-
International Journal of Molecular... May 2023Currently, three classes of monoclonal antibodies targeting type 2 inflammation pathways are available in Italy for the treatment of severe asthma: anti-IgE... (Review)
Review
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.
Topics: Humans; Omalizumab; Asthma; Antibodies, Monoclonal; Biological Therapy; Eosinophils; Anti-Asthmatic Agents
PubMed: 37298514
DOI: 10.3390/ijms24119563 -
Handbook of Experimental Pharmacology 2022Wheals and angioedema are the signature signs of urticaria, and itch is the key symptom. Urticaria, in most patients, is acute and resolves within days (acute urticaria,...
Wheals and angioedema are the signature signs of urticaria, and itch is the key symptom. Urticaria, in most patients, is acute and resolves within days (acute urticaria, AU). Chronic urticaria (CU) can be of long duration and results not only in severely impaired quality of life but also has a socioeconomic impact due to work productivity impairment. In some patients with CU, the wheals and angioedema are induced exclusively by defined and definite triggers (chronic inducible urticaria, CIndU). In most patients with CU, wheals and angioedema develop unprompted, spontaneously (chronic spontaneous urticaria, CSU). The management of CU aims for the complete control and absence of its signs and symptoms. This is achieved, in most patients, by prophylactic treatment until spontaneous remission occurs. Modern, second-generation H1-antihistamines are the first-line therapy, with the option of updosing to fourfold, and omalizumab is used when this fails.
Topics: Anti-Allergic Agents; Chronic Disease; Chronic Urticaria; Humans; Omalizumab; Quality of Life; Urticaria
PubMed: 34247278
DOI: 10.1007/164_2021_506 -
The Journal of Allergy and Clinical... Mar 2021Guidelines for the treatment of chronic spontaneous urticaria (CSU) recommend the use of the IgE-targeted biologic omalizumab in patients with antihistamine-refractory... (Review)
Review
Guidelines for the treatment of chronic spontaneous urticaria (CSU) recommend the use of the IgE-targeted biologic omalizumab in patients with antihistamine-refractory disease. The rationale for this is supported by the key role of IgE and its high-affinity receptor, FcεRI, in the degranulation of skin mast cells that drives the development of the signs and symptoms of CSU, itchy wheals, and angioedema. Here, we review the current understanding of the pathogenesis of CSU and its autoimmune endotypes. We describe the mechanisms of action of omalizumab, the only biologic currently approved for CSU, its efficacy and ways to improve it, biomarkers for treatment response, and strategies for its discontinuation. We provide information on the effects of the off-label use, in CSU, of biologics licensed for the treatment of other diseases, including dupilumab, benralizumab, mepolizumab, reslizumab, and secukinumab. Finally, we discuss targets for novel biologics and where we stand with their clinical development. These include IgE/ligelizumab, IgE/GI-310, thymic stromal lymphopoietin/tezepelumab, C5a receptor/avdoralimab, sialic acid-binding Ig-like lectin 8/lirentelimab, CD200R/LY3454738, and KIT/CDX-0159. Our aim is to provide updated information and guidance on the use of biologics in the treatment of patients with CSU, now and in the near future.
Topics: Anti-Allergic Agents; Biological Products; Chronic Disease; Chronic Urticaria; Humans; Omalizumab; Urticaria
PubMed: 33685605
DOI: 10.1016/j.jaip.2020.11.043 -
Clinical Reviews in Allergy & Immunology Aug 2020Chronic spontaneous urticaria (CSU) is defined as the spontaneous development of itchy hives and/or angioedema due to known or unknown causes that last for at least... (Review)
Review
Chronic spontaneous urticaria (CSU) is defined as the spontaneous development of itchy hives and/or angioedema due to known or unknown causes that last for at least 6 weeks. At any given time, CSU is believed to affect 0.5-1% of the global population. Omalizumab (a recombinant, humanized anti-immunoglobulin-E antibody) is the only approved treatment for antihistamine refractory CSU. However, ~ 30% of patients remain symptomatic at licensed doses of omalizumab 150 mg and 300 mg, even after a treatment period of over 6 months. In the recent years, there have been several studies on updosing of the drug, suggesting that the individualized approach for urticaria treatment with omalizumab is useful. In this article, we provide an overview of these studies and the real-world data on omalizumab updosing as it became necessary to obtain complete CSU symptom control in a proportion of patients. Published observational studies (from June 2003 to October 2019) on the updosing of omalizumab in CSU were identified using PubMed and Ovid databases. Reports mainly show that updosing/dose adjustment evaluated with the assessment of disease activity (Urticaria Activity Score) and control (Urticaria Control Test) achieves better clinical response to omalizumab with a good safety profile in a pool of patients with CSU. These real-world data will provide an overview of updosing of omalizumab in CSU and aid in setting informed clinical practice treatment expectations.
