RESUMO
BACKGROUND: The concept of remission on biological treatment has been suggested as a therapeutic target for patients with severe asthma, composed of 1. no chronic use of systemic steroids, 2. no exacerbations, 3. minimal symptoms, and 4. optimized lung function, for a significant time. However, the criteria for remission are not clearly defined. OBJECTIVE: Our objective was to compare different criteria for remission in subjects receiving biologicals for severe asthma. METHODS: A cross-sectional study of adult subjects who receive a stable regimen of a biological for severe asthma for at least 6-months. We compared the proportion of subjects who fulfilled different specific criteria in the four domains, as well as those who achieved different composite outcome measures of clinical remission. RESULTS: Of 39 subjects, 28 were females (71.8%), mean age 60.4. Twelve were current or past smokers (30.8%). Twelve had prior different biological treatment (30.8%), and 3/39 had more than one previous treatment (7.7%). Current biological included mepolizumab 12/39 (30.8%), dupilumab 11/39 (28.2%), benralizumab 10/39 (25.6%), omalizumab 5/39 (12.8%), reslizumab 1/39 (2.6%). Different specific criteria were achieved in 39-80% of subjects, being highest for no chronic steroid use and lowest for symptoms control and lung function. Overall remission was obtained by 20-41%, depending on definition, with significant variability in agreement between different sets of remission criteria (Cohen's kappa 0.33-0.89). CONCLUSION: Clinical remission is achievable in real-world severe asthmatics on biological therapies. The core criteria for remission should be better defined.
Assuntos
Antiasmáticos , Asma , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Antiasmáticos/uso terapêutico , Estudos Transversais , Omalizumab/uso terapêutico , Terapia BiológicaRESUMO
A substantial portion of asthma and nasal polyps (NPs) share a common pathogenesis, which includes type 2-mediated inflammation. Distinct endotypes and phenotypes characterizing asthma and chronic rhinosinusitis have been identified. With emerging evidence describing pathophysiology, novel targets for biologic monoclonal antibody treatments have been developed. There are currently six biologic therapies approved by the US Food and Drug Administration to treat asthma, including omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab, three of these-omalizumab, mepolizumab, and dupilumab-are also approved for NPs.
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Asma , Pólipos Nasais , Estados Unidos , Humanos , Omalizumab/uso terapêutico , Asma/tratamento farmacológico , Pólipos Nasais/tratamento farmacológico , Terapia BiológicaRESUMO
INTRODUCTION: Asthma is one of the most common diseases in children, with a variable range of severity. In recent years, treatment for severe asthma has been largely improved by the availability of targeted biologic therapies. Nevertheless, studies reporting real-world data and cost-effectiveness analyses are lacking. The aim of this study was to evaluate, on a population-based cohort of children with asthma, the impact of the treatment with biologics on healthcare service utilization and associated costs. METHODS: Data were retrieved from Healthcare Utilization database of Lombardy region (Italy). A cohort of 46 asthmatic children aged 6-11 in treatment with dupilumab, mepolizumab or omalizumab was identified during 2017-2021. We compared healthcare resources use between the year before ("baseline period") and the year after the treatment initiation ("follow-up period"). Average 1-year healthcare costs were also calculated. RESULTS: Comparing the baseline with the follow-up period, the number of patients with at least one exacerbation-related hospitalization and ER access decreased by 75.0% and 85.7%, respectively. The use of biologic agents, namely omalizumab, mepolizumab and dupilumab, significantly reduced oral corticosteroids (OCS), short-acting ß2-agonists and the association inhaled corticosteroids/long-acting ß2-agonists use. ER admissions for non-respiratory causes were also significantly reduced, while discontinuation rate was low (6.5%). The overall costs increased, due to the costs of the biologic agents, but the hospital admission-related costs due to respiratory causes reduced significantly. CONCLUSIONS: Our real-world investigation suggests that biologic agents reduced hospital admissions for respiratory causes and use of anti-asthmatic drugs, including OCS. However, long-term healthcare sustainability still needs more in-depth assessments.
