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Journal of Medical Economics 2022To compare the efficacy of tezepelumab with other approved biologics indirect treatment comparisons (ITCs) in patients aged ≥ 12 years with severe uncontrolled asthma. (Meta-Analysis)
Meta-Analysis
AIMS
To compare the efficacy of tezepelumab with other approved biologics indirect treatment comparisons (ITCs) in patients aged ≥ 12 years with severe uncontrolled asthma.
MATERIALS AND METHODS
Data from randomized controlled trials (RCTs) identified from a systematic literature review were synthesized using two different ITC approaches: network meta-analysis (NMA) and simulated treatment comparison (STC). Outcomes of interest were annualized asthma exacerbation rate (AAER) and AAER for exacerbations leading to hospitalization. To address potential heterogeneity between study populations, various subgroup analyses were performed for the NMA (based on blood eosinophil count, fractional exhaled nitric oxide level, and presence of allergic asthma), and for the STC, models were adjusted for potential treatment effect modifiers. Sensitivity analyses were performed to assess the impact of study design (exclusion of non-placebo-controlled studies and non-phase 3 or 4 studies). Results were reported as rate ratios (RRs) with 95% credible/confidence intervals and ranking statistics were computed for the NMAs.
RESULTS
Sixteen RCTs were included in at least one of the ITCs. All biologics (tezepelumab, dupilumab, benralizumab, mepolizumab, reslizumab, and omalizumab) had similar efficacy, with no statistically significant RRs for either exacerbation outcome; however, tezepelumab was favorably associated with numerically lower AAERs and was ranked first in the network for both types of exacerbation outcome. This trend was consistent in the subgroup and sensitivity analyses. As with the primary NMA, the STC results did not demonstrate any significant differences between biologics, but point estimates were favorable towards tezepelumab.
LIMITATIONS
Heterogeneity between trials was observed among eligibility criteria and clinically important patient characteristics; however, the impact on findings is expected to be low, based on consistency across analyses.
CONCLUSIONS
Findings from both ITCs (NMA and STC) support the use of tezepelumab in a broad patient population of severe uncontrolled asthma of any phenotype.
Topics: Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Biological Products; Eosinophils; Humans; Omalizumab
PubMed: 35570578
DOI: 10.1080/13696998.2022.2074195 -
International Forum of Allergy &... Jan 2024The heterogeneity of existing studies, along with the fact that there are no published head-to-head trials, are the main reasons for the lack of guidelines regarding the... (Review)
Review
Chronic rhinosinusitis with nasal polyps (CRSwNP) treated with omalizumab, dupilumab, or mepolizumab: A systematic review of the current knowledge towards an attempt to compare agents' efficacy.
BACKGROUND
The heterogeneity of existing studies, along with the fact that there are no published head-to-head trials, are the main reasons for the lack of guidelines regarding the selection of the proper biologic in treatment of chronic rhinosinusitis (CRS) with nasal polyps. The aim of this study is to summarize the current knowledge regarding the efficacy of omalizumab, dupilumab, and mepolizumab in CRS treatment. We also attempt to proceed to an indirect comparison of the agents and try to answer the tricky question: which agent to select and why?
METHODS
An extensive search in English literature was conducted in PubMed/Medline, Embase, Google Scholar, and Cochrane Database/Library. Eligibility criteria included papers with full text published in English, adult population studies, clearly described intervention protocol, and documented primary and secondary outcomes.
RESULTS
The studies included numbered 37. All agents provided significant improvement in polyp size, sinuses opacification, severity of symptoms, need for surgery and systemic corticosteroids use. Analysis of available systematic reviews, meta-analyses and indirect treatment comparison studies showed that dupilumab appeared to be the most beneficial agent, in terms of primary and secondary outcomes. However, these results are of relatively low level of evidence due to several methodological limitations.
