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JAMA Dermatology Jan 2019Omalizumab is indicated for the management of chronic idiopathic urticaria (CIU) (also known as chronic spontaneous urticaria) in adolescents and adults with persistent... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Omalizumab is indicated for the management of chronic idiopathic urticaria (CIU) (also known as chronic spontaneous urticaria) in adolescents and adults with persistent hives not controlled with antihistamines. The effectiveness of omalizumab in the real-world management of CIU is largely unknown.
OBJECTIVE
To quantitatively synthesize what is known about the benefits and harms of omalizumab in the real-world clinical management of CIU regarding urticaria activity, treatment response, and adverse events.
DATA SOURCES
Published observational studies (January 1, 2006, to January 1, 2018) and scientific abstracts on the effectiveness of omalizumab in CIU were identified using PubMed, Embase, Web of Science, and Cochrane search engines; references were searched to identify additional studies.
STUDY SELECTION
Included studies were observational in design and included at least 1 outcome in common with other studies and at a concurrent time point of exposure to omalizumab. A total of 67 articles (35.2% of those screened) were included in the analysis.
DATA EXTRACTION AND SYNTHESIS
PRISMA and MOOSE guidelines were followed; independent selection and data extraction were completed by 2 observers. Random-effects meta-analyses were performed.
MAIN OUTCOMES AND MEASURES
Main outcomes were change in weekly Urticaria Activity Score (UAS7; range, 0-42), change in Urticaria Activity Score (UAS; range 0-6) (higher score indicating worse outcome in both scales), complete and partial response rates (percentages), and adverse event rate (percentage).
RESULTS
Omalizumab therapy was associated with an improvement in UAS7 scores (-25.6 points, 95% CI, -28.2 to -23.0; P < .001; 15 studies, 294 patients), an improvement in UAS scores (-4.7 points, 95% CI, -5.0 to -4.4, P < .001; 10 studies, 1158 patients), an average complete response rate of 72.2% (95% CI, 66.1%-78.3%; P < .001; 45 studies, 1158 patients) with an additional average partial response rate of 17.8% (95% CI, 11.7%-23.9%; P < .001; 37 studies, 908 patients), and an average adverse event rate of 4.0% (95% CI, 1.0%-7.0%; P < .001; any level of severity, 47 studies, 1314 patients).
CONCLUSIONS AND RELEVANCE
Benefits and safety of omalizumab in the real-world treatment of CIU meet or exceed results gleaned from clinical trials. These real-world data on omalizumab in CIU may help inform both clinical treatment expectations and policy decision making.
Topics: Adolescent; Adult; Anti-Allergic Agents; Chronic Disease; Humans; Omalizumab; Remission Induction; Treatment Outcome; Urticaria
PubMed: 30427977
DOI: 10.1001/jamadermatol.2018.3447 -
Journal of Investigational Allergology... 2017Food allergy is a potentially life-threatening condition with no approved therapies apart from avoidance and injectable epinephrine for treatment of acute allergic... (Review)
Review
Food allergy is a potentially life-threatening condition with no approved therapies apart from avoidance and injectable epinephrine for treatment of acute allergic reactions. Oral immunotherapy (OIT) is an experimental treatment in which patients consume gradually increasing quantities of the food to which they are allergic in an attempt to induce some level of desensitization. While desensitization is possible in most patients, OIT carries significant risks for allergic reactions, and the ability to induce longer-term tolerance has not yet been established. This review focuses on selected studies of OIT for the treatment of common food allergies such as cow's milk, hen's egg, and peanut.