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Antiasmáticos , Asma , Criança , Humanos , Omalizumab/uso terapêutico , Estudos de Coortes , Asma/tratamento farmacológico , Custos de Cuidados de Saúde , Terapia Biológica , Corticosteroides/uso terapêuticoRESUMO
INTRODUCTION: The possible influence of sensitization to aeroallergens on omalizumab response in chronic spontaneous urticaria (CSU) has been insufficiently investigated. This study's aim was to investigate atopy's influence on omalizumab response in CSU patients. METHOD: Retrospective study of CSU patients followed at a Portuguese Urticaria Center of Reference and Excellence (UCARE), treated with omalizumab for at least 6 months, between 2015 and 2022. At T0, all patients underwent quantification of specific immunoglobulin E (IgE) for total extract of most prevalent aeroallergens (ImmunoCAP Thermo Fisher Scientific®) and were divided in 2 groups, according to their response to omalizumab during the first 16 weeks of treatment: responders (R) (UAS7 <7) versus partial (PR) (UAS7 = 7-15) and nonresponders (UAS7 >15). R were further classified as fast (FR) (4-6 weeks) and slow responders (SR) (12-16 weeks). Total serum IgE, circulating eosinophil, and basophil counts were compared between groups at T0. p < 0.05 was considered statistically significant (SPSS® v25.0). RESULTS: Ninety-six patients (80% female) were studied, mean age 49 ± 14 years. Median CSU duration pre-omalizumab was 3 (0.6-20) years and mean omalizumab treatment duration was 3.7 ± 2.3 years. 38 (40%) had concomitant chronic inducible urticaria and 72 (75%) angioedema. Based on positive results of the specific IgE assay, 35 patients (36%) were considered atopic. Most patients (n = 30; 86%) were sensitized to house dust mites (HDM) (Dermatophagoides farinae = 28, Dermatophagoides pteronyssinus = 27, Blomia tropicalis = 19, Lepidoglyphus destructor = 17), followed by pollens (n = 12; 34%) (mixture of grasses = 10, Olea europaea = 7, Parietaria officinalis = 6), epithelia (n = 9; 26%) (dog = 8, cat = 7), and fungi (Alternaria alternata = 4; 11%). Eight patients (23%) were monosensitized to HDM and 4 (11%) to pollens. No significant association was found between aeroallergen sensitization and CSU duration, concomitant chronic inducible urticaria, or angioedema. Atopic patients featured significantly higher levels of baseline total serum IgE than nonatopic (469 vs. 94 U/mL, respectively; p = 0.0009). Mean baseline counts of eosinophils and basophils were not significantly different between atopic and non-atopic, respectively: eosinophils (128 vs. 121/mm3) and basophils (26 vs. 28/mm3). Regarding response to omalizumab, most patients (58; 60%) were responders: FR - 46 (79%); SR - 12 (21%). There was no significant association between aeroallergen sensitization and omalizumab response or speed of response. CONCLUSIONS: As far as we know, this is the first study exploring the influence of atopy sensitization pattern on omalizumab response in CSU. According to our results, presence of atopy/sensitization pattern does not influence omalizumab response in CSU patients.
Assuntos
Angioedema , Antialérgicos , Urticária Crônica , Urticária , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antialérgicos/uso terapêutico , Doença Crônica , Urticária Crônica Induzida , Urticária Crônica/tratamento farmacológico , Imunoglobulina E , Omalizumab/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Urticária/tratamento farmacológicoRESUMO
Asthma is a chronic inflammatory condition that affects the lung airways. Chronic use of oral glucocorticoids in patients with severe asthma is associated with several adverse events (AEs). Biologics (omalizumab, benralizumab, mepolizumab, reslizumab, and dupilumab) have been developed as alternative therapies for the treatment of asthma. In this study, we aimed to evaluate the risk of anaphylactic reactions associated with these five biologics based on a large global database. We utilized individual case reports from the Uppsala Monitoring Center from January 1968 to December 29, 2019. A disproportionality analysis was performed over all drugs and monoclonal antibodies. Anaphylactic reactions were defined according to the "anaphylactic reaction" of the standardized MedDRA queries. Contrary to dupilumab, omalizumab, benralizumab, and mepolizumab demonstrated positive signals related to anaphylactic reactions over all drugs and monoclonal antibodies. Reslizumab, which represented only 315 cases of all AEs, requires more reports to determine its association with anaphylactic reactions. More anaphylactic reactions have been identified than are known, and most cases (96.2%) are reported to be serious. Our findings indicate that omalizumab, benralizumab, and mepolizumab for asthma treatment are associated with a high risk of anaphylactic reactions; thus, more careful monitoring in the post-administration period is recommended.
