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The Journal of Allergy and Clinical... Sep 2020Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by IgE hyperproduction and eosinophilic inflammation. The anti-IgE antibody, omalizumab, has... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by IgE hyperproduction and eosinophilic inflammation. The anti-IgE antibody, omalizumab, has demonstrated efficacy in patients with CRSwNP and comorbid asthma previously.
OBJECTIVE
Our aim was to determine omalizumab safety and efficacy in CRSwNP in phase 3 trials (POLYP 1 and POLYP 2).
METHODS
Adults with CRSwNP with inadequate response to intranasal corticosteroids were randomized (1:1) to omalizumab or placebo and intranasal mometasone for 24 weeks. Coprimary end points included change from baseline to week 24 in Nasal Polyp Score (NPS) and Nasal Congestion Score. Secondary end points included change from baseline to week 24 in Sino-Nasal Outcome Test-22 (SNOT-22) score, University of Pennsylvania Smell Identification Test, sense of smell, postnasal drip, runny nose, and adverse events.
RESULTS
Patients in POLYP 1 (n = 138) and POLYP 2 (n = 127) exhibited severe CRSwNP and substantial quality of life impairment evidenced by a mean NPS higher than 6 and SNOT-22 score of approximately 60. Both studies met both the coprimary end points. SNOT-22 score, University of Pennsylvania Smell Identification Test score, sense of smell, postnasal drip, and runny nose were also significantly improved for omalizumab versus placebo. In POLYP 1 and POLYP 2, the mean changes from baseline at week 24 for omalizumab versus placebo were as follows: NPS, -1.08 versus 0.06 (P < .0001) and -0.90 versus -0.31 (P = .0140); Nasal Congestion Score, -0.89 versus -0.35 (P = .0004) and -0.70 versus -0.20 (P = .0017); and SNOT-22 score, -24.7 versus -8.6 (P < .0001) and -21.6 versus -6.6 (P < .0001). Adverse events were similar between groups.
CONCLUSION
Omalizumab significantly improved endoscopic, clinical, and patient-reported outcomes in severe CRSwNP with inadequate response to intranasal corticosteroids, and it was well tolerated.
Topics: Adrenal Cortex Hormones; Adult; Anti-Allergic Agents; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Mometasone Furoate; Nasal Polyps; Omalizumab; Rhinitis; Sinusitis; Treatment Outcome
PubMed: 32524991
DOI: 10.1016/j.jaci.2020.05.032 -
The Journal of Allergy and Clinical... May 2023Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness. (Clinical Trial)
Clinical Trial
BACKGROUND
Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness.
OBJECTIVE
Our aim was to compare the effectiveness of omalizumab, mepolizumab, and dupilumab in individuals with moderate-to-severe asthma.
METHODS
We emulated a hypothetical randomized trial using electronic health records from a large US-based academic health care system. Participants aged 18 years or older with baseline IgE levels between 30 and 700 IU/mL and peripheral eosinophil counts of at least 150 cells/μL were eligible for study inclusion. The study period extended from March 2016 to August 2021. Outcomes included the incidence of asthma-related exacerbations and change in baseline FEV value over 12 months of follow-up.
RESULTS
In all, 68 individuals receiving dupilumab, 68 receiving omalizumab, and 65 receiving mepolizumab met the inclusion criteria. Over 12 months of follow-up, 31 exacerbations occurred over 68 person years (0.46 exacerbations per person year) in the dupilumab group, 63 over 68 person years (0.93 per person year) in the omalizumab group, and 86 over 65 person years (1.32 per person year) in the mepolizumab group (adjusted incidence rate ratios: dupilumab vs mepolizumab, 0.28 [95% CI = 0.09-0.84]; dupilumab vs omalizumab, 0.36 [95% CI = 0.12-1.09]; and omalizumab vs mepolizumab, 0.78 [95% CI = 0.32-1.91]). The differences in the change in FEV comparing patients who received the different biologics were as follows: 0.11 L (95% CI = -0.003 to 0.222 L) for dupilumab versus mepolizumab, 0.082 L (95% CI -0.040 to 0.204 L) for dupilumab versus omalizumab, and 0.026 L (95% CI -0.083 to 0.140 L) for omalizumab versus mepolizumab.