Topics: Anti-Allergic Agents; Desensitization, Immunologic; Egg Hypersensitivity; Food Hypersensitivity; Humans; Milk Hypersensitivity; Omalizumab; Peanut Hypersensitivity; Sublingual Immunotherapy
PubMed: 28102823
DOI: 10.18176/jiaci.0143 -
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 -
American Family Physician Jun 2017Urticaria commonly presents with intensely pruritic wheals, sometimes with edema of the subcutaneous or interstitial tissue. It has a lifetime prevalence of about 20%.... (Review)
Review
Urticaria commonly presents with intensely pruritic wheals, sometimes with edema of the subcutaneous or interstitial tissue. It has a lifetime prevalence of about 20%. Although often self-limited and benign, it can cause significant discomfort, continue for months to years, and uncommonly represent a serious systemic disease or life-threatening allergic reaction. Urticaria is caused by immunoglobulin E- and non-immunoglobulin E-mediated release of histamine and other inflammatory mediators from mast cells and basophils. Diagnosis is made clinically; anaphylaxis must be ruled out. Chronic urticaria is idiopathic in 80% to 90% of cases. Only a limited nonspecific laboratory workup should be considered unless elements of the history or physical examination suggest specific underlying conditions. The mainstay of treatment is avoidance of triggers, if identified. The first-line pharmacotherapy is second-generation H1 antihistamines, which can be titrated to greater than standard doses. First-generation H1 antihistamines, H2 antihistamines, leukotriene receptor antagonists, high-potency antihistamines, and brief corticosteroid bursts may be used as adjunctive treatment. In refractory chronic urticaria, patients can be referred to subspecialists for additional treatments, such as omalizumab or cyclosporine. More than one-half of patients with chronic urticaria will have resolution or improvement of symptoms within a year.
Topics: Cyclosporine; Dermatologic Agents; Diagnosis, Differential; Histamine H1 Antagonists; Humans; Omalizumab; Urticaria
PubMed: 28671445
DOI: No ID Found -
Respirology (Carlton, Vic.) Aug 2023Type 2 (T2) innate lymphoid cells (ILC2s) contribute to airway inflammation and disease in asthma. We hypothesize that ILC2s isolated from people with severe allergic...
BACKGROUND AND OBJECTIVE
Type 2 (T2) innate lymphoid cells (ILC2s) contribute to airway inflammation and disease in asthma. We hypothesize that ILC2s isolated from people with severe allergic and eosinophilic asthma would exhibit an enhanced T2 inflammatory activity that would be altered following treatment with mepolizumab and omalizumab. We compare peripheral blood (PB) isolated ILC2's proliferative capacity, IL-5 and IL-13 secretion and phenotype between healthy without asthma (HC), non-asthma allergic (NAA), mild asthma (MA) and severe allergic and eosinophilic asthma (SA) subjects. We then determined the impact of 6 months treatment with either mepolizumab or omalizumab on ILC2s physiology of SA subjects.
METHODS
ILC2s were sorted and cultured in the presence of IL-2, IL-25, IL-33 and thymic stromal lymphopoietin (TSLP) for 14 days. ILC2s proliferation, phenotypes and functions were assessed using flowcytometry. The ILC2s response was then reassessed following clinically successful treatment of SA subjects with mepolizumab and omalizumab.
RESULTS
SA ILC2s demonstrated increased proliferative capacity, TSLP receptor (TSLPR), GATA3 and NFATc1 protein expressions and increased IL-5 and IL-13 release. ILC2s were also capable of releasing IL-6 in response to stimulation. Mepolizumab treatment reduced ILC2s proliferative capacity and expression of TSLPR, GATA3 and NFATc1. Both mepolizumab and omalizumab were associated with reduced ILC2s release of IL-5 and IL-13, only mepolizumab reduced IL-6.
CONCLUSION
ILC2s from severe allergic and eosinophilic asthma demonstrated an active phenotype typified by increased proliferation, TSLPR, GATA3 and NFATc1 expression and increased IL-5, IL-13 and IL-6 release. Mepolizumab reduced markers of ILC2s activation.
Topics: Humans; Immunity, Innate; Interleukin-13; Biological Products; Omalizumab; Interleukin-5; Interleukin-6; Lymphocytes; Asthma; Cytokines; Pulmonary Eosinophilia; Cell Proliferation
PubMed: 37114915
DOI: 10.1111/resp.14506 -
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 -
Recent Patents on Inflammation &... 2019Up to 1% of the general population in the USA and Europe suffer from chronic urticaria (CU) at some point in their lifetime. CU has an adverse effect on the quality of... (Review)
Review
BACKGROUND
Up to 1% of the general population in the USA and Europe suffer from chronic urticaria (CU) at some point in their lifetime. CU has an adverse effect on the quality of life.