Topics: Anti-Allergic Agents; Chronic Urticaria; Evidence-Based Medicine; Humans; Immunoglobulin E; Omalizumab; Precision Medicine; Treatment Outcome
PubMed: 32418171
DOI: 10.1007/s12016-020-08794-6 -
The Journal of Allergy and Clinical... Dec 2022The high prevalence of atopic diseases in women of childbearing age reveals the need to determine the safety of biologics during pregnancy. This review summarizes the... (Review)
Review
The high prevalence of atopic diseases in women of childbearing age reveals the need to determine the safety of biologics during pregnancy. This review summarizes the effects of 7 Food and Drug Administration-approved biologics (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab, and tralokinumab) on maternal and fetal outcomes. For this purpose, we reviewed English-language publications to investigate whether the use of biologics for atopic diseases during pregnancy increased the risk of preterm delivery, stillbirth, low birth weight, or congenital malformations. Most publications found were case reports, case series, or observational studies reporting outcomes in a total of 313 pregnancies. No randomized controlled studies were identified. We found that biologics do not seem to influence maternal or fetal outcomes. Indeed, worsening of the underlying atopic disease during pregnancy appears to be more detrimental to the viability of the pregnancy. Given the small sample size and scarcity of studies, future research should include prospective studies with comparable control groups without exposure to biologics and multicenter registries for long-term follow-up.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Biological Products; Asthma; Prospective Studies; Omalizumab; Anti-Asthmatic Agents; Multicenter Studies as Topic
PubMed: 35987486
DOI: 10.1016/j.jaip.2022.08.013 -
Allergy Apr 2021Cold urticaria (ColdU) is a common form of chronic inducible urticaria characterized by the development of wheals, angioedema or both in response to cold exposure.... (Review)
Review
Cold urticaria (ColdU) is a common form of chronic inducible urticaria characterized by the development of wheals, angioedema or both in response to cold exposure. Recent research and guideline updates have advanced our understanding and management of ColdU. Today, its pathophysiology is thought to involve the cold-induced formation of autoallergens and IgE to these autoallergens, which provoke a release of proinflammatory mediators from skin mast cells. The classification of ColdU includes typical and atypical subtypes. We know that cold-induced wheals usually develop on rewarming and resolve within an hour and that anaphylaxis can occur. The diagnosis relies on the patient's history and cold stimulation testing. Additional diagnostic work-up, including a search for underlying infections, should only be done if indicated by the patient's history. The management of ColdU includes cold avoidance, the regular use of nonsedating antihistamines and the off-label use of omalizumab. However, many questions regarding ColdU remain unanswered. Here, we review what is known about ColdU, and we present important unanswered questions on the epidemiology, underlying pathomechanisms, clinical heterogeneity and treatment outcomes. Our aim is to guide future efforts that will close these knowledge gaps and advance the management of ColdU.
Topics: Angioedema; Chronic Urticaria; Cold Temperature; Histamine H1 Antagonists, Non-Sedating; Humans; Omalizumab; Urticaria
PubMed: 33249577
DOI: 10.1111/all.14674 -
International Archives of Allergy and... 2022Compared with the placebo, biologics are beneficial in reducing nasal polyp mass and safe in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Compared with the placebo, biologics are beneficial in reducing nasal polyp mass and safe in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, there lacks a head-to-head randomized trial comparing biologics. We aimed to determine the best biologic for CRSwNP.
METHODS
We performed a systematic review and network meta-analysis (NMA), which was registered with PROSPERO (No. CRD42021226766). A comprehensive search was performed in PubMed, Embase, Web of Science, and the Cochrane Library on December 29, 2020. Only randomized controlled trials (RCTs) assessing biologics in adult patients for CRSwNP were included.
RESULTS
Nine RCTs with 1,190 patients comparing 3 different biologics (dupilumab, omalizumab, and mepolizumab) and the placebo were included. Dupilumab had the best efficacy in terms of nasal polyp score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22) score, University of Pennsylvania Smell Identification Test (UPSIT) score, and nasal congestion score (NCS) for surface under the cumulative ranking curve (SUCRA) values of 0.900, 0.916, 1.000, and 0.807, respectively. Omalizumab ranked second in efficacy in terms of SNOT-22, UPSIT, and NCS for SUCRA values of 0.606, 0.500, and 0.693, respectively. Mepolizumab ranked second in efficacy in terms of NPS for SUCRA values of 0.563 and had the highest risk of adverse events (AEs) for SUCRA values of 0.746.