CONCLUSIONS
Among patients with asthma and eosinophil counts of at least 150 cells/μL and IgE levels of 30 to 700 kU/L, dupilumab was associated with greater improvements in exacerbation and FEV value than omalizumab and mepolizumab.
Topics: Humans; Anti-Asthmatic Agents; Asthma; Immunoglobulin E; Omalizumab; Comparative Effectiveness Research
PubMed: 36740144
DOI: 10.1016/j.jaci.2023.01.020 -
Frontiers in Immunology 2022Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease of the skin. First-line treatment of systemic corticosteroids may cause serious...
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease of the skin. First-line treatment of systemic corticosteroids may cause serious adverse events. Rituximab, omalizumab, and dupilumab should be explored as alternative treatment options to improve outcomes.
OBJECTIVE
To systematically review the rituximab, omalizumab, and dupilumab treatment outcomes in bullous pemphigoid.
METHODS
A PubMed, Embase, Web of Science, and Cochrane library search were conducted on March 10, 2022. A total of 75 studies were included using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
RESULTS
Use of rituximab (n=122), omalizumab (n=53) and dupilumab (n=36) were reported in 211 patients with BP. Rituximab led to complete remission in 70.5% (n=86/122) and partial remission in 23.8% (n=29/122) of patients within 5.7 months, with a recurrence rate of 20.5% (n=25/122). 9.0% (n=11/122) of patients died and infection (6.6%, n=8/122) was the most common adverse event. Omalizumab led to complete remission in 67.9% (n=36/53) and partial remission in 20.8% (n=11/53) of patients within 6.6 months, with a recurrence rate of 5.7% (n=3/53). 1.9% (n=1/53) of patients died and thrombocytopenia (1.9%, n=1/53) was observed as the most common adverse event. Dupilumab led to complete remission in 66.7% (n=24/36) and partial remission in 19.4% (n=7/36) of patients within 4.5 months of treatment without any reported adverse events, with a recurrence rate of 5.6% (n=2/36).
CONCLUSIONS
Rituximab, omalizumab, and dupilumab have similar clinical benefits for BP patients. However, rituximab resulted in higher recurrence rates, adverse events, and mortality rates.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022316454.
Topics: Antibodies, Monoclonal, Humanized; Humans; Omalizumab; Pemphigoid, Bullous; Rituximab; Treatment Outcome
PubMed: 35769474
DOI: 10.3389/fimmu.2022.928621 -
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 -
Current Opinion in Allergy and Clinical... Jun 2021To familiarize the reader with the most recent insights in the use of Omalizumab (monoclonal anti-immunoglobulin E) monotherapy in the treatment of patients with severe... (Review)
Review
PURPOSE OF REVIEW
To familiarize the reader with the most recent insights in the use of Omalizumab (monoclonal anti-immunoglobulin E) monotherapy in the treatment of patients with severe food allergy.
RECENT FINDINGS
The current data from early stage clinical trials show that Omalizumab may be safe and effective by itself in providing desensitization to one or several foods without requiring allergen exposure.
SUMMARY
In the near future, advances in knowledge will guide the adoption and implementation of any new therapy for food allergy and allow the development of a personalized treatment tailored on the specific patient's profile.
Topics: Allergens; Antibodies, Monoclonal; Food Hypersensitivity; Humans; Immunoglobulin E; Omalizumab
PubMed: 33769312
DOI: 10.1097/ACI.0000000000000744 -
Current Opinion in Allergy and Clinical... Dec 2021To review the most relevant studies in the advancing field of omalizumab in allergen immunotherapy. (Review)
Review
PURPOSE OF REVIEW
To review the most relevant studies in the advancing field of omalizumab in allergen immunotherapy.