Assuntos
Anafilaxia , Antiasmáticos , Asma , Produtos Biológicos , Humanos , Omalizumab/efeitos adversos , Antiasmáticos/efeitos adversos , Produtos Biológicos/efeitos adversos , Farmacovigilância , Anafilaxia/induzido quimicamente , Anafilaxia/tratamento farmacológico , Anticorpos Monoclonais/uso terapêuticoRESUMO
Currently, three classes of monoclonal antibodies targeting type 2 inflammation pathways are available in Italy for the treatment of severe asthma: anti-IgE (Omalizumab), anti-IL-5/anti-IL-5Rα (Mepolizumab and Benralizumab), and anti-IL-4Rα (Dupilumab). Numerous randomized controlled trials (RCTs) and real-life studies have been conducted to define their efficacy and identify baseline patients' characteristics potentially predictive of favorable outcomes. Switching to another monoclonal antibody is recommended in case of a lack of benefits. The aim of this work is to review the current knowledge on the impact of switching biological therapies in severe asthma as well as on predictors of treatment response or failure. Almost all of the information about switching from a previous monoclonal antibody to another comes from a real-life setting. In the available studies, the most frequent initial biologic was Omalizumab and patients who were switched because of suboptimal control with a previous biologic therapy were more likely to have a higher baseline blood eosinophil count and exacerbation rate despite OCS dependence. The choice of the most suitable treatment may be guided by the patient's clinical history, biomarkers of endotype (mainly blood eosinophils and FeNO), and comorbidities (especially nasal polyposis). Due to overlapping eligibility, larger investigations characterizing the clinical profile of patients benefiting from switching to different monoclonal antibodies are needed.
Assuntos
Antiasmáticos , Asma , Humanos , Omalizumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Terapia Biológica , EosinófilosRESUMO
Recent guideline on the management of urticaria recommends second-generation H1-antihistamine as the first-line therapy, with dose increases of up to fourfold if inadequately controlled. However, the treatment of chronic spontaneous urticaria (CSU) is often disappointing, so additional adjuvant therapies are needed to increase the effectiveness of first-line therapy, especially in patients who are refractory to the increase of antihistamine doses. Recent studies recommend various adjuvant therapy modalities for CSU, such as biological agents, immunosuppressants, leukotriene receptor antagonists, H2-antihistamine, sulfones, autologous serum therapy, phototherapy, vitaminD, antioxidants, and probiotics. This literature review was made to determine the effectiveness of various adjuvant therapies in managing CSU.
Assuntos
Urticária Crônica , Urticária , Humanos , Doença Crônica , Urticária Crônica/induzido quimicamente , Urticária Crônica/tratamento farmacológico , Urticária/tratamento farmacológico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Terapia Combinada , Omalizumab/uso terapêuticoRESUMO
BACKGROUND: There are no prospective studies comparing how biological therapies affect nonsteroidal anti-inflammatory drug (NSAID) tolerance in NSAID-exacerbated respiratory disease. OBJECTIVE: To study the induction of NSAID tolerance after biological therapy in patients with NSAID-exacerbated respiratory disease. METHODS: A prospective pilot study in a real-world clinic setting was conducted among subjects with severe asthma and type 2 inflammation. A random allocation of therapy was carried out: benralizumab, dupilumab, mepolizumab, or omalizumab. NSAID intolerance was confirmed by an oral challenge test (OCT) using acetyl-salicylic acid (ASA-OCT). The principal outcome was NSAID tolerance according to OCT before and after 6 months of each biological therapy (intragroup comparisons). As exploratory outcomes, we compared NSAID tolerance between biological therapies (intergroup comparisons). RESULTS: A total of 38 subjects were included; 9 received benralizumab, 10 dupilumab, 9 mepolizumab, and 10 omalizumab. There was an increase in the concentration needed to produce a reaction during ASA-OCT with omalizumab (P < .001) and dupilumab (P = .004) but not with mepolizumab and benralizumab. Omalizumab and dupilumab achieved the highest frequency of NSAID tolerance (omalizumab 60%, dupilumab 40%, mepolizumab 22%, and benralizumab 22%). CONCLUSIONS: Biological therapies for asthma are useful for inducing NSAID tolerance; however, in patients with type 2 inflammation and high levels of total IgE, atopy, and eosinophils, anti-IgE or anti-IL4/13 seem to be more effective than antieosinophilic therapies. Omalizumab and dupilumab increased ASA tolerance, whereas mepolizumab and benralizumab did not. Future trials will be able to clarify this finding.