CONCLUSIONS
Although the present analysis showed a moderate supremacy of dupilumab, there is still no evidence-based answer to the question "which biologic agent is the most effective in CRS treatment?" Improved statistical methodology, head-to-head trials, and real-life studies could lead to more robust conclusions, establishing the real role of the specific biologic agents.
Topics: Adult; Humans; Nasal Polyps; Omalizumab; Rhinosinusitis; Sinusitis; Chronic Disease; Biological Products; Rhinitis; Quality of Life; Antibodies, Monoclonal, Humanized
PubMed: 37394893
DOI: 10.1002/alr.23234 -
Clinical Reviews in Allergy & Immunology Jun 2018Non-hereditary angioedema (AE) with normal C1 esterase inhibitor (C1INH) can be presumably bradykinin- or mast cell-mediated, or of unknown cause. In this systematic... (Review)
Review
Non-hereditary angioedema (AE) with normal C1 esterase inhibitor (C1INH) can be presumably bradykinin- or mast cell-mediated, or of unknown cause. In this systematic review, we searched PubMed, EMBASE, and Scopus to provide an overview of the efficacy of different treatment options for the abovementioned subtypes of refractory non-hereditary AE with or without wheals and with normal C1INH. After study selection and risk of bias assessment, 61 articles were included for data extraction and analysis. Therapies were described for angiotensin-converting enzyme inhibitor-induced AE (ACEi-AE), for idiopathic AE, and for AE with wheals. Described treatments consisted of ecallantide, icatibant, C1INH, fresh frozen plasma (FFP), tranexamic acid (TA), and omalizumab. Additionally, individual studies for anti-vitamin K, progestin, and methotrexate were found. Safety information was available in 26 articles. Most therapies were used off-label and in few patients. There is a need for additional studies with a high level of evidence. In conclusion, in acute attacks of ACEi-AE and idiopathic AE, treatment with icatibant, C1INH, TA, and FFP often leads to symptom relief within 2 h, with limited side effects. For prophylactic treatment of idiopathic AE and AE with wheals, omalizumab, TA, and C1INH were effective and safe in the majority of patients.
Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Humans; Omalizumab; Progestins; Tranexamic Acid; Treatment Outcome
PubMed: 27672078
DOI: 10.1007/s12016-016-8585-0 -
Systematic Reviews Nov 2015Several options are available for the treatment of chronic rhinosinusitis (CRS), but disease control remains elusive for many patients. Recently, literature has emerged... (Review)
Review
BACKGROUND
Several options are available for the treatment of chronic rhinosinusitis (CRS), but disease control remains elusive for many patients. Recently, literature has emerged describing anti-IgE monoclonal antibody as a potential therapy for CRS. However, its effectiveness and safety are not well known. The purpose of this systematic review was to assess the effectiveness and safety of anti-IgE therapy and to identify evidence gaps that will guide future research for the management of CRS.
METHODS
Methodology was registered with PROSPERO (No. CRD42014007600). A comprehensive search was performed of standard bibliographic databases, Google Scholar, and clinical trials registries. Only randomized controlled trials assessing anti-IgE therapy in adult patients for the treatment of CRS were included. Two independent reviewers extracted data using a pre-defined extraction form and performed quality assessment using the Cochrane risk of bias tool and the GRADE framework.
RESULTS
Two studies met our inclusion criteria. When comparing anti-IgE therapy to placebo, there was a significant difference in Lund-McKay score (p = 0.04) while no difference was seen for percent opacification on computed tomography (CT). At 16 weeks, treatment led to a decrease in clinical polyp score. No significant difference was seen with regard to quality of life (Total Nasal Symptom Severity (TNSS), p < 0.21; Sinonasal Outcome Test 20 (SNOT-20), p < 0.60), and no serious complications were reported in either trial. Based on the quality assessment, studies were deemed to be of moderate risk of bias and a low overall quality of evidence.
CONCLUSIONS
There is currently insufficient evidence to determine the effectiveness of anti-IgE monoclonal antibody therapy for the treatment of CRS.
