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Journal of Asthma and Allergy 2023Airway hyperresponsiveness (AHR) is a key feature of asthma. Biologic therapies used to treat asthma target specific components of the inflammatory pathway, and their... (Review)
Review
BACKGROUND
Airway hyperresponsiveness (AHR) is a key feature of asthma. Biologic therapies used to treat asthma target specific components of the inflammatory pathway, and their effects on AHR can provide valuable information about the underlying disease pathophysiology. This review summarizes the available evidence regarding the effects of biologics on allergen-specific and non-allergen-specific airway responses in patients with asthma.
METHODS
We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, including risk-of-bias assessment. PubMed and Ovid were searched for studies published between January 1997 and December 2021. Eligible studies were randomized, placebo-controlled trials that assessed the effects of biologics on AHR, early allergic response (EAR) and/or late allergic response (LAR) in patients with asthma.
RESULTS
Thirty studies were identified for inclusion. Bronchoprovocation testing was allergen-specific in 18 studies and non-allergen-specific in 12 studies. Omalizumab reduced AHR to methacholine, acetylcholine or adenosine monophosphate (3/9 studies), and reduced EAR (4/5 studies) and LAR (2/3 studies). Mepolizumab had no effect on AHR (3/3 studies), EAR or LAR (1/1 study). Tezepelumab reduced AHR to methacholine or mannitol (3/3 studies), and reduced EAR and LAR (1/1 study). Pitrakinra reduced LAR, with no effect on AHR (1/1 study). Etanercept reduced AHR to methacholine (1/2 studies). No effects were observed for lebrikizumab, tocilizumab, efalizumab, IMA-638 and anti-OX40 ligand on AHR, EAR or LAR; benralizumab on LAR; tralokinumab on AHR; and Ro-24-7472 on AHR or LAR (all 1/1 study each). No dupilumab or reslizumab studies were identified.
CONCLUSION
Omalizumab and tezepelumab reduced EAR and LAR to allergens. Tezepelumab consistently reduced AHR to methacholine or mannitol. These findings provide insights into AHR mechanisms and the precise effects of asthma biologics. Furthermore, findings suggest that tezepelumab broadly targets allergen-specific and non-allergic forms of AHR, and the underlying cells and mediators involved in asthma.
PubMed: 37496824
DOI: 10.2147/JAA.S410592 -
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 -
Skin Research and Technology : Official... May 2024Omalizumab is the only licensed drug that serves as a third-line treatment for chronic idiopathic urticaria (CIU). The optimum doses of omalizumab remain controversial.... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
Omalizumab is the only licensed drug that serves as a third-line treatment for chronic idiopathic urticaria (CIU). The optimum doses of omalizumab remain controversial. Therefore, this study aims to estimate the efficacy and safety of different doses of omalizumab in the treatment of CIU patients.
MATERIALS AND METHODS
Four databases were searched from the database's creation to April 8, 2023. Several keywords such as omalizumab and urticarias were used to retrieve related studies. The meta-analytical outcomes were analyzed in R 4.2.1 software and Stata 15.1 software. Cochrane risk-of-bias tool Ver. 2 was used to evaluate the risk of bias in randomized controlled trials (RCTs).
RESULTS
In total, 2331 patients were included. Five indexes were employed to assess, including weekly Itch Severity Score (ISS7), weekly Hive Severity Score (HSS7), weekly Urticaria Activity Score (UAS7), Dermatology Life Quality Index (DLQI), and adverse events (AE). A 300 mg dose of omalizumab was the optimum dose to treat CIU, followed by the 150 mg dose. Furthermore, 600 mg of omalizumab only showed a significant difference from the placebo in HSS7. No significant statistical difference was observed in AE. Meta-regression analysis revealed that time, as a covariate, was statistically significant in the comparison of omalizumab 150 mg with placebo.
CONCLUSION
300 mg of omalizumab was the optimum dosage to treat CIU patients, with a 150 mg dose also exhibiting good efficacy. Further studies are required to explore the efficacy and safety of different doses of omalizumab in the treatment of CIU patients.