Assuntos
Asma , Transtornos Respiratórios , Humanos , Omalizumab/uso terapêutico , Projetos Piloto , Anti-Inflamatórios não Esteroides/efeitos adversos , Asma/tratamento farmacológico , Aspirina/uso terapêutico , Terapia Biológica , Inflamação/tratamento farmacológicoRESUMO
BACKGROUND: Oral immunotherapy (OIT) is limited by adverse events, and most patients require continued treatment to maintain their increased threshold. Adjunctive treatments have been explored to increase the safety and efficacy of OIT. OBJECTIVE: This study aimed to determine the safety and efficacy of enhanced, butanol purified Food Allergy Herbal Formula-2 (E-B-FAHF-2) for inducing remission in subjects undergoing omalizumab-facilitated multiallergen OIT (multi-OIT). METHODS: In this double-blind, placebo-controlled clinical trial, subjects were randomized 1:1 to receive either E-B-FAHF-2 or placebo, starting 2 months before OIT and continuing throughout OIT. All subjects received a 4-month course of omalizumab, starting 2 months before OIT through the 2-month OIT build-up phase. After 24 months of multi-OIT (maintenance dose of 1000 mg of each allergen), desensitization and remission were assessed. The primary objective was to determine if subjects in the E-B-FAHF-2 group (EOIT) were more likely than the placebo group (OIT) to develop remission to all 3 allergens treated with multi-OIT, as defined by the absence of dose-limiting symptoms to a cumulative dose of 4444 mg of protein after discontinuing treatment for 3 months. RESULTS: Thirty-three subjects were randomized. A total of 63.6% were desensitized to 4444 mg of protein for each allergen at 26 months, and 24.2% met the primary outcome of remission at 29 months, with no difference between the treatment groups. There was good adherence (>85%) with study medications, with no difference between the treatment groups. There was no difference in reported overall adverse events between the treatment groups. CONCLUSION: Omalizumab-facilitated multifood OIT was safe and effective, and remission was achieved in about a quarter of subjects. However, outcomes were not improved by the addition of E-B-FAHF-2.
Assuntos
Omalizumab , Hipersensibilidade a Amendoim , Humanos , Omalizumab/uso terapêutico , Dessensibilização Imunológica/efeitos adversos , Butanóis , Administração Oral , 1-Butanol , Alérgenos/uso terapêutico , Método Duplo-Cego , Hipersensibilidade a Amendoim/terapiaRESUMO
Recent guideline on the management of urticaria recommends second-generation H1-antihistamine as the first-line therapy, with dose increases of up to fourfold if inadequately controlled. However, the treatment of chronic spontaneous urticaria (CSU) is often disappointing, so additional adjuvant therapies are needed to increase the effectiveness of first-line therapy, especially in patients who are refractory to the increase of antihistamine doses. Recent studies recommend various adjuvant therapy modalities for CSU, such as biological agents, immunosuppressants, leukotriene receptor antagonists, H2-antihistamine, sulfones, autologous serum therapy, phototherapy, vitamin D, antioxidants, and probiotics. This literature review was made to determine the effectiveness of various adjuvant therapies in managing CSU.