OBJECTIVE
This study aims to provide an update on the epidemiology, pathogenesis, clinical manifestations, diagnosis, aggravating factors, complications, treatment and prognosis of CU.
METHODS
The search strategy included meta-analyses, randomized controlled trials, clinical trials, reviews and pertinent references. Patents were searched using the key term "chronic urticaria" at the following links: www.google.com/patents, www.uspto.gov, and www.freepatentsonline.com.
RESULTS
CU is a clinical diagnosis, based on the episodic appearance of characteristic urticarial lesions that wax and wane rapidly, with or without angioedema, on most days of the week, for a period of six weeks or longer. Triggers such as medications, physical stimuli, and stress can be identified in 10 to 20% of cases. C-reactive protein/erythrocyte sedimentation rate, and complete blood cell count with differential are the screening tests that may be used to rule out an underlying disorder. The mainstay of therapy is reassurance, patient education, avoidance of known triggers, and pharmacotherapy. Secondgeneration H1 antihistamines are the drugs of choice for initial therapy because of their safety and efficacy profile. If satisfactory improvement does not occur after 2 to 4 weeks or earlier if the symptoms are intolerable, the dose of second-generation H1 antihistamines can be increased up to fourfold the manufacturer's recommended dose (all be it off license). If satisfactory improvement does not occur after 2 to 4 weeks or earlier if the symptoms are intolerable after the fourfold increase in the dosage of second-generation H1 antihistamines, omalizumab should be added. If satisfactory improvement does not occur after 6 months or earlier if the symptoms are intolerable after omalizumab has been added, treatment with cyclosporine and second-generation H1 antihistamines is recommended. Short-term use of systemic corticosteroids may be considered for acute exacerbation of CU and in refractory cases. Recent patents for the management of chronic urticaria are also discussed. Complications of CU may include skin excoriations, adverse effect on quality of life, anxiety, depression, and considerable humanistic and economic impacts. On average, the duration of CU is around two to five years. Disease severity has an association with disease duration.
CONCLUSION
CU is idiopathic in the majority of cases. On average, the duration of CU is around two to five years. Treatment is primarily symptomatic with second generation antihistamines being the first line. Omalizumab has been a remarkable advancement in the management of CU and improves the quality of life beyond symptom control.
Topics: Adrenal Cortex Hormones; Angioedema; Animals; Blood Cell Count; Blood Sedimentation; C-Reactive Protein; Chronic Urticaria; Cyclosporine; Histamine H1 Antagonists, Non-Sedating; Humans; Immunologic Factors; Omalizumab; Pruritus; Quality of Life; Vasculitis
PubMed: 30924425
DOI: 10.2174/1872213X13666190328164931 -
The Journal of Allergy and Clinical... Apr 2022Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear. (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: A systematic review and network meta-analysis.
BACKGROUND
Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear.
OBJECTIVE
We compared the effects of mAbs and aspirin desensitization (ASA-D) for treatment of CRSwNP.
METHODS
We searched the Medline, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, US Food and Drug Administration, and the European Medicines Agency databases from inception to August 4, 2021, for randomized controlled trials comparing the effects of mAbs and ASA-D for CRSwNP. We conducted network meta-analysis of sinusitis symptoms, heath-related quality of life, rescue oral corticosteroids and surgery, endoscopic and radiologic scores, and adverse events. We used the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach to assess certainty of evidence. PROSPERO CRD42020177334.