Topics: Omalizumab; Humans; Chronic Urticaria; Anti-Allergic Agents; Treatment Outcome; Network Meta-Analysis; Randomized Controlled Trials as Topic; Quality of Life; Dose-Response Relationship, Drug
PubMed: 38776128
DOI: 10.1111/srt.13749 -
Frontiers in Immunology 2024Due to comorbidities and associated safety risks, the management of severe atopic dermatitis (AD) in pediatric and adolescent patients poses significant challenges.
IMPORTANCE
Due to comorbidities and associated safety risks, the management of severe atopic dermatitis (AD) in pediatric and adolescent patients poses significant challenges.
OBJECTIVE
To examine the efficacy and safety of systemic therapies for the treatment of moderate-to-severe atopic dermatitis in children and adolescents.
EVIDENCE REVIEW
On Feb 29, 2024, a systematic literature search was conducted in Embase, PubMed, and the Cochrane Central Register of Controlled Trials (Central). No date restrictions were applied. Randomized clinical trials, cohort studies, large case series, and meta-analyses were assessed to evaluate the efficacy (or effectiveness) and/or safety of systemic treatments for moderate-to-severe atopic dermatitis in children and adolescents.
FINDINGS
A preliminary search yielded 1457 results, from which 19 unique articles with a total of 3741 patients were included in the analysis. Overall, the available data for each systemic medication are limited, and the overall quality of the included studies on conventional systemic treatments is relatively low. When Dupilumab was used as a standalone treatment, 30%-40% of infants and toddlers aged 6 months to 2 years achieved EASI-75, while 50% of patients aged 2 to 6 years achieved EASI-75. In children aged 6 to 12 years, 33.0%-59.0% of atopic dermatitis patients achieved EASI-75, and when combined with topical corticosteroids (TCS), 69.7%-74.6% achieved EASI-75. Long-term data showed EASI-75 rates ranging from 75.0% to 94.0% for this age group. For adolescents aged 12 to 18 years, 40%-71% of patients achieved EASI-75 within 12 to 16 weeks, and by week 52, 80.8% of patients achieved EASI-75.Abrocitinib treatment resulted in 68.5%-72.0% of patients achieving EASI-75. Omalizumab treatment at week 24 showed a percentage change in SCORAD scores of -12.4%. In the Methotrexate treatment group, there was a SCORAD change of -26.25% at week 12, while the Cyclosporine A group had a SCORAD change of -25.01%. Patients treated with IVIG (Intravenous Immunoglobulin) showed a -34.4% change in SCORAD percentage scores at week 4, which further decreased by 47.12% at week 24. Patients receiving 4mg of Baricitinib and TCS had a 52.5% rate of EASI-75 at 16 weeks, and patients receiving different doses of upadacitinib had a 63-75% rate of EASI-75 at 16 weeks. The rate of EASI-75 at 16 weeks was around 28% in patients who received various doses of Tralokinumab.The most common adverse events observed were nasopharyngitis, respiratory events and dermatitis atopic.
CONCLUSIONS AND RELEVANCE
Awareness of adverse events and concomitant medications is crucial, and appropriate dosing and frequent laboratory and clinical monitoring are also essential. More real-world evidence and prospective cohort studies analyzing the effectiveness and safety of systemic therapies in children and adolescents are of paramount importance for optimizing personalized, effective, and safe management of the growing population of patients with atopic dermatitis in this age group.
Topics: Humans; Dermatitis, Atopic; Child; Adolescent; Child, Preschool; Treatment Outcome; Severity of Illness Index; Infant; Female; Male; Dermatologic Agents; Antibodies, Monoclonal, Humanized
PubMed: 38812522
DOI: 10.3389/fimmu.2024.1367099 -
The Journal of Allergy and Clinical... Feb 2024Increasing evidence supports the united airway disease concept for the management of upper and lower respiratory tract diseases, particularly in patients with asthma and...
BACKGROUND
Increasing evidence supports the united airway disease concept for the management of upper and lower respiratory tract diseases, particularly in patients with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). However, evidence for a combined approach in asthma and CRSwNP is scarce.
OBJECTIVE
In this systematