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Antioxidants (Basel, Switzerland) Feb 2023Fractional exhaled nitric oxide (FeNO) is a biomarker of airway inflammation associated with airway hyper-responsiveness and type-2 inflammation. Its role in the... (Review)
Review
BACKGROUND
Fractional exhaled nitric oxide (FeNO) is a biomarker of airway inflammation associated with airway hyper-responsiveness and type-2 inflammation. Its role in the management of severe asthmatic patients undergoing biologic treatment, as well as FeNO dynamics during biologic treatment, is largely unexplored.
PURPOSE
The aim was to evaluate published data contributing to the following areas: (1) FeNO as a predictive biomarker of response to biologic treatment; (2) the influence of biologic treatment in FeNO values; (3) FeNO as a biomarker for the prediction of exacerbations in patients treated with biologics.
METHODS
The systematic search was conducted on the Medline database through the Pubmed search engine, including all studies from 2009 to the present.
RESULTS
Higher baseline values of FeNO are associated with better clinical control in patients treated with omalizumab, dupilumab, and tezepelumab. FeNO dynamics during biologic treatment highlights a clear reduction in FeNO values in patients treated with anti-IL4/13 and anti-IL13, as well as in patients treated with tezepelumab. During the treatment, FeNO may help to predict clinical worsening and to differentiate eosinophilic from non-eosinophilic exacerbations.
CONCLUSIONS
Higher baseline FeNO levels appear to be associated with a greater benefit in terms of clinical control and reduction of exacerbation rate, while FeNO dynamics during biologic treatment remains a largely unexplored issue since few studies have investigated it as a primary outcome. FeNO remains detectable during biologic treatment, but its potential utility as a biomarker of clinical control is still unclear and represents an interesting research area to be developed.
PubMed: 36829959
DOI: 10.3390/antiox12020400 -
The Journal of Asthma : Official... Sep 2023This meta-analysis was conducted to quantitatively pool the incremental net benefit (INB) of using biologic therapies as an add-on treatment to standard therapy in... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This meta-analysis was conducted to quantitatively pool the incremental net benefit (INB) of using biologic therapies as an add-on treatment to standard therapy in patients with moderate to severe asthma.
METHODS
We performed a comprehensive search in several databases published until April 2022. Studies were included if they were cost-effectiveness analyses reporting cost per quality-adjusted life-year or life-year on any biologic therapies as an add-on treatment for moderate to severe asthma in patients of all ages. Various monetary units were converted to purchasing power parity, adjusted to 2021 US dollars. The INBs were pooled across studies using a random-effects model, stratified by country income level (high-income countries (HICs) and low- and middle-income countries (LMICs)) and perspectives (health care or payer perspective (HCPP) and societal perspective (SP)) and age group (>12 years and 6-11 years). Heterogeneity was assessed using the I statistic.
RESULTS
A total of 32 comparisons from 25 studies were included. Pooled INB indicated that the use of omalizumab as an add-on treatment to standard therapy in those aged >12 years was not cost-effective in HICs from the HCPP ( = 8, INB, -6,341 (95% CI, -$25,000 to $12,210), I=86.18%) and SP ( = 5, -$14,000 (-$170,000 to $140,000), I=75.64%). A similar finding was observed in those aged 6-11 years from the HCPP in LMICs ( = 2, -$45,000 (-$73,000 to $17,000), I=00.00%). Subgroup analyses provided no explanations of the potential sources of heterogeneity.
CONCLUSION
The use of biologic therapies in moderate to severe asthma is not cost-effective compared to standard treatment alone.
Topics: Humans; Asthma; Cost-Benefit Analysis; Omalizumab; Biological Therapy
PubMed: 36825403
DOI: 10.1080/02770903.2023.2183407 -
The Journal of Allergy and Clinical... May 2023Antidrug antibodies (ADAs) may worsen the efficacy and safety of biologics. However, little is known about the incidence of ADAs associated with the 6 biologics approved... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antidrug antibodies (ADAs) may worsen the efficacy and safety of biologics. However, little is known about the incidence of ADAs associated with the 6 biologics approved for the treatment of asthma in the United States.
OBJECTIVE
To elucidate the incidence of ADAs and their impact on reported clinical outcomes.
METHODS
Systematic review and meta-analyses of randomized controlled trials, open-label extension studies, and nonrandomized studies of biologics in patients with asthma indexed in PubMed, Embase, and CENTRAL between January 1, 2000, and July 9, 2022, were carried out. The primary outcomes were treatment-emergent ADAs (incidence) and ADA prevalence.
