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Lung Jun 2024Treatment of allergic bronchopulmonary aspergillosis (ABPA) is challenging. Biological therapies have been reported as adjunctive treatments for ABPA, primarily in case... (Review)
Review
BACKGROUND
Treatment of allergic bronchopulmonary aspergillosis (ABPA) is challenging. Biological therapies have been reported as adjunctive treatments for ABPA, primarily in case series or case reports. This study aimed to analyze the efficacy of biologics for managing ABPA both qualitatively and quantitatively.
METHODS
All articles on APBA published in October 2023 were searched in PubMed, Web of Science, ClinicalTrials.gov, and Embase databases. The effects of interest were the mean changes from baseline for outcomes, including exacerbation rates, oral corticosteroids usage (OCS), and total immunoglobulin E (IgE) levels. Reported outcomes were quantitatively synthesized by usual or individual patient data (IPD) meta-analyses. PROSPERO registration number: CRD42022373396.
RESULTS
A total of 86 studies were included in the systematic review including 346 patients. Sixteen studies on omalizumab were pooled for the usual meta-analysis. Omalizumab therapy significantly reduced exacerbation rates (- 2.29 [95%CI - 3.32, - 1.26]), OCS dosage (- 10.91 mg [95%CI - 18.98, - 2.85]), and total IgE levels (- 273.07 IU/mL [95%CI - 379.30, - 166.84]), meanwhile improving FEV1% predicted (10.09% [95%CI 6.62, 13.55]). Thirty-one studies on dupilumab, mepolizumab, or benralizumab were pooled to perform an IPD meta-analysis, retrospectively. Both dupilumab and mepolizumab significantly reduced exacerbation rates, OCS, and total IgE levels. Benralizumab showed a similar trend, but it was not statistically significant. Tezepelumab showed weak evidence of its effects on ABPA. All five biologics led to milder clinical symptoms (e.g., cough, wheezing) with serious adverse effects that happened once in omalizumab treatment.
CONCLUSION
These results indicate the clinical benefit of omalizumab, dupilumab, and mepolizumab in patients with ABPA. Further randomized, controlled studies with a larger sample size and longer follow-up are needed to confirm these findings.
PubMed: 38898129
DOI: 10.1007/s00408-024-00717-y -
Clinical Pharmacokinetics May 2024Although little information is available on the pharmacokinetics (PK) of monoclonal antibodies (mAbs) during pregnancy, multiple mAbs are being used during pregnancy for...
BACKGROUND AND OBJECTIVE
Although little information is available on the pharmacokinetics (PK) of monoclonal antibodies (mAbs) during pregnancy, multiple mAbs are being used during pregnancy for various indications. The aim of this systematic literature review was to characterize the PK of mAbs throughout pregnancy.
METHODS
A systematic literature search was carried out in PubMed and Embase on 21 April 2023. Articles were included when information on PK or exposure parameters of mAbs in pregnant women was available.
RESULTS
A total of 42 relevant articles were included, of which eight discussed adalimumab, three certolizumab pegol, five eculizumab, one golimumab, 12 infliximab (IFX), two natalizumab, one canakinumab, one omalizumab, five tocilizumab, eight ustekinumab, and five vedolizumab. One of the 42 studies reported information on clearance (CL) and volume of distribution (VD) of IFX; all other studies only reported on serum concentrations in the pre-pregnancy state, different trimesters, and the postpartum period. For all of the assessed mAbs except IFX, serum concentrations were similar to concentrations in the pre-pregnancy state or modestly decreased. In contrast, IFX trough concentrations generally increased in the second and third trimesters in comparison to the non-pregnant state.
CONCLUSION
Available information suggests that the anatomical and physiological changes throughout pregnancy may have meaningful effects on the PK of mAbs. For most mAbs (not IFX), modestly higher dosing (per mg) maybe needed during pregnancy to sustain a similar serum exposure compared to pre-pregnancy.
Topics: Humans; Pregnancy; Female; Antibodies, Monoclonal; Pregnancy Complications
PubMed: 38583128
DOI: 10.1007/s40262-024-01370-7 -
Deutsches Arzteblatt International Oct 2019Monoclonal antibodies (mAb) and fusion proteins (FP) are increasingly being used in children and adolescents. In this review, we analyze the evidence for their safety...
BACKGROUND
Monoclonal antibodies (mAb) and fusion proteins (FP) are increasingly being used in children and adolescents. In this review, we analyze the evidence for their safety and efficacy in the treatment of the most common chronic inflammatory diseases.
METHODS
We systematically searched PubMed, AWMF.org, and other databases for high-quality trials (i.e., randomized controlled trials with clinical primary endpoints) and guidelines published at any time up to 10 December 2018 that dealt with mAb and FP that are approved for pediatric use. The search term was "monoclonal anti- body/fusion protein [e. g. adalimumab] AND children."
RESULTS
The 620 hits included 25 high-quality trials (20 of them manufacturer- sponsored) on 9 mAb/FP (omalizumab, adalimumab, etanercept, ustekinumab, infliximab, golimumab, anakinra, canakinumab, tocilizumab, and abatacept), as well as 6 guidelines (3 each of levels S3 and S2k) on the treatment of bronchial asthma, psoriasis, juvenile idopathic arthritis, and chronic inflammatory bowel diseases. For none of these conditions are mAb and FP the drugs of first choice. Adverse drug effects are rare but sometimes severe (infection, immune dysregulation, tumors).
CONCLUSION
The retrieved trials have deficiencies that make it difficult to reliably evaluate the efficacy, safety, and utility of mAb/FP for children and adolescents with chronic inflammatory diseases. mAb/FP nonetheless represent a treatment option to be considered in case conventional immune-modulating drugs are ineffective. Researcher-initiated, high-quality trials and manufacturer-independent, systematic long-term evaluations of adverse effects (e.g., tumors) are sorely needed.
Topics: Adolescent; Antibodies, Monoclonal; Biological Products; Child; Humans; Proteins; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31711560
DOI: 10.3238/arztebl.2019.0703 -
Clinical and Experimental Allergy :... Oct 2019We investigated whether prolonged treatment with omalizumab influences development or progression of solid epithelial cancer in patients with atopic asthma or chronic... (Meta-Analysis)
Meta-Analysis
Influence of prolonged treatment with omalizumab on the development of solid epithelial cancer in patients with atopic asthma and chronic idiopathic urticaria: A systematic review and meta-analysis.
OBJECTIVE
We investigated whether prolonged treatment with omalizumab influences development or progression of solid epithelial cancer in patients with atopic asthma or chronic idiopathic urticaria.
DESIGN
Systematic review and meta-analysis of intervention and observational studies. Randomized controlled trials were assessed for risk of bias using the Cochrane Risk of Bias tool, comparative observational studies were assessed using the Newcastle-Ottawa Scale, and non-comparative observational studies were assessed using the Joanna Briggs Institute Checklist for Prevalence Studies.
DATA SOURCES
We searched MEDLINE, EMBASE, Cochrane Library and grey literature for eligible studies to November 2017. All searches were updated in January 2019.
ELIGIBILITY CRITERIA FOR INCLUDED STUDIES
Randomized, quasi-randomized, controlled clinical trials and observational studies were included if they involved patients ≥ 12 years with moderate-to-severe persistent asthma or chronic idiopathic urticaria treated with omalizumab for ≥ 40 weeks. Eligible comparators included standard of care, placebo, cromoglycate or no treatment.
RESULTS
One hundred and sixty seven unique studies were eligible for inclusion; however, only twelve (7.2%, n = 11 758) reported any outcome of interest, none of which involved patients with urticaria. 195 cancer events were reported. We found no statistically significant increase in the odds of study-emergent solid epithelial cancer in patients randomized to long-term treatment with omalizumab compared to standard of care (Peto OR: 0.65, 95% CI: 0.11, 3.74, I = 41%). Less than one per cent of participants of non-comparative observational studies (n = 2350) were diagnosed with a solid epithelial tumour (meta-proportion: 0.86% [95% CI: 0.24, 1.86%, I = 56%]). In the only comparative observational study reporting on cancer, the proportion of study-emergent solid epithelial tumour events was nearly identical in both study groups (omalizumab: 2.3%, standard of care: 2.2%).
CONCLUSIONS
There is insufficient evidence to determine whether long-term treatment with omalizumab influences development or progression of solid epithelial cancer in these patient populations. PROSPERO registration # CRD 42018082211.
Topics: Asthma; Chronic Urticaria; Female; Humans; Male; Neoplasms, Glandular and Epithelial; Neoplasms, Second Primary; Omalizumab; Randomized Controlled Trials as Topic; Time Factors
PubMed: 31295369
DOI: 10.1111/cea.13457 -
International Forum of Allergy &... Feb 2020Chronic rhinosinusitis (CRS) refractory to medical and surgical treatment is challenging. It impacts patients' quality of life significantly. The pathophysiology of CRS...
BACKGROUND
Chronic rhinosinusitis (CRS) refractory to medical and surgical treatment is challenging. It impacts patients' quality of life significantly. The pathophysiology of CRS has some similarities to allergic asthma and allergic rhinitis (AR) and includes eosinophilia, T-helper cell 2 cytokines, and local immunoglobilin E formation. Monoclonal antibody therapy has been used successfully in asthma and AR and more recently in CRS. Our was aim to systematically review the literature and identify the role of monoclonal antibodies (MAbs) in the treatment of CRS with polyps (CRSwNP) and without polyps (CRSsNP), especially with regard to comparability with current medical treatment, efficacy, and risk of complications. In addition, the role of surgery and biologics was evaluated.
METHODS
We identified at total of 5341 relevant studies after a comprehensive database search. Six studies met the inclusion criteria, all 6 randomized, controlled trials.
RESULTS
Treatment with omalizumab and mepolizumab demonstrated improvements in endoscopic nasal polyp score (EPS) and symptoms score in patients with CRSwNP when compared with placebo. Reslizumab reduced nasal polyp size in patients with raised intranasal interleukin-5 levels. Dupilumab treatment resulted in a 70% reduction in EPS compared with 20% in the placebo group (p < 0.001). These MAbs target different inflammatory markers involved in the pathophysiology of CRSwNP. None of the studies reported on CRSsNP or combined surgery with biologics. No severe adverse events were reported.
CONCLUSION
Evidence demonstrates that use of MAbs leads to clinical improvement in CRSwNP. However, further research is required to determine their long-term effects, comparability to other medical treatments, and potential side effects.
Topics: Antibodies, Monoclonal; Biological Products; Chronic Disease; Humans; Rhinitis; Sinusitis
PubMed: 31869863
DOI: 10.1002/alr.22473 -
Pediatric Allergy and Immunology :... May 2024Tree nut allergy is a lifelong and potentially life-threatening condition. The standard of care is strictly avoiding the culprit nut and treating accidental reactions... (Review)
Review
Tree nut allergy is a lifelong and potentially life-threatening condition. The standard of care is strictly avoiding the culprit nut and treating accidental reactions symptomatically. To evaluate potential therapeutic options for desensitizing patients with IgE-mediated tree nut allergy, we systematically searched three bibliographic databases for studies published until January 2024. We looked for active treatments of IgE-mediated allergy to tree nuts (walnut, hazelnut, pistachio, cashew, almond, pecan, macadamia nut, and brazil nut). We focused on allergen-specific immunotherapy (AIT) using oral (OIT), sublingual (SLIT), epicutaneous (EPIT), or subcutaneous (SCIT) delivery, or other disease-modifying treatments. We found 19 studies that met our criteria: 3 studies investigated sublingual immunotherapy, 5 studied oral immunotherapy to a single tree nut, and 6 used multi-food oral immunotherapy with or without omalizumab. The remaining studies investigated the effectiveness of monoclonal antibodies or IgE-immunoadsorption in multi-food allergic patients, including patients with tree nut allergy. The heterogeneity of the studies prevented pooling and meta-analysis. Oral immunotherapy, single or multi-nut, with or without omalizumab, was the most studied approach and appears effective in conferring protection from accidental exposures. Omalizumab monotherapy is the only approved alternative management for reducing allergic reactions that may occur with accidental exposure.
Topics: Humans; Nut Hypersensitivity; Immunoglobulin E; Desensitization, Immunologic; Allergens; Nuts; Child; Omalizumab
PubMed: 38727626
DOI: 10.1111/pai.14132 -
Allergy Jan 2021Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of...
Biologicals have transformed the management of severe disease phenotypes in asthma, atopic dermatitis, and chronic spontaneous urticaria. As a result, the number of approved biologicals for the treatment of atopic diseases is continuously increasing. Although atopic diseases are among the most common diseases in the reproductive age, investigations, and information on half-life, pharmacokinetics defining the neonatal Fc receptors (FcRn) and most important safety of biologicals in pregnancy are lacking. Given the complex sequence of immunological events that regulate conception, fetal development, and the intrauterine and postnatal maturation of the immune system, this information is of utmost importance. We conducted a systematic review on biologicals in pregnancy for indications of atopic diseases. Evidence in this field is scarce and mainly reserved to reports on the usage of omalizumab. This lack of evidence demands the establishment of a multidisciplinary approach for the management of pregnant women who receive biologicals and multicenter registries for long-term follow-up, drug trial designs suitable for women in the reproductive age, and better experimental models that represent the human situation. Due to the very long half-life of biologicals, preconception counseling and healthcare provider education are crucial to offer the best care for mother and fetus. This position paper integrates available data on safety of biologicals during pregnancy in atopic diseases via a systematic review with a detailed review on immunological considerations how inhibition of different pathways may impact pregnancy.
Topics: Asthma; Biological Factors; Biological Products; Dermatitis, Atopic; Female; Humans; Infant, Newborn; Multicenter Studies as Topic; Omalizumab; Pregnancy
PubMed: 32189356
DOI: 10.1111/all.14282 -
Clinical and Experimental Allergy :... Nov 2020Monoclonal antibody therapies have a growing role in treating refractory airway disease.
BACKGROUND
Monoclonal antibody therapies have a growing role in treating refractory airway disease.
OBJECTIVE
The review aimed to summarize the response of respiratory mucosa to monoclonal antibody treatments in inflammatory airway conditions.
DESIGN
We conducted a systematic review including risk of bias assessment.
DATA SOURCES
MEDLINE, EMBASE and PubMed from 1 January 2000 to 16 November 2019 were searched.
ELIGIBILITY CRITERIA
Eligible studies assessed the immunological and histological response of airway mucosa to monoclonal antibody therapy compared with baseline or a comparison group in patients with respiratory diseases (asthma, chronic rhinosinusitis and allergic rhinitis). Any prospective interventional studies, including randomized controlled trials (RCTs) and single-arm trials, were eligible.
RESULTS
There were 4195 articles screened, and full-text analysis produced n = 11 studies with extractable data. Nine were RCTs, and two were single-arm trials. These studies focused on asthma (n = 9 articles), chronic rhinosinusitis (n = 1) and allergic rhinitis (n = 1). Five monoclonal antibody drugs were assessed (omalizumab, mepolizumab, dupilumab, benralizumab and tralokinumab). Risk of bias was low (n = 6) or unclear (n = 3) in the RCTs and moderate in the single-arm trials. Omalizumab reduced the mucosal concentration of its target, IgE. Dupilumab reduced the concentration of one of its targets, IL-13, but not IL-4. Omalizumab, mepolizumab and benralizumab reduced tissue eosinophil cell density. Dupilumab decreased mucosal eosinophil granule proteins. Tralokinumab did not affect airway mucosa.
CONCLUSIONS
Knowledge of the expected biological response of monoclonal antibody therapy on biomarkers in disease tissue provides an important supplement to data about clinical outcomes. An understanding of the biological effect is essential to identify likely responders, reasons for treatment failure and necessary adjustments to monoclonal antibody treatment. Further investigation into the effect of monoclonal antibody therapy on disease mucosa and more precise endotyping are required to move closer to achieving personalized medicine.
Topics: Adult; Antibodies, Monoclonal; Biomarkers; Female; Humans; Immunity, Mucosal; Male; Middle Aged; Respiratory Mucosa; Respiratory System Agents; Respiratory Tract Diseases; Treatment Outcome; Young Adult
PubMed: 32808380
DOI: 10.1111/cea.13721 -
The Journal of Allergy and Clinical... Jan 2022Recently, pharmacological treatment options for H1-antihistamine-refractory chronic spontaneous urticaria have increased dramatically; however, their effects on... (Meta-Analysis)
Meta-Analysis
Impact of Pharmacological Treatments for Chronic Spontaneous Urticaria with an Inadequate Response to H1-Antihistamines on Health-Related Quality of Life: A Systematic Review and Network Meta-Analysis.
BACKGROUND
Recently, pharmacological treatment options for H1-antihistamine-refractory chronic spontaneous urticaria have increased dramatically; however, their effects on patient-reported outcomes, including health-related quality of life (HRQOL), remain unclear.
OBJECTIVE
To compare the impact of these treatments on HRQOL among H1-antihistamine-refractory patients with chronic spontaneous urticaria.
METHODS
We completed a comprehensive search of the available literature in the electronic databases, gray literature, and preprint reports up to April 19, 2021, with no language restrictions. The primary outcome for evaluation was a change in HRQOL from the baseline, and secondary outcomes included patient unacceptability and other patient-reported outcomes. We used a random-effects network meta-analysis and estimated differences in standardized mean differences (SMDs) and odds ratios with 95% CIs. Evidence-based synthesis was based on magnitudes of effect size, evidence certainty, ranking of treatment effects, and clinically meaningful improvement.
RESULTS
Twelve randomized controlled trials encompassing 1866 adolescent and adult patients were included. Our evidence synthesis analyses revealed that hydroxychloroquine (SMD, -1.00 [-1.61 to -0.39]), 72 mg ligelizumab (SMD, -0.66 [-0.96 to -0.35]), 240 mg ligelizumab (SMD, -0.67 [-0.98 to -0.37]), and 300 mg omalizumab (SMD, -0.53 [-0.67 to -0.39]) significantly improved HRQOL with a moderate beneficial effect. However, the use of hydroxychloroquine seems to be limited by a higher risk of patient unacceptability of treatment. Other secondary outcomes remain inconclusive based on the available evidence.
CONCLUSIONS
Both ligelizumab (72 or 240 mg) and 300 mg omalizumab appeared to be effective treatments for H1-antihistamine-refractory chronic spontaneous urticaria, because they were closely associated with improved HRQOL.
Topics: Adolescent; Adult; Chronic Disease; Chronic Urticaria; Histamine H1 Antagonists; Humans; Network Meta-Analysis; Omalizumab; Quality of Life; Randomized Controlled Trials as Topic; Urticaria
PubMed: 34695599
DOI: 10.1016/j.jaip.2021.10.022 -
Allergy Aug 2021This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared with the standard of care. PubMed,...
This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared with the standard of care. PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CRSwNP-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. RCTs evaluated (dupilumab-2, omalizumab-4, mepolizumab-2, and reslizumab-1) included 1236 adults, with follow-up of 20-64 weeks. Dupilumab reduces the need for surgery (NFS) or oral corticosteroid (OCS) use (RR 0.28; 95% CI 0.20-0.39, moderate certainty) and improves with high certainty smell evaluated with UPSIT score (mean difference (MD) +10.54; 95% CI +9.24 to +11.84) and quality of life (QoL) evaluated with SNOT-22 (MD -19.14; 95% CI -22.80 to -15.47), with fewer treatment-related adverse events (TAEs) (RR 0.95; 95% CI 0.89-1.02, moderate certainty). Omalizumab reduces NFS (RR 0.85; 95% CI 0.78-0.92, high certainty), decreases OCS use (RR 0.38; 95% CI 0.10-1.38, moderate certainty), and improves high certainty smell (MD +3.84; 95% CI +3.64 to +4.04) and QoL (MD -15.65; 95% CI -16.16 to -15.13), with increased TAE (RR 1.73; 95% CI 0.60-5.03, moderate certainty). There is low certainty for mepolizumab reducing NFS (RR 0.78; 95% CI 0.64-0.94) and improving QoL (MD -13.3; 95% CI -23.93 to -2.67) and smell (MD +0.7; 95% CI -0.48 to +1.88), with increased TAEs (RR 1.64; 95% CI 0.41-6.50). The evidence for reslizumab is very uncertain.
Topics: Adult; Biological Products; Humans; Nasal Polyps; Omalizumab; Quality of Life; Sinusitis
PubMed: 33683704
DOI: 10.1111/all.14809