CONCLUSION
This is the first NMA that compared different biologics in patients with CRSwNP. Based on the efficacy (NPS) and safety (AEs), dupilumab is the best choice and omalizumab is the second best option for CRSwNP. Although mepolizumab ranked second in efficacy, it had the highest risk of AEs.
Topics: Adult; Antibodies, Monoclonal, Humanized; Biological Products; Chronic Disease; Humans; Nasal Polyps; Network Meta-Analysis; Omalizumab; Rhinitis; Sinusitis
PubMed: 34607329
DOI: 10.1159/000519228 -
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 clinical benefit of mepolizumab replacing omalizumab in uncontrolled severe eosinophilic asthma.Allergy Sep 2019Mepolizumab and omalizumab are treatments for distinct but overlapping severe asthma phenotypes. (Clinical Trial)
Clinical Trial
BACKGROUND
Mepolizumab and omalizumab are treatments for distinct but overlapping severe asthma phenotypes.
OBJECTIVE
To assess if patients eligible for both biologics but not optimally controlled with omalizumab experience improved asthma control when switched directly to mepolizumab.
METHODS
OSMO was a multicenter, open-label, single-arm, 32-week trial in patients with ≥2 asthma exacerbations in the year prior to enrollment, despite receiving high-dose inhaled corticosteroids and other controller(s), plus omalizumab (≥4 months). At baseline, patients with blood eosinophil counts ≥150 cells/µL (or ≥300 cells/µL in the prior year) and an Asthma Control Questionnaire (ACQ)-5 score ≥1.5 discontinued omalizumab and immediately commenced mepolizumab 100 mg subcutaneously every 4 weeks. Endpoints included change from baseline in ACQ-5 score (primary), St George's Respiratory Questionnaire (SGRQ) score and the proportions of ACQ-5 and SGRQ responders, all at Week 32, and the annualized exacerbation rate over the study period.
RESULTS
At Week 32 (intent-to-treat population [n = 145]), the least squares (LS) mean changes (standard error [SE]) in ACQ-5 and SGRQ total scores were -1.45 (0.107) and -19.0 (1.64) points; with 77% and 79% of patients achieving the minimum clinically important differences (ACQ-5: ≥0.5 points; SGRQ: ≥4 points), respectively. The annualized rate of clinically significant exacerbations was 1.18 events/year, a 64% reduction from 3.26 events/year during the previous year. Safety and immunogenicity profiles were consistent with previous trials.
CONCLUSION
After directly switching from omalizumab to mepolizumab, patients with uncontrolled severe eosinophilic asthma experienced clinically significant improvements in asthma control, health status, and exacerbation rate, with no tolerability issues reported.
Topics: Adolescent; Adult; Aged; Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Child; Drug Substitution; Eosinophils; Female; Humans; Leukocyte Count; Male; Middle Aged; Omalizumab; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome; Young Adult
PubMed: 31049972
DOI: 10.1111/all.13850 -
The British Journal of Dermatology Feb 2021Chronic urticaria (CU) affects about 1% of the world population of all ages, mostly young and middle-aged women. It usually lasts for several years (> 1 year in 25-75%... (Review)
Review
Chronic urticaria (CU) affects about 1% of the world population of all ages, mostly young and middle-aged women. It usually lasts for several years (> 1 year in 25-75% of patients) and often takes > 1 year before effective management is implemented. It presents as chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU) or both in the same person. More than 25% of cases are resistant to H -antihistamines, even at higher doses, and third- and fourth-line therapies (omalizumab and ciclosporin) control the disease only in two-thirds of H -antihistamine-resistant patients. Here we review the impact of CU on different aspects of patients' quality of life and the burden of this chronic disease for the patient and society. CU may have a strong impact on health-related quality of life (HRQoL), particularly when CSU is associated with angio-oedema and/or CIndU (Dermatology Life Quality Index > 10 in 30% of patients). Comorbidities, such as anxiety and depression, which are present in more than 30% of patients with CSU, compound HRQoL impairment. Severe pruritus and the unpredictable occurrence of weals and angio-oedema are responsible for sleep disorders; sexual dysfunction; limitations on daily life, work and sports activities; interfering with life within the family and in society; and patients' performance at school and work (6% absenteeism and 25% presenteeism). Apart from treatment costs, with annual values between 900 and 2400 purchasing power parity dollars (PPP$) in Europe and the USA, CU is associated with a high consumption of medical resources and other indirect costs, which may reach a total annual cost of PPP$ 15 550.
Topics: Chronic Disease; Chronic Urticaria; Europe; Female; Humans; Middle Aged; Omalizumab; Quality of Life; Urticaria
PubMed: 32956489
DOI: 10.1111/bjd.19561