RESULTS
A total of 46 studies met the eligibility criteria. ADA incidence over follow-up was 2.91% (95% CI, 1.60-4.55) and was highest in the benralizumab studies (8.35%), with a risk ratio of 4.9 (2.69-8.92) when compared with placebo, and lowest in the omalizumab studies (0.00%). Incidence was 7.61% in the dupilumab studies, 4.39% in reslizumab, 3.63% in mepolizumab, and 1.12% in the tezepelumab studies. Incidence of neutralizing antibodies was 0.00% to 10.74% and was highest for benralizumab (7.12%). Incidence of neutralizing antibodies was higher in the benralizumab every 8 weeks (8.17%) versus every 4 weeks arms (5.81%). Results were consistent in subgroup analyses by study type and length of follow-up.
CONCLUSIONS
Approximately 2.9% of individuals in the included studies developed ADAs over study follow-up period. The incidence was highest in the benralizumab group and lowest in the omalizumab group. The subcutaneous route and longer dosing intervals were associated with higher ADA development.
Topics: Humans; Antibodies, Monoclonal; Omalizumab; Incidence; Asthma; Biological Products; Antibodies, Neutralizing; Anti-Asthmatic Agents
PubMed: 36716995
DOI: 10.1016/j.jaip.2022.12.046 -
Biomolecules Jan 2023A recent report showed that most pediatric cases of non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal disorders (EGIDs) (non-EoE EGIDs) are persistent and...
Dupilumab Leads to Clinical Improvements including the Acquisition of Tolerance to Causative Foods in Non-Eosinophilic Esophagitis Eosinophilic Gastrointestinal Disorders.
A recent report showed that most pediatric cases of non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal disorders (EGIDs) (non-EoE EGIDs) are persistent and severe compared with those of EoE, thus requiring further effective therapeutic approaches. In this study, we present the first case based on a systematic search of non-EoE EGID for which tolerance to causative foods and histological and symptomatic improvements were achieved following dupilumab administration, after elimination diets and omalizumab and mepolizumab treatments. Driven by this case, we investigated the efficacies of biological treatments in non-EoE EGID cases based on the patient studied herein, and other patients identified in the conducted systematic review. Seven articles, including five different biologics, were reviewed. Both clinical efficacies and impact differences among the targeted molecules are demonstrated in this study. Our findings show that dupilumab may affect mechanisms that can suppress symptoms induced by offending foods that are different from those induced by other biologics as identified in the conducted systematic review. Additional studies are required to address the unmet needs of non-EoE EGID treatments.
Topics: Child; Humans; Biological Products; Esophagitis; Treatment Outcome; Immune Tolerance
PubMed: 36671497
DOI: 10.3390/biom13010112 -
The World Allergy Organization Journal Feb 2023Omalizumab which downregulates the immunoglobulin E (IgE) receptor site on plasmacytoid dendritic cells and thereby increases interferon-α (INF-α) production, may... (Review)
Review
Omalizumab which downregulates the immunoglobulin E (IgE) receptor site on plasmacytoid dendritic cells and thereby increases interferon-α (INF-α) production, may shorten the duration of viral infections by enhancing the antiviral immunity. A systematic review was conducted to investigate whether previous anti-IgE treatment with omalizumab could protect against SARS-CoV-2 disease ("COVID-19") (infection, disease duration, and severity), and whether IFN-α upregulation could be involved. The research included articles published from March 2020 to January 2022. An accurate search was performed on bibliographic biomedical database (MEDLINE - Pubmed, SCOPUS, EMBASE, BIOMED CENTRAL, Google scholar, COCHRANE LIBRARY, ClinicalTrial.gov) including cohorts, case reports and reviews. Different methods were used, based on the study design, to assess the quality of eligible studies. Several authors link omalizumab to a possible protection against viruses, but they often refer to studies carried out before the pandemic and with viruses other than SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) (eg, rhinoviruses -RV). Few cases of COVID-19 patients treated with omalizumab have been recorded, and, in most of them, no increased susceptibility to severe disease was observed. According to these data, the current indication is to continue omalizumab therapy during the pandemic. Moreover, although omalizumab may enhance the antiviral immune response even for SARS-CoV-2, further studies are needed to confirm this hypothesis. It would be helpful to establish a registry of omalizumab-treated (or in treatment) patients who have developed COVID-19. Finally, randomized controlled trials could be able to demonstrate the effect of omalizumab in protecting against severe SARS-CoV-2, through IFN-α upregulation or other immunological pathways.
PubMed: 36644451
DOI: 10.1016/j.waojou.2023.100741 -
The Journal of Allergy and Clinical... Mar 2023An unmet clinical need exists in the management of treatment-refractory allergic bronchopulmonary aspergillosis (ABPA). Omalizumab has shown promising effects in case... (Meta-Analysis)
Meta-Analysis
BACKGROUND
An unmet clinical need exists in the management of treatment-refractory allergic bronchopulmonary aspergillosis (ABPA). Omalizumab has shown promising effects in case series and cohort studies; however, evidence to support its routine clinical use is lacking.
OBJECTIVE
The aim of this systematic review and meta-analysis was to evaluate the clinical effectiveness and safety of omalizumab in patients with ABPA.
METHODS
We conducted a systematic search across standard databases using specific key words until May 13, 2021. We performed a meta-analysis to compare the effectiveness (exacerbations, oral corticosteroid [OCS] use, lung function, and patient-reported asthma control) and safety of pre- and post-omalizumab treatment. Subgroup analyses were performed for treatment duration and underlying disease.
RESULTS
In total, 49 studies (n = 267) were included in the qualitative synthesis and 14 case series (n = 186) in the quantitative meta-analysis. Omalizumab treatment significantly reduced the annualized exacerbation rate compared with pretreatment (mean difference, -2.09 [95% CI, -3.07 to -1.11]; P < .01). There was a reduction in OCS use (risk difference, 0.65 [95% CI, 0.46-0.84]; P < .01), an increase in termination of OCS use (risk difference, 0.53 [95% CI, 0.24-0.82]; P < .01), and a reduction in OCS dose (milligrams per day) (mean difference, -14.62 [95% CI, -19.86 to -9.39]; P < .01) in ABPA patients receiving omalizumab. Omalizumab improved FEV % predicted by 11.9% (95% CI, 8.2-15.6; P < .01) and asthma control, and was well-tolerated.
CONCLUSIONS
Omalizumab treatment reduced exacerbations and OCS use, improved lung function and asthma control in patients with ABPA, and was well-tolerated. The results highlight the potential role of omalizumab in the treatment of ABPA.
Topics: Humans; Omalizumab; Aspergillosis, Allergic Bronchopulmonary; Cystic Fibrosis; Asthma; Adrenal Cortex Hormones
PubMed: 36581073
DOI: 10.1016/j.jaip.2022.12.012 -
The Journal of Allergy and Clinical... Apr 2023A growing number of studies have shown encouraging results with omalizumab (OMA) as monotherapy and as an adjunct to oral immunotherapy (OMA+OIT) in patients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A growing number of studies have shown encouraging results with omalizumab (OMA) as monotherapy and as an adjunct to oral immunotherapy (OMA+OIT) in patients with single/multiple food allergies.
OBJECTIVES
To evaluate the efficacy and safety of OMA or OMA+OIT in patients with immunoglobulin E (IgE)-mediated food allergy.
METHODS
An extensive literature search (inception to December 31, 2020) was performed to identify randomized, controlled, and observational studies that assessed OMA as monotherapy or OMA+OIT in patients with IgE-mediated food allergy. The outcomes were an increase in tolerated dose of foods, successful desensitization, sustained unresponsiveness, immunological biomarkers, severity of allergic reactions to food, quality of life (QoL), and safety. A P less than .05 was considered significant.
RESULTS
In total, 36 studies were included. The OMA monotherapy (vs pre-OMA) significantly increased the tolerated dose of multiple foods; increased the threshold of tolerated dose for milk, egg, wheat, and baked milk; improved QoL; and reduced food-induced allergic reactions (all P < .01). The OMA+OIT significantly increased the tolerated dose of multiple foods (vs placebo and pre-OMA), desensitization (vs placebo+OIT and pre-OMA) (all P ≤ .01), and improved QoL (vs pre-OMA) and immunoglobulin G4 levels (both P < .01). No major safety concerns were identified.
CONCLUSIONS
In IgE-mediated food allergy, OMA can help patients consume multiple foods and allow for food dose escalation. As an adjunct to OIT, OMA can also support high-dose desensitization and higher maintenance doses. Further studies are warranted to empirically evaluate the effect of OMA and confirm these findings.
Topics: Humans; Animals; Omalizumab; Quality of Life; Immunoglobulin E; Desensitization, Immunologic; Administration, Oral; Food Hypersensitivity; Allergens; Milk
PubMed: 36529441
DOI: 10.1016/j.jaip.2022.11.036 -
Journal of Asthma and Allergy 2022Data specific to the epidemiology, clinical features, and management of chronic urticaria (CU) in the geriatric population remain limited and not well understood. We aim... (Review)
Review
PURPOSE
Data specific to the epidemiology, clinical features, and management of chronic urticaria (CU) in the geriatric population remain limited and not well understood. We aim to systematically review the prevalence, clinical manifestations, treatment, and clinical course of elderly patients with CU.
