-
Immunology Letters Nov 2020Omalizumab therapy was found to be safe and effective as an add-on therapy for patients with poorly controlled severe asthma. Although several studies over the last... (Observational Study)
Observational Study
BACKGROUND
Omalizumab therapy was found to be safe and effective as an add-on therapy for patients with poorly controlled severe asthma. Although several studies over the last decade have demonstrated its efficacy in other Immunoglobulin E related diseases, its use in such conditions is off-label.
OBJECTIVE
This study aimed to assess the effectiveness of long-term therapy with Omalizumab in patients with persistent severe allergic rhinitis and inadequately controlled severe asthma.
METHODS
Patients with poorly controlled severe asthma and persistent allergic rhinitis were enrolled and treated with Omalizumab for 36 months with every four-week subcutaneous administration. The efficacy assessment included the severity of AR symptoms every six months using Visual Analogue Scale, Asthma Control Test, nasal endoscopy, spirometry, and biomarkers (blood eosinophils and neutrophils, fractional exhaled nitric oxide, total IgE).
RESULTS
Eleven patients aged between 26 and 70 years were enrolled, and 10 completed the study. A significant improvement of allergic rhinitis symptoms, Asthma Control Test, and lung function was observed. There was also a reduction in the status of the biomarkers at the end of the study.
CONCLUSION
Long-term therapy with Omalizumab was effective and safe in treating severe persistent allergic rhinitis and concomitant asthma.
Topics: Adult; Aged; Asthma; Biomarkers; Chronic Disease; Female; Humans; Immunoglobulin E; Male; Middle Aged; Omalizumab; Respiratory Function Tests; Retrospective Studies; Rhinitis, Allergic; Sinusitis; Th2 Cells; Time Factors; Treatment Outcome
PubMed: 32798500
DOI: 10.1016/j.imlet.2020.08.002 -
Allergy Oct 2020About 20 years after the identification of immunoglobulin E (IgE) and its key role in allergic hypersensitivity reactions against normally harmless substances,... (Review)
Review
About 20 years after the identification of immunoglobulin E (IgE) and its key role in allergic hypersensitivity reactions against normally harmless substances, scientists have started inventing strategies to block its pathophysiological activity in 1986. The initial concept of specific IgE targeting through the use of anti-IgE antibodies has gained a lot of momentum and within a few years independent research groups have reported successful generation of first murine monoclonal anti-IgE antibodies. Subsequent generation of optimized chimeric and humanized versions of these antibodies has paved the way for the development of therapeutic anti-IgE biologicals as we know them today. With omalizumab, there is currently still only one therapeutic anti-IgE antibody approved for the treatment of allergic conditions. Since its application is limited to the treatment of moderate-to-severe persistent asthma and chronic spontaneous urticaria, major efforts have been undertaken to develop alternative anti-IgE biologicals that could potentially be used in a broader spectrum of allergic diseases. Several new drug candidates have been generated and are currently assessed in pre-clinical studies or clinical trials. In this review, we highlight the molecular properties of past and present anti-IgE biologicals and suggest concepts that might improve treatment efficacy of future drug candidates.
Topics: Animals; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biological Products; Humans; Mice; Omalizumab
PubMed: 32249957
DOI: 10.1111/all.14308 -
International Journal of Molecular... Jul 2023Chronic urticaria (CU) is a debilitating skin disease affecting around 1% of the population. CU can be subdivided into chronic spontaneous urticaria (CSU) and chronic... (Review)
Review
Chronic urticaria (CU) is a debilitating skin disease affecting around 1% of the population. CU can be subdivided into chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). Different pathophysiological mechanisms have been proposed to play a role in the development of CU, and these are also being investigated as potential biomarkers in the diagnosis and management of the disease. As of now the only assessment tools available for treatment response are patient reported outcomes (PROs). Although these tools are both validated and widely used, they leave a desire for more objective measurements. A biomarker is a broad subcategory of observations that can be used as an accurate, reproducible, and objective indicator of clinically relevant outcomes. This could be normal biological or pathogenic processes, or a response to an intervention or exposure, e.g., treatment response. Herein we provide an overview of biomarkers for CU, with a focus on prognostic biomarkers for treatment response to omalizumab, thereby potentially aiding physicians in personalizing treatments.