Assuntos
Urticária Crônica , Urticária , Humanos , Doença Crônica , Urticária Crônica/induzido quimicamente , Urticária Crônica/tratamento farmacológico , Urticária/tratamento farmacológico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Terapia Combinada , Omalizumab/uso terapêuticoRESUMO
Background: Bronchial asthma (asthma) is a chronic inflammatory disease of the airways, involving a variety of cells and cellular components, that manifests clinically as recurrent episodes of wheezing, shortness of breath, with or without chest tightness or cough, airway hyperresponsiveness, and variable airflow limitation. The number of people with asthma has reached 358 million worldwide and asthma causes huge economic loss. However, there is a subset of patients who are not sensitive to existing drugs and the existing drugs have many adverse effects. Therefore, it's important to find new drugs for asthma patients. Methods: Publications related to biologics in asthma published from 2000 to 2022 were retrieved from Web of Science Core Collection. The search strategies were as follows: topic: TS=(biologic* OR "biologic* product*" OR "biologic* therap*" OR biotherapy* OR "biologic* agent*" OR Benralizumab OR "MEDI-563" OR Fasenra OR "BIW-8405" OR Dupilumab OR SAR231893 OR "SAR-231893" OR Dupixent OR REGN668 OR "REGN-668" OR Mepolizumab OR Bosatria OR "SB-240563" OR SB240563 OR Nucala OR Omalizumab OR Xolair OR Reslizumab OR "SCH-55700" OR SCH55700 OR "CEP-38072" OR CEP38072 OR Cinqair OR "DCP-835" OR DCP835 OR Tezspire OR "tezepelumab-ekko" OR "AMG-157" OR tezspire OR "MEDI-9929" OR "MEDI-19929" OR MEDI9929 OR Itepekimab OR "REGN-3500"OR REGN3500 OR "SAR-440340"OR SAR440340 OR Tralokinumab OR "CAT-354" OR Anrukinzumab OR "IMA-638" OR Lebrikizumab OR "RO-5490255"OR "RG-3637"OR "TNX-650"OR "MILR1444A"OR "MILR-1444A"OR"PRO301444"OR "PRO-301444"OR Pitrakinra OR altrakincept OR "AMG-317"OR"AMG317" OR Etokimab OR Pascolizumab OR "IMA-026"OR Enokizumab OR "MEDI-528"OR "7F3COM-2H2" OR 7F3COM2H2 OR Brodalumab OR "KHK-4827" OR "KHK4827"OR "AMG-827"OR Siliq OR Ligelizumab OR "QGE-031" OR QGE031 OR Quilizumab OR Talizumab OR "TNX-901" OR TNX901 OR Infliximab OR Etanercept OR "PRS-060") AND TS=asthma*. The document type was set to articles and review articles and the language restriction was set to English. Three different analysis tools including one online platform, VOS viewer1.6.18, and CiteSpace V 6.1.R1 software were used to conduct this bibliometric study. Results: This bibliometric study included 1,267 English papers published in 244 journals from 2,012 institutions in 69 countries/regions. Omalizumab, benralizumab, mepolizumab, and tezepelumab in relation to asthma were the research hotspots in the field. Conclusion: This study systematically uncovers a holistic picture of existing literature related to the biologic treatment of asthma over the past 20 years. We consulted scholars in order to understand key information in this field from the perspective of bibliometrics, which we believe may greatly facilitate future research in this field.
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Asma , Produtos Biológicos , Humanos , Omalizumab/uso terapêutico , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , BibliometriaRESUMO
Airway hyperresponsiveness refers to an exaggerated bronchial constrictor response to a given exogenous inhaled agent and is governed by airway smooth muscle along with mucosal inflammation in asthma. In recent years, the advent of biologics and antialarmins has transformed severe asthma treatment in terms of reducing oral-corticosteroid-requiring exacerbations and improving disease control, asthma quality of life, and spirometry-measured lung function. In contrast, there have been comparatively fewer studies investigating the efficacy of biologics in airway hyperresponsiveness. In this focused review, we summarize the existing evidence base in this area regarding omalizumab, mepolizumab, benralizumab, and tezepelumab.
Assuntos
Antiasmáticos , Asma , Produtos Biológicos , Humanos , Antiasmáticos/uso terapêutico , Qualidade de Vida , Omalizumab/uso terapêutico , Terapia Biológica , Produtos Biológicos/uso terapêuticoRESUMO
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 I2 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 (n = 8, INB, -6,341 (95% CI, -$25,000 to $12,210), I2=86.18%) and SP (n = 5, -$14,000 (-$170,000 to $140,000), I2=75.64%). A similar finding was observed in those aged 6-11 years from the HCPP in LMICs (n = 2, -$45,000 (-$73,000 to $17,000), I2=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.