PATIENTS AND METHODS
Original articles that included data of elderly (aged >60 years) with CU that were published until February 2021 were searched in PubMed, Scopus, and Embase using predfefined search terms. Related articles were evaluated according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.
RESULTS
Among the included 85 studies and 1,112,066 elderly CU patients, most (57.4%) were women. The prevalence of elderly CU in the general population ranged from 0.2-2.8%, and from 0.7-33.3% among all CU patients. Compared to adult CU, elderly CU patients had a higher percentage of wheal alone (73.9%), and lower rate of positive autologous serum skin test and atopy. Gastrointestinal diseases were the most common comorbidity (71.9%), and there was a high rate of malignancies and autoimmune diseases. Second generation H-antihistamines were commonly used, and achievement of complete control was most often reported. Omalizumab was prescribed in 59 refractory patients, and a significant response to treatment was reported in most patients. The treatment of comorbidities also yielded significant improvement in CU.
CONCLUSION
Elderly CU was found to be different from adult CU in both clinical and laboratory aspects. H- antihistamines are effective as first-line therapy with minimal side-effects at licensed doses. Treatment of secondary causes is important since the elderly usually have age-related comorbidities.
PubMed: 36299736
DOI: 10.2147/JAA.S379912 -
Frontiers in Pharmacology 2022Asthma drug research has been increasing yearly, and its clinical application value has increasingly attracted attention. This study aimed to analyze the development...
Asthma drug research has been increasing yearly, and its clinical application value has increasingly attracted attention. This study aimed to analyze the development status, research hotspots, research frontiers, and future development trends of the research works on drugs for patients with asthma, especially severe asthma. Asthma drug-related articles published between 1982 and 2021 were retrieved from the Web of Science Core Collection (WOSCC) database, and only articles published in English were included. CiteSpace and VOSviewer software were utilized to conduct collaborative network analysis of countries/regions, institutions, keywords, and co-citation analysis of references. A total of 3,234 asthma drug-related eligible articles were included. The United States was in a leading position, and Karolinska Institute (Sweden) was the most active institution. The most prolific journal in this field was , and the most cited journal was . Keyword co-occurrence studies suggested that the current hotspots and frontiers were as follows: ① asthma: fully revealing the potential of existing conventional asthma drugs, determining the best drug delivery system, and indicating the best combination. To continue to explore potential targets for severe asthma or other phenotypes. Inhaled glucocorticoids and budesonide are still one of the important aspects of current asthma drug research and ② severe asthma: the research and development of new drugs, especially monoclonal antibodies including omalizumab, mepolizumab, and benralizumab to improve asthma control and drug safety, have become a research hotspot in recent years, highlighting the importance of "target" selection. This study demonstrates the global research hotspots and trends of the research works on drugs for patients with asthma/severe asthma. It can help scholars quickly understand the current status and hotspots of research in this field.
PubMed: 36263119
DOI: 10.3389/fphar.2022.916871 -
Dermatologic Therapy Dec 2022This meta-analysis aimed to assess the efficacy of omalizumab in the treatment of refractory-to-antihistamines chronic induced urticaria (CIndU) in comparison with that... (Meta-Analysis)
Meta-Analysis Review
This meta-analysis aimed to assess the efficacy of omalizumab in the treatment of refractory-to-antihistamines chronic induced urticaria (CIndU) in comparison with that of refractory-to-antihistamines chronic spontaneous urticaria (CSU). We retrieved interventional studies and observational studies on omalizumab efficacy to CIndU patients and efficacy comparison between CSU and CIndU both refractory to H1-antihistamines in electronic databases (accessed till May 2022). The odd ratio (OR) and 95% confidence interval (CI) was calculated with a random-effect model in this meta-analysis. The majority of patients with different CIndU subtypes gained complete or partial response and good safety after omalizumab treatment. A total of five studies with 355 CSU patients and 103 CIndU patients were included for the meta-analysis. There was no significant difference in the efficacy of omalizumab in the treatment of CSU and CIndU (OR -0.83, 95% CI [0.84, 2.21], P > 0.05). Based on the validity of omalizumab in the treatment of various CIndU subtypes and non-differential efficacy between CSU and CIndU, it is reasonable to list omalizumab as a third-line treatment of refractory CIndU.
Topics: Humans; Omalizumab; Anti-Allergic Agents; Urticaria; Chronic Disease; Chronic Urticaria; Histamine Antagonists; Treatment Outcome
PubMed: 36222320
DOI: 10.1111/dth.15928