program for Breakthrough Biomedical Research, which is partially funded by the Sandler Foundation; the Sandler Asthma Basic Research Center; and the Cardiovascular Research Institute at the University of California, San Francisco. C.D.C.A. was a Pew Scholar in the Biomedical Sciences, supported by The Pew Charitable Trusts. A.K.W-V was supported by a Doctoral Foreign Study Award from the Canadian Institute of Health Research, funding reference number DFD-170769. D.M.T. and M.J.R. were funded by National Health and Medical Research Council (NHMRC) Australia by an Investigator Award (APP1175411) and Ideas Grant (APP1185294), respectively. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Efficacy of two-year anti-IgE therapy in patients with severe allergic bronchial asthma in Sverdlovsk region

Introduction. The study of omalizumab efficacy in patients with severe bronchial asthma (SA) in randomized clinical trials is limited to 52 weeks. In real clinical practice, patients can receive the drug for much longer.Aim. Evaluate the one-year and two-year efficacy of omalizumab in patients with SA in Sverdlovsk region.Material and methods. The study included patients (n = 54) with allergic and mixed SA from the registry of Sverdlovsk region. Omalizumab efficacy was assessed over 12 and 24 months of therapy by dynamics of asthma exacerbations frequency, the use of health care resources, the need for short-acting beta-agonists (SABA) and systemic glucocorticosteroids (SGCS), the level of asthma control according to ACT, and the quality of life according to AQLQ, FEV1 levels and peripheral blood eosinophils.Results. During 12 months of omalizumab therapy, the reduction in asthma exacerbation rate was 63.7% (from 2.01 ± 1.51 per patient per year to 0.73 ± 1.03) (p &lt; 0.001), which was accompanied by a decrease in emergency calls and hospitalizations rates by 92.4 and 84.1%, respectively (p &lt; 0.001). Improved asthma control (by ACT) from 9 (Q1-Q3: 7–13) to 20 points (Q1-Q3: 16–23); the proportion of patients with uncontrolled SA decreased from 97.4 to 48.7% (p &lt; 0.001). The need for SABA decreased to 92.9% (p &lt; 0.001). The proportion of patients on SGCS decreased from 60.5% to 15.8% (p &lt; 0.001). The quality of life (AQLQ) significantly improved, FEV1 increased (p &lt; 0.001), the number of eosinophils in peripheral blood decreased (p = 0.015). By the end of the second year of therapy, the trend of improvement in indicators of efficacy continued.Conclusions. During 1 year of therapy with omalizumab, patients with allergic SA experienced a significant decrease in the number of exacerbations and use of health care resources, improved quality of life and asthma control, reduced need for SABA and SGCS, and improved respiratory function. In patients treated with omalizumab for 2 years, there was a further improvement or stabilization of efficacy indicators.

Chronic Urticaria Treatment with Omalizumab-Verification of NLR, PLR, SIRI and SII as Biomarkers and Predictors of Treatment Efficacy.

Biomarkers that are able to predict the response to omalizumab (OMA) in chronic spontaneous urticaria (CSU) are highly valued. The aim of our study was to evaluate the UAS7 (urticaria activity score assessed for 7 days), DLQI (dermatology life quality index), SII (systemic immune-inflammation index), SIRI (systemic inflammation response index), PLR (platelet/lymphocyte ratio) and NLR (neutrophil/lymphocyte ratio) in a group of 46 CSU a patients treated for 24 weeks with OMA (300 mg every 4 weeks). There were no statistically significant differences observed at the start nor at the end of the treatment between the two groups (responders vs. non-responders) and SII, SIRI, PLR and NLR. However, a statistically significant correlation was observed between severity of urticaria expressed in UAS7 scores and the quality of life (evaluated by DLQI). Furthermore, at week 24, both groups demonstrated significant improvement in quality of life. Our single center study did not confirm the usefulness of SII, SIRI, NLR or PLR as predictors of the response to OMA in CSU. However, it is of importance that even patients who did not respond to the treatment presented a significant improvement in quality of life. Additionally, we also observed that the efficacy of treatment was unchanged amongst patients who underwent a second series of treatment in cases of relapse.