Assuntos
Asma , Humanos , Asma/tratamento farmacológico , Análise Custo-Benefício , Omalizumab/uso terapêutico , Terapia BiológicaRESUMO
Pollen-food allergy syndrome (PFAS) is an immunoglobulin E (IgE)-mediated allergic reaction caused when patients with pollen allergy ingest food having cross-reactivity with pollen. To date, no effective treatment method for this has been established. Here we report the case of a patient with PFAS who experienced lip edema, causing difficulties in treatment. This report describes the case of a 12-year-old boy with perennial allergic rhinitis since the age of 8 years. After ingesting fresh fruits and raw vegetables at the age of 11 years, he started to experience lip edema repeatedly. Thus, the patient was referred to our department. Based on the results of serum antigen-specific IgE, prick-to-prick, and allergen component tests, he was diagnosed with PFAS. He has been instructed to avoid causative food. Furthermore, the treatment using an antihistamine and antileukotriene receptor antagonist was initiated for pollen allergy. Sublingual immunotherapy (SLIT) for Japanese cedar pollen was initiated because the patient experienced severe nasal allergy symptoms during the dispersal season of this pollen. These treatments alleviated the nasal symptoms; however, the lip edema persisted. Omalizumab administration improved the lip edema. The combination of SLIT and omalizumab may be an effective treatment option for patients with PFAS.
Assuntos
Angioedema , Fluorocarbonos , Hipersensibilidade Alimentar , Rinite Alérgica Sazonal , Masculino , Humanos , Criança , Rinite Alérgica Sazonal/complicações , Rinite Alérgica Sazonal/tratamento farmacológico , Omalizumab/uso terapêutico , Lábio , Pólen , Alérgenos , Hipersensibilidade Alimentar/complicações , Hipersensibilidade Alimentar/tratamento farmacológico , Síndrome , Imunoglobulina E , Edema/etiologia , Edema/terapiaRESUMO
INTRODUCTION: Treatment with biologics has significantly reduced the social and economic burden of severe asthma. However, some patients may still feature a suboptimal control of their symptoms while on therapy. In this subset of asthmatic patients, a benefit from a dual biologic therapy has sporadically been reported in literature. Our aim is to add our experience to the limited body of evidence supporting combination biologic therapies. CASE STUDY: Here we present the case of a 68-year-old nonsmoker female, with an allergic and eosinophilic corticosteroid-dependent severe asthma. She displayed well controlled comorbidities and good adherence to the inhaled therapy. Omalizumab was started in 2008 with an initial remarkable clinical improvement. After nine years of biologic therapy, she reported a gradual worsening of her symptoms and exacerbations. Mepolizumab was then added in 2019. RESULTS: The addition of Mepolizumab resulted in a meaningful amelioration of her quality of life, asthma control, number of exacerbations and 6-minute-walking-distance at 3-year follow-up. The average Prednisone dosage was tapered from 25 mg to 20 mg daily. No adverse events were observed since the introduction of the second biologic. CONCLUSION: Our experience indicates that Mepolizumab may be beneficial and safe as an add-on biologic in a patient whose allergic and eosinophilic asthma remains uncontrolled despite treatment with an anti-IgE strategy. Further studies on a larger number of patients are required to demonstrate whether the positive outcomes published so far are replicable on a larger scale.
Assuntos
Antiasmáticos , Asma , Humanos , Feminino , Idoso , Asma/tratamento farmacológico , Asma/induzido quimicamente , Qualidade de Vida , Omalizumab/uso terapêutico , Terapia BiológicaRESUMO
IgE is central to the development of allergic diseases, and its neutralization alleviates allergic symptoms. However, most of these antibodies are based on IgG1, which is associated with an increased risk of fragment crystallizable-mediated side effects. Moreover, omalizumab, an anti-IgE antibody approved for therapeutic use, has limited benefits for patients with high IgE levels. Here, we assess a fusion protein with extracellular domain of high affinity IgE receptor, FcεRIα, linked to a IgD/IgG4 hybrid Fc domain we term IgETRAP, to reduce the risk of IgG1 Fc-mediated side effects. IgETRAP shows enhanced IgE binding affinity compared to omalizumab. We also see an enhanced therapeutic effect of IgETRAP in food allergy models when combined with Bifidobacterium longum, which results in mast cell number and free IgE levels. The combination of IgETRAP and B. longum may therefore represent a potent treatment for allergic patients with high IgE levels.
Assuntos
Bifidobacterium longum , Hipersensibilidade Alimentar , Bifidobacterium longum/metabolismo , Suplementos Nutricionais , Hipersensibilidade Alimentar/terapia , Humanos , Imunoglobulina D , Imunoglobulina E , Imunoglobulina G , Omalizumab/uso terapêutico , Receptores de IgE/metabolismoRESUMO
The management of chronic rhinosinusitis with nasal polyps (CRSwNP) is challenging due to disease recurrence and adverse effects. Both surgical and medical treatment modalities impact the quality of patients' lives. Monoclonal antibody treatment has recently been used successfully in CRS with limited reported adverse events. We aimed to review the literature to shed more light on the safety and adverse events associated with the biological therapy of CRSwNP. A comprehensive systematic review was conducted on the safety of different biological treatments when used for managing CRSwNP. We have included 13 studies in the present systematic review, including 12 randomized controlled trials (RCTs) and one cross-sectional study. The total sample size for the included studies was 2282 patients. Six studies investigated the safety and adverse events of dupilumab; three investigated omalizumab, three investigated mepolizumab, and only one investigated reslizumab. Some studies have reported that adverse events were common with these types of drugs. However they were not specific and self-limited. Headaches, injection site reactions, and pharyngitis were the most common adverse events found among the reported adverse events. The Dupilumab trial reported pharyngitis in 225 patients (22.4 %) followed by erythema in 9.4 %, headache in 8.1 %, epistaxis in 5.1 %, and asthma in 1.7 % of patients. Trials which used omalizumab reported headaches, nasal pharyngitis, injection-site reactions to be the most common adverse events with estimated prevalence rates of 8.1 %, 5.9 %, and 5.2 %, respectively. Mepolizumab and reslizumab studies reported that 40 % of patients were complicated by nasal polyps/congestion/pharyngitis/infections, 14 had a headache (15.5 %), two developed asthma (2.2 %), and only one patient (1.1 %) had epistaxis as an adverse event. Although the literature's current investigations indicate the safety of the biologic treatment modalities, further studies are needed as some uncertainty among the trials have been reported.
Assuntos
Asma , Produtos Biológicos , Pólipos Nasais , Faringite , Rinite , Sinusite , Humanos , Pólipos Nasais/complicações , Pólipos Nasais/tratamento farmacológico , Rinite/complicações , Rinite/tratamento farmacológico , Omalizumab/uso terapêutico , Epistaxe/terapia , Sinusite/complicações , Sinusite/tratamento farmacológico , Doença Crônica , Terapia Biológica , Anticorpos Monoclonais/uso terapêutico , Produtos Biológicos/uso terapêutico , Cefaleia/terapia , Faringite/tratamento farmacológico , Qualidade de VidaRESUMO
INTRODUCTION: This study aimed to evaluate factors affecting drug survival and treatment response in patients with chronic urticaria treated with omalizumab in clinical practice. METHODS: This study included 386 patients with chronic urticaria. Demographic characteristics, clinical features, laboratory parameters, and omalizumab treatment data were analyzed retrospectively. The 7-day urticaria activity score (UAS7) and urticaria control test (UCT) were used to assess disease severity and treatment responses. RESULTS: Well-controlled disease (UAS7 ≤6) was achieved in 59.3% of patients at a median of 2 months. Complete response was significantly higher in patients treated with omalizumab for ≥12 months (p < 0.001). Family history of asthma (p = 0.01) was less frequent, and disease duration (p = 0.041) was shorter in patients with well-controlled disease. Total treatment duration was longer in patients with relapse (p < 0.001) and serum Helicobacter pylori IgA positivity (p = 0.029). DISCUSSION/CONCLUSION: Treatment response is better in patients treated with omalizumab for ≥12 months. However, prolonged treatment does not prevent relapse. Our findings suggest that continuous or intermittent therapy is an appropriate alternative treatment option in patients with severe chronic urticaria; however, continuous therapy can be preferred to maintain the patient's quality of life.