RECENT FINDINGS
Omalizumab has been used in combination with inhalant, venom, and food allergen immunotherapy. These studies suggest that omalizumab can decrease the time required to reach maintenance dosing and adverse events. However, severe adverse events do still occur. Limited long-term data suggests that there is a risk for increased reactivity after stopping omalizumab.
SUMMARY
Omalizumab in conjunction with immunotherapy has shown promising results for the treatment of allergic rhinitis, venom hypersensitivity, and food allergy, especially in the reduction of adverse events. Larger randomized, placebo-controlled trials are needed to better understand optimal dosing and duration, cost--benefit analysis, ideal patients, and long-term benefits. This combination therapy has the potential to improve treatment, particularly for high-risk patients.
Topics: Allergens; Desensitization, Immunologic; Food Hypersensitivity; Humans; Immunotherapy; Omalizumab; Rhinitis, Allergic; Venoms
PubMed: 34419967
DOI: 10.1097/ACI.0000000000000781 -
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 -
Current Opinion in Allergy and Clinical... Jun 2021To review the most relevant studies in the rapidly advancing field of omalizumab as an adjunct to food allergen oral immunotherapy (OIT). (Review)
Review
PURPOSE OF REVIEW
To review the most relevant studies in the rapidly advancing field of omalizumab as an adjunct to food allergen oral immunotherapy (OIT).
RECENT FINDINGS
Clinical trials have primarily focused on milk, peanut, and multiallergen OIT combined with omalizumab. These studies suggest that omalizumab in addition to OIT can decrease the time required to reach maintenance OIT dosing and adverse events; however, serious adverse events did still occur. There is limited long-term data but available information suggests that individuals are at risk for increased reactivity after stopping omalizumab, and many discontinued treatment. There has been diversity in study designs, dosing, and populations.
SUMMARY
The use of anti-IgE antibody as an adjunct to food allergen OIT has been an expanding area of research with several additional trials underway. Significant progress has been made in the past decades but further studies are needed to optimize protocols, improve safety and efficacy, and identify patients who will have the greatest benefit.
Topics: Adjuvants, Immunologic; Administration, Oral; Allergens; Desensitization, Immunologic; Food Hypersensitivity; Humans; Omalizumab
PubMed: 33605614
DOI: 10.1097/ACI.0000000000000736 -
Revue Des Maladies Respiratoires Feb 2017Omalizumab is used as a treatment for severe allergic asthma. Its intended mechanism of action is based on its anti-IgE proprieties. However, recent studies have... (Review)
Review
INTRODUCTION
Omalizumab is used as a treatment for severe allergic asthma. Its intended mechanism of action is based on its anti-IgE proprieties. However, recent studies have highlighted other mechanisms of action.
STATE OF THE ART
Omalizumab treatment is associated with a decrease in the number of dendritic cells, T and B lymphocytes and eosinophils. This anti-inflammatory activity is characterized by a decrease in the levels of several cytokines involved in the recruitment, activation and survival of eosinophils and mastocytes, and in a Th2 orientation of the immune response. A modulation of bronchial remodeling by omalizumab has recently been shown. A decrease in the production of extracellular matrix components and in the proliferation of smooth muscle cells could be involved in this modulation. These mechanisms of action could explain in part the clinical efficiency of omalizumab in non-allergic conditions such as non-allergic asthma, non-allergic urticaria or nasal polyposis.
CONCLUSION
A precise knowledge of the mechanisms of action of omalizumab could allow the identification of biomarkers predictive of efficacy of this treatment. These could be useful tools in the phenotyping of severe asthma.
Topics: Anti-Asthmatic Agents; Antibodies, Anti-Idiotypic; Asthma; Humans; Omalizumab; Respiratory Hypersensitivity; Severity of Illness Index
PubMed: 28189435
DOI: 10.1016/j.rmr.2016.07.006 -
Digestive and Liver Disease : Official... Oct 2021
Topics: Aged; Anti-Asthmatic Agents; Colitis; Colon; Female; Humans; Omalizumab
PubMed: 32893174
DOI: 10.1016/j.dld.2020.08.017