RESULTS
Twenty-nine randomized controlled trials evaluating 8 treatments (n = 3461) were included in the network meta-analysis. Compared to placebo, moderate to high certainty evidence showed that health-related quality of life (SNOT-22) improved with dupilumab (mean difference [MD] -19.91 [95% confidence interval (CI) -22.50, -17.32]), omalizumab (MD -16.09 [95% CI -19.88, -12.30]), mepolizumab (MD -12.89 [95% CI -16.58, -9.19], ASA-D (MD -10.61 [95% CI -14.51, -6.71]), and benralizumab (MD -7.68 [95% CI -12.09, -3.27]). The risk of rescue nasal polyp surgery likely decreased with dupilumab (risk difference [RD] -16.35% [95% CI -18.13, -13.48]), omalizumab (RD -7.40% [95% CI -11.04, -2.43]), mepolizumab (RD -12.33% [95% CI -15.56, -7.22]), and ASA-D (RD -16.00% [95% CI -19.79, 0.21]; all moderate certainty). Comparisons among agents show with moderate to high certainty that dupilumab ranks among the most beneficial for 7 of 7 outcomes, omalizumab for 2 of 7, mepolizumab for 1 of 7, and ASA-D for 1 of 7.
CONCLUSIONS
Multiple biologics and ASA-D credibly improve patient-important outcomes, with clinically important differences in effects among agents; dupilumab uniquely ranks among the most beneficial for all outcomes studied.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Aspirin; Chronic Disease; Humans; Nasal Polyps; Network Meta-Analysis; Omalizumab; Quality of Life; Sinusitis
PubMed: 34543652
DOI: 10.1016/j.jaci.2021.09.009 -
International Forum of Allergy &... Feb 2023Comparative effectiveness research between endoscopic sinus surgery (ESS) and biologic therapy for severe chronic rhinosinusitis with nasal polyposis (CRSwNP) is a...
BACKGROUND
Comparative effectiveness research between endoscopic sinus surgery (ESS) and biologic therapy for severe chronic rhinosinusitis with nasal polyposis (CRSwNP) is a nascent field as new therapeutic modalities become clinically available.
METHODS
A prospective, multicenter cohort of CRSwNP patients, undergoing ESS between 2011 and 2019, were compared to phase-3 biologic trial data. Patients undergoing ESS received baseline nasal endoscopy quantified via Lund-Kennedy (LK) grading. Patients meeting inclusion criteria, modified from Dupilumab-LIBERTY-NP-24&52, omalizumab-POLYP-1&2, and Mepolizumab-SYNAPSE clinical trials, were included in this study. Baseline characteristics and outcome measures were compared between these cohorts at 24 weeks and 52 weeks, when possible.
RESULTS
A total of 111 CRSwNP patients met modified inclusion criteria. There were no statistically significant differences in baseline age, sex, asthma status, aspirin-exacerbated respiratory disease status, smell identification, LK-polyp score, and Lund-Mackay computed tomography (CT) scores between ESS and biologic groups. At 24 weeks, ESS demonstrated significantly greater improvements in 22-item Sino-Nasal Outcome Test (SNOT-22) compared to one (of two) dupilumab trials (p < 0.05) and both omalizumab trials (p < 0.001). ESS associated with significantly lower nasal polyp scores (NPS) compared to dupilumab (p < 0.001) and omalizumab (p < 0.001), despite comparable improvements in smell identification (p > 0.05). At 52 weeks, ESS resulted in statistically similar improvement in SNOT-22 scores compared to dupilumab (p = 0.21), but NPS remained significantly lower in the ESS group compared to dupilumab (p < 0.001) and mepolizumab (p < 0.001).
CONCLUSION
At 24 weeks and 52 weeks, ESS offers comparable SNOT-22 improvements compared to dupilumab. ESS and dupilumab offer comparable improvement in smell identification at 24 weeks. Compared to omalizumab, ESS offers superior SNOT-22 improvements. ESS offers significantly greater reductions in polyp size compared to omalizumab, dupilumab, and mepolizumab therapies.
Topics: Humans; Nasal Polyps; Prospective Studies; Omalizumab; Rhinitis; Sinusitis; Biological Products; Endoscopy; Chronic Disease; Treatment Outcome
PubMed: 35980852
DOI: 10.1002/alr.23059