Assuntos
Antialérgicos , Urticária Crônica , Urticária , Humanos , Omalizumab/uso terapêutico , Omalizumab/efeitos adversos , Urticária Crônica/tratamento farmacológico , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Urticária/tratamento farmacológico , Doença Crônica , RecidivaRESUMO
Background and aim It is still unclear whether patients with severe asthma are at greater risk of developing severe COVID-19, particularly pediatric allergic patients under biologic therapy. Studies targeting pediatric patients are currently limited; thus, this study aims to assess the clinical characteristics of young patients with severe asthma under biological therapies during the COVID-19 pandemic. Methods We collected data from February 2020 to April 2021. Patients with severe asthma treated with biological therapies (omalizumab and mepolizumab) have been enrolled. We described demographic data, clinical features, therapies, comorbidities, and laboratory findings for each patient. For patients who got COVID-19, we also described the severity of the disease, the need for hospitalization, and specific therapy. Results A total of 14 patients were included in the study, 11 (78.6%) of them under treatment with omalizumab and 3 (21.6%) with mepolizumab. We identified four patients (28.6%) who tested positive for SARS-CoV-2. Two patients treated with mepolizumab had an asymptomatic disease, and two patients treated with omalizumab had mild disease. Only one patient with mild COVID-19 required hospitalization and specific therapy because of severe obesity. Conclusions No differences regarding the SARS-CoV-2 infection have been found between the two treatments groups. Furthermore, any poor outcome has been observed, confirming the safety of biological therapies. The limited number of patients enrolled and the lack of a control group did not establish a significant risk for infections for these patients.
Assuntos
Antiasmáticos , Asma , COVID-19 , Adolescente , Antiasmáticos/efeitos adversos , Asma/tratamento farmacológico , Terapia Biológica/efeitos adversos , Criança , Humanos , Omalizumab/uso terapêutico , Pandemias , SARS-CoV-2RESUMO
A alergia ocular, também conhecida como conjuntivite alérgica (CA), é uma reação de hipersensibilidade mediada por imunoglobulina E (IgE) do olho desencadeada por aeroalérgenos, principalmente ácaros da poeira doméstica e pólen de gramíneas. Os sintomas geralmente consistem em prurido ocular ou periocular, lacrimejamento e olhos vermelhos que podem estar presentes durante todo o ano ou sazonalmente. A alergia ocular tem frequência elevada, é subdiagnosticada e pode ser debilitante para o paciente. É potencialmente danosa para a visão, nos casos em que ocasiona cicatrização corneana grave, e na maioria dos pacientes associa-se a outros quadros alérgicos, principalmente rinite, asma e dermatite atópica. É classificada em conjuntivite alérgica perene, conjuntivite alérgica sazonal, ceratoconjuntivite atópica e ceratoconjuntivite vernal. O diagnóstico procura evidenciar o agente etiológico e a confirmação se dá pela realização do teste de provocação conjuntival. O tratamento baseia-se em evitar o contato com os desencadeantes, lubrificação, anti-histamínicos tópicos, estabilizadores de mastócitos, imunossupressores e imunoterapia específica com o objetivo de obter o controle e prevenir as complicações da doença.
Ocular allergy, also known as allergic conjunctivitis, is an immunoglobulin E-mediated hypersensitivity reaction of the eye triggered by airborne allergens, primarily house dust mites and grass pollen. Symptoms usually consist of ocular or periocular itching, watery eyes, and red eyes that may be present year-round or seasonally. Ocular allergy has a high frequency, is underdiagnosed, and can be debilitating for the patient. It is potentially harmful to vision in cases of severe corneal scarring, and in most patients, it is associated with other allergic conditions, especially rhinitis, asthma, and atopic dermatitis. It is classified as perennial allergic conjunctivitis, seasonal allergic conjunctivitis, atopic keratoconjunctivitis, and vernal keratoconjunctivitis. Diagnosis seeks to identify the etiologic agent, and confirmation is given by conjunctival provocation testing. Treatment is based on avoiding contact with triggers, lubrication, topical antihistamines, mast cell stabilizers, immunosuppressants, and specific immunotherapy with the aim of achieving control and preventing disease complications.