Topics: Humans; Omalizumab; Anti-Allergic Agents; Urticaria; Treatment Outcome; Chronic Disease; Chronic Urticaria; Biomarkers
PubMed: 37511088
DOI: 10.3390/ijms241411328 -
The World Allergy Organization Journal Oct 2022Omalizumab is recommended as an add-on therapy in patients aged ≥6 years with inadequately controlled, moderate-to-severe persistent allergic asthma. The efficacy and... (Review)
Review
Omalizumab is recommended as an add-on therapy in patients aged ≥6 years with inadequately controlled, moderate-to-severe persistent allergic asthma. The efficacy and safety of omalizumab treatment in allergic asthma clinical trials and its effectiveness in the real world have been reported in numerous studies. In this review, we examine clinical evidence in pediatric and adult patients with allergic asthma who received omalizumab treatment for at least 2 years, to assess its effectiveness, durability, and trajectory of response over time as well as safety. We performed a literature search from inception until March 2022 in PubMed using the keywords "omalizumab" and "allergic asthma" to retrieve articles examining the effects of omalizumab in patients with allergic asthma, aged ≥6 years. Only articles that evaluated the effectiveness of omalizumab for at least 2 years were included. Data from case reports were excluded. Our review confirmed the long-term effectiveness and safety of omalizumab, demonstrating reduced rate of exacerbations, improved lung function, asthma control, and quality of life, decreased health care resource utilization, and use of corticosteroids (oral/inhaled) with a favorable safety and tolerability profile for up to 9 years in adult patients with moderate-to-severe allergic asthma. Similar results were also observed in the pediatric population with up to 7.5 years of omalizumab treatment. This review highlights and confirms the sustained clinical benefits of omalizumab over long periods of treatment in pediatric and adult populations with allergic asthma.
PubMed: 36254180
DOI: 10.1016/j.waojou.2022.100695 -
Therapeutic Advances in Respiratory... 2023To explore whether baseline clinical biomarkers and characteristics can be used to predict the responsiveness of omalizumab. (Observational Study)
Observational Study
OBJECTIVE
To explore whether baseline clinical biomarkers and characteristics can be used to predict the responsiveness of omalizumab.
METHODS
We retrospectively analyzed a cohort of patients with severe asthma who received omalizumab treatment and collected their baseline data and relevant laboratory examination results along with case records of omalizumab treatment responsiveness after 16 weeks. We compared the differences in variables between the group of patients that responded to omalizumab therapy and the non-responder group, and then performed univariate and multivariate logistic regression. Finally, we analyzed the difference in response rate for subgroups by selecting cut-off values for the variables using Fisher's exact probability method.
RESULTS
This retrospective, single-center observational study enrolled 32 patients with severe asthma who were prescribed daily high-dose inhaled corticosteroids and long-acting β2 receptor agonists on long-acting muscarinic receptor antagonists with or without OCS. Data on age, sex, BMI, bronchial thermoplasty, FeNO, serum total IgE, FEV1, blood eosinophils, induced sputum eosinophils, blood basophils, and complications were not significantly different between the responder and non-responder groups. In the univariate and multivariate logistic regression, all the variants were not significant, and we were unable to build a regression model. We used normal high values and the mean or median of variables as cut-off values to create patient subgroups for the variables and found no significant difference in the omalizumab response rate between the subgroups.
CONCLUSION
The responsiveness of omalizumab is not associated with pretreatment clinical biomarkers, and these biomarkers should not be used to predict the responsiveness of omalizumab.
Topics: Humans; Omalizumab; Retrospective Studies; Anti-Asthmatic Agents; Treatment Outcome; Asthma; Biomarkers
PubMed: 37148201
DOI: 10.1177/17534666231170821 -
Dermatology Practical & Conceptual Oct 2023Cytokines are key mediators in immunological and inflammatory conditions, including chronic spontaneous urticaria (CSU).
INTRODUCTION
Cytokines are key mediators in immunological and inflammatory conditions, including chronic spontaneous urticaria (CSU).
OBJECTIVES
To investigate Th1, Th2, and Th17 cytokine profiles in CSU and to evaluate the possible effect of omalizumab treatment.