Research progress of omalizumab in the treatment of bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune blistering disease associated with anti-BP180 and anti-BP230 antibodies. The pathogenic action mechanism of immunoglobulin E (IgE) antibodies in BP has been studied since the 1970s, and IgE antibodies have gradually been confirmed as being important in BP; therefore, anti-IgE therapy may be a new option for the treatment of BP. Omalizumab, as an IgE monoclonal antibody, has been increasingly used clinically to treat BP in recent years. Here, we collected 35 papers investigating omalizumab for BP treatment in a total of 83 patients, and the vast majority of patients showed varying degrees of improvement after treatment, except for a small number of patients with poor clinical outcomes. The patients were then divided into three groups according to dosing frequency and number of doses. Statistical analysis indicated that dosing frequency had little effect on clinical efficacy. While the groups with different numbers of doses were evaluated, the results concluded that clinical efficacy was affected by the number of doses, but there was no positive correlation between the number of doses and clinical efficacy.

Remibrutinib inhibits hives effector cells stimulated by serum from chronic urticaria patients independently of FcεR1 expression level and omalizumab clinical response.

Despite advances in the treatment of chronic urticaria, in a significant percentage of the patients symptoms are not fully controlled with conventional approaches. New strategies under development include blocking intracellular mediators of mast cell and basophil activation. We aim to investigate the effects of the Bruton's tyrosine kinase (BTK) inhibitor remibrutinib on human blood basophils and CD34+ -derived mast cells activation induced by serum obtained from chronic urticaria patients. Twenty-two patients with chronic spontaneous urticaria (mean age 52years, 27% women) and 22 patients with chronic inducible urticaria (46years, 27% women) were included in the study together with a sex-matched control group. Patients were classified as responders or non-responders to anti-IgE therapy on the basis of their clinical data, FcεR1a expression on blood basophils and total IgE levels. Changes on CD63 expression-as an activation marker-, were used to evaluate in vitro the response of basophils and mast cells to serum exposure and the inhibitory effects of remibrutinib. Remibrutinib inhibits degranulation induced by IgE cross-linking in mast cells and basophils and also the activation triggered by factors present in the sera of spontaneous and inducible chronic urticaria patients. Patient's serum induces a greater degranulation of effector cells than controls. Activation of mast cells and basophils by patient sera and remibrutinib effects were not related to omalizumab responsiveness. Remibrutinib inhibits activation of human basophils and mast cells induced in vitro by exposure to the serum of chronic urticaria patients independently of their response to omalizumab.

B cell receptor ligation induces IgE plasma cell elimination.

The proper regulation of IgE production safeguards against allergic disease, highlighting the importance of mechanisms that restrict IgE plasma cell (PC) survival. IgE PCs have unusually high surface B cell receptor (BCR) expression, yet the functional consequences of ligating this receptor are unknown. Here, we found that BCR ligation induced BCR signaling in IgE PCs followed by their elimination. In cell culture, exposure of IgE PCs to cognate antigen or anti-BCR antibodies induced apoptosis. IgE PC depletion correlated with the affinity, avidity, amount, and duration of antigen exposure and required the BCR signalosome components Syk, BLNK, and PLCγ2. In mice with a PC-specific impairment of BCR signaling, the abundance of IgE PCs was selectively increased. Conversely, BCR ligation by injection of cognate antigen or anti-IgE depleted IgE PCs. These findings establish a mechanism for the elimination of IgE PCs through BCR ligation. This has important implications for allergen tolerance and immunotherapy as well as anti-IgE monoclonal antibody treatments.

The Identification of Potential Immunogenic Antigens in Particular Active Developmental Stages of the Rice Weevil (Sitophilus oryzae).

The rice weevil (Sitophilus oryzae) originates from subtropical and tropical areas of Asia and Africa, but it also appears on other continents, mostly as a result of trade in rice. It may occur in grain fields as well as in storage facilities, and cause allergenic reactions. The aim of this study was to identify the potential antigens in all developmental stages of S. oryzae, which may cause an allergic response in humans. Sera of 30 patients were tested for the presence of IgE antibodies to antigens from three life stages of the rice weevil. To identify protein fractions containing potential allergens, proteins collected from larvae, pupae, and adults separated by sex of S. oryzae were fractionated by SDS-PAGE. Then, they were probed with anti-human, anti-IgE monoclonal antibodies, fractionated by SDS-PAGE and detected by Western blotting. In total, 26 protein fractions of males and 22 fractions of other life stages of S. oryzae (larvae, pupae, and females) positively reacted with the examined sera. The conducted study showed that S. oryzae may be a source of many antigens which may cause the potential allergic reactions in humans.