Topics: Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Chronic Disease; Follow-Up Studies; Humans; Randomized Controlled Trials as Topic; Rhinitis; Sinusitis; Treatment Outcome
PubMed: 26581392
DOI: 10.1186/s13643-015-0157-5 -
The Annals of Otology, Rhinology, and... Nov 2017To determine the role of biologic therapy on sinonasal symptoms and objective outcomes in chronic rhinosinusitis with nasal polyposis (CRSwNP). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the role of biologic therapy on sinonasal symptoms and objective outcomes in chronic rhinosinusitis with nasal polyposis (CRSwNP).
METHODS
PubMed, OVID MEDLINE, and Cochrane Central were reviewed from 2000 to 2015. Inclusion criteria included English-language studies containing original data on biologic therapy in CRSwNP patients with reported outcome measures. Two investigators independently reviewed all manuscripts and performed quality assessment and quantitative meta-analysis using validated tools.
RESULTS
Of 495 abstracts identified, 7 studies fulfilled eligibility: 4 randomized control trials (RCT), 1 case-control, and 2 case series. Outcome measures included nasal polyp score (NPS,6), computer tomography score (5), and symptom scores (5). Meta-analysis was performed on 5 studies: Anti-IL5 therapy (mepolizumab/reslizumab) and anti-IgE therapy (omalizumab) demonstrated a standard mean difference of NPS improvement of -0.66 (95% CI, -1.24 to -0.08) and -0.75 (95% CI, -1.93 to 0.44), respectively, between biologic therapy and placebo. Quality assessment indicated a low to moderate risk of bias for the RCTs.
CONCLUSION
Biologic therapies may prove beneficial in the treatment of recalcitrant nasal polyposis in select populations. In meta-analysis, anti-IL5 therapy demonstrates a reduction in nasal polyp score. Anti-IgE therapy reduces nasal polyp score in patients with severe comorbid asthma. Additional high-level evidence is needed to assess clinical efficacy.
Topics: Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Humans; Immunoglobulin E; Interleukin-5; Nasal Polyps; Omalizumab; Rhinitis; Sinusitis
PubMed: 28918644
DOI: 10.1177/0003489417731782 -
The Cochrane Database of Systematic... Sep 2021Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung... (Review)
Review
BACKGROUND
Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review.
OBJECTIVES
To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 09 September 2021. We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 16 August 2021.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager.
MAIN RESULTS
Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively.
AUTHORS' CONCLUSIONS
There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.
Topics: Antibodies, Anti-Idiotypic; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Cystic Fibrosis; Humans; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 34550603
DOI: 10.1002/14651858.CD010288.pub5 -
The Cochrane Database of Systematic... Mar 2018Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung... (Review)
Review
BACKGROUND
Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review.
OBJECTIVES
To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 29 September 2017.We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 24 January 2018.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager.
MAIN RESULTS
Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively.
AUTHORS' CONCLUSIONS
There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.
Topics: Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Cystic Fibrosis; Early Termination of Clinical Trials; Humans; Itraconazole; Omalizumab; Randomized Controlled Trials as Topic
PubMed: 29551015
DOI: 10.1002/14651858.CD010288.pub4 -
The Journal of Allergy and Clinical... Aug 2023Omalizumab is the only biological agent approved for patients with chronic spontaneous urticaria (CSU), but no biomarker is well established for predicting clinical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Omalizumab is the only biological agent approved for patients with chronic spontaneous urticaria (CSU), but no biomarker is well established for predicting clinical response to omalizumab.
OBJECTIVE
We aimed to determine the association between baseline total serum IgE levels and the effects of omalizumab in patients with CSU.
METHODS
PubMed, Web of Science, Scopus, and Cochrane Library were systematically searched for relevant studies from inception to August 23, 2022. The research protocol was registered on PROSPERO (CRD42022355592). No language restrictions were applied. A random-effects model was used for meta-analysis.
RESULTS
Ten interventional studies, including 1 randomized controlled trial, were included in the final meta-analysis, and a total of 866 patients with CSU were included. A pooled analysis showed significantly higher serum total IgE levels in complete responders (CRs) than in nonresponders (NRs) (mean difference [MD]: 56.509 IU/mL; 95% confidence interval [CI]: 24.230-88.789) and in partial responders (PRs) than in NRs (MD: 62.688 IU/mL; 95% CI: 32.949-92.427), but no significant difference was detected between CRs and PRs. The mean total IgE levels for CRs, PRs, and NRs were 163.154, 179.926, and 51.535 IU/mL, respectively. Further, the serum total IgE levels in early CRs were significantly higher compared with late CRs (MD: 55.194 IU/mL; 95% CI: 13.402-96.986). The sensitivity analyses with the leave-one-out method validated the robustness of all findings.
CONCLUSIONS
This systematic review and meta-analysis provide convincing evidence that pretreatment total serum IgE levels in patients with CSU are associated with clinical responses to omalizumab.
Topics: Humans; Omalizumab; Anti-Allergic Agents; Urticaria; Immunoglobulin E; Treatment Outcome; Chronic Urticaria; Chronic Disease; Randomized Controlled Trials as Topic
PubMed: 37263348
DOI: 10.1016/j.jaip.2023.05.033 -
The Cochrane Database of Systematic... Nov 2015Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung... (Review)
Review
BACKGROUND
Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review.
OBJECTIVES
To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 27 July 2015.We searched the ongoing trial registry clinicaltrials.gov for any ongoing trials. Latest search for clinicaltrials.gov: 23 October 2015.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager.
MAIN RESULTS
Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively.
AUTHORS' CONCLUSIONS
There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.
Topics: Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Cystic Fibrosis; Early Termination of Clinical Trials; Humans; Itraconazole; Omalizumab; Randomized Controlled Trials as Topic
PubMed: 26545165
DOI: 10.1002/14651858.CD010288.pub3 -
Journal of Investigational Allergology... Dec 2023Impairment of smell is more commonly related to chronic rhinosinusitis with nasal polyps (CRSwNP) than without, especially when asthma and/or NSAID-exacerbated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Impairment of smell is more commonly related to chronic rhinosinusitis with nasal polyps (CRSwNP) than without, especially when asthma and/or NSAID-exacerbated respiratory disease and type 2 inflammation are also present. Therapeutic options include intranasal and systemic corticosteroids, surgery, and, more recently, biological therapy. We summarize current knowledge on the effect of biologics on olfaction in patients with CRSwNP.
METHODS
We performed a systematic search of the PubMed and Cochrane databases from January 2001 to June 2022. The inclusion criteria were as follows: adult patients with CRS treated with dupilumab, omalizumab, mepolizumab, benralizumab, or reslizumab; and studies published in English reporting outcomes for sense of smell based on psychophysical and/or subjective tools. We excluded reports that did not assess CRSwNP, loss of smell evaluated with a method other than those accepted in the inclusion criteria, review articles, and expert opinions. No funding was received.
RESULTS
Dupilumab has demonstrated rapid and sustained long-term improvement in smell in clinical trials and in real life. Omalizumab improves smell at 24 weeks. This improvement is maintained in the long-term, although it is not clinically relevant. Mepolizumab and benralizumab improved smell in the long term based on a subjective scale. No studies examining the improvement in smell in patients with CRSwNP treated with reslizumab were found. Indirect comparisons by meta-analysis consistently conclude that dupilumab is the most effective biologic for improving impaired sense of smell.
CONCLUSION
Dupilumab seems to be more efficacious for improving the sense of smell than omalizumab, mepolizumab, and benralizumab.
Topics: Adult; Humans; Antibodies, Monoclonal; Nasal Polyps; Omalizumab; Smell; Rhinosinusitis; Chronic Disease; Sinusitis; Rhinitis; Quality of Life
PubMed: 37669083
DOI: 10.18176/jiaci.0939