METHODS
Patients who were followed up for CSU, as well as healthy volunteers, were included in the study. To assess urticaria activity, the 7-day-Urticaria Activity Score (UAS-7), the Urticaria Control Test (UCT), and the Chronic Urticaria Quality of Life Questionnaire (CU-QoL) were filled. Serum levels of IL-6, IL-17, IL-31, eotaxin, RANTES, TNF-α, and TSLP were analyzed by ELISA and compared in CSU and control groups. The patients were analyzed in two groups as the omalizumab group and the non-omalizumab group based on their treatment status.
RESULTS
Total IgE, ESR, CRP, RANTES, and TNF-a were significantly different in the overall comparison of the three groups: CSU-receiving omalizumab, CSU-not receiving omalizumab, and control groups (P <0.01, 0.015, <0.01, <0.01 and <0.01 respectively). Total IgE, CRP, RANTES, and TNF-α values were similar in those who received and did not receive omalizumab, yet these biomarkers were significantly higher in both groups than in the control group (P < 0.05). Statistical significance in ESR was observed only between the CSU-receiving omalizumab group and the control group (P = 0.01). Within the CSU patients, there was a slight but significant correlation between UCT and TNF-α (P = 0.008, r = 0.32) and IL-17 (P = 0.06, r = 0.33) levels.
CONCLUSIONS
The investigated cytokine profile in CSU patients may differ from healthy controls, particularly with the higher levels of RANTES and TNF-α, and omalizumab treatment does not seem to affect that profile in CSU patients.
PubMed: 37992372
DOI: 10.5826/dpc.1304a272 -
Frontiers in Allergy 2024The frequency of food allergies varies between 2% and 10%, depending on characteristics including age, region, race, and method of diagnosis self-reported by patients or... (Review)
Review
The frequency of food allergies varies between 2% and 10%, depending on characteristics including age, region, race, and method of diagnosis self-reported by patients or oral food challenges (OFCs). The most common allergies reported are tree nuts (1.2%), milk (1.9%), peanuts (2.2%), and shellfish (1.3%). Omalizumab injection has now been approved by the FDA for the treatment of immunoglobulin E-mediated food allergies in specific adults and children aged one year or older. This medication reduces the risk of allergic reactions (Type I), which can include anaphylaxis, when an individual accidentally encounters one or more food allergens. Omalizumab functions by binding to IgE and altering IgE-mediated pathways, which lessens IgE's capacity to cause allergic reactions. Promising outcomes from clinical trials and case studies include lowered anaphylactic risk and enhanced tolerance to allergens. Omalizumab, however, may have adverse effects; thus, close observation is required. Overall, this review sheds light on the efficacy, safety, and clinical implications of omalizumab, highlighting its potential as a useful intervention for IgE-mediated food allergies.
PubMed: 38873398
DOI: 10.3389/falgy.2024.1409342 -
International Journal of Molecular... Apr 2023The response of severe chronic spontaneous urticaria (CSU) to omalizumab largely depends on the autoimmune or autoallergic endotype of the disease. Whether thyroid...
The response of severe chronic spontaneous urticaria (CSU) to omalizumab largely depends on the autoimmune or autoallergic endotype of the disease. Whether thyroid autoimmunity may predict omalizumab response along with total IgE in CSU is still unclear. Three hundred and eighty-five patients (M/F 123/262; mean age 49.5 years; range 12-87 years) with severe CSU were studied. Total IgE levels and thyroid autoimmunity (levels of anti-thyroid peroxidase [TPO] IgG) were measured before omalizumab treatment. Based on the clinical response, patients were divided into early (ER), late (LR), partial (PR) and non (NR) responders to omalizumab. Thyroid autoimmunity was detected in 92/385 (24%) patients. Altogether, 52%, 22%, 16% and 10% of patients were ER, LR, PR and NR to omalizumab, respectively. Response to omalizumab was not associated with thyroid autoimmunity ( = 0.77). Conversely, we found a strongly positive association between IgE levels and omalizumab response ( < 0.0001); this association was largely driven by early response (OR = 5.46; 95% CI: 2.23-13.3). Moreover, the predicted probabilities of early response strongly increased with increasing IgE levels. Thyroid autoimmunity alone cannot be used as a clinical predictor of omalizumab response. Total IgE levels remain the only and most reliable prognostic marker for omalizumab response in patients with severe CSU.
Topics: Humans; Middle Aged; Omalizumab; Autoimmunity; Urticaria; Immunoglobulin E; Chronic Urticaria; Chronic Disease; Anti-Allergic Agents; Treatment Outcome
PubMed: 37108654
DOI: 10.3390/ijms24087491 -
BMC Pulmonary Medicine Oct 2023Omalizumab is a valuable alternative treatment for allergic bronchopulmonary aspergillosis (ABPA). The effectiveness and safety of this medication have not been...
BACKGROUND
Omalizumab is a valuable alternative treatment for allergic bronchopulmonary aspergillosis (ABPA). The effectiveness and safety of this medication have not been confirmed. The main purpose of this study was to evaluate the effectiveness and safety of omalizumab for ABPA.
METHODS
This study involved a retrospective chart review. The main indicators used were asthma control test (ACT) scores, lung function parameters, doses of corticosteroids, acute exacerbation, hospitalization rates, total serum immunoglobulin E (IgE) levels, and blood eosinophil counts. Related adverse events were also reviewed to evaluate the safety of omalizumab.
RESULTS
Fourteen patients with ABPA were included, of whom 10 (71%) concurrently had allergic rhinitis (AR). There were improvements in the mean percentages of the forced vital capacity, percentages of the forced expiratory volume in 1 s, and ACT score after omalizumab administration (p < 0.05, p < 0.01, and p < 0.01, respectively). After the initiation of omalizumab administration, the median corticosteroid dose, acute exacerbation rate, hospitalization rate, and mean blood eosinophil count decreased when compared with the baseline values (p < 0.05, p < 0.05, p < 0.01, and p < 0.05, respectively). A reduction in the total serum IgE level was observed in patients with ABPA without AR compared with that in patients with AR (p < 0.05). One patient reported a concurrent skin rash, which spontaneously resolved without medication.
CONCLUSION
It is safe and effective to prescribe omalizumab to patients with ABPA, irrespective of whether they have AR. Dose adjustment of omalizumab is safe after disease control. The total serum IgE level might be a predictor of the effectiveness of omalizumab in patients without AR.
Topics: Humans; Omalizumab; Anti-Allergic Agents; Aspergillosis, Allergic Bronchopulmonary; Retrospective Studies; Adrenal Cortex Hormones; Rhinitis, Allergic; Immunoglobulin E
PubMed: 37833657
DOI: 10.1186/s12890-023-02696-x -
Allergy, Asthma, and Clinical... Oct 2023Dupilumab, omalizumab, and mepolizumab are the three biologics currently approved for use in CRSwNP in Canada. Despite evidence of efficacy, their cost-effectiveness,...
BACKGROUND
Dupilumab, omalizumab, and mepolizumab are the three biologics currently approved for use in CRSwNP in Canada. Despite evidence of efficacy, their cost-effectiveness, which is a key factor influencing prescribing patterns, has not yet been compared to each other.
METHODS
A cost-effectiveness model using quality-adjusted life years (QALYs) was constructed using a Decision Tree Markov analysis. A third-party healthcare payer perspective and a 10-year time horizon was used. A willingness-to-pay (WTP) threshold of 50,000 Canadian dollars (CAD) per QALY was used to determine cost-effectiveness. Dupilumab, omalizumab, and mepolizumab were each compared to each other.
RESULTS
Omalizumab was the most cost-effective biologic using current estimates of cost and efficacy in CRSwNP. Using omalizumab as a baseline, dupilumab had an ICER of $235,305/QALY. Mepolizumab was dominated by omalizumab and dupilumab at the current drug prices and estimates of efficacy. Sensitivity analyses determined that when increasing the WTP threshold to $150,000/QALY, dupilumab became cost-effective compared to omalizumab in 22.5% of simulation scenarios. Additionally, altering dosing frequency had a significant effect on cost-effectiveness.
CONCLUSION
When comparing the relative cost-effectiveness of biologics in recalcitrant CRSwNP, omalizumab currently appears to be the most cost-effective option. Future reductions in drug prices, adjustments to currently approved dosing regimens, better patient selection, and improvements in sinus surgery outcomes will challenge the current cost-effectiveness models and necessitate reassessment as treatments for CRSwNP continue to evolve.
PubMed: 37838713
DOI: 10.1186/s13223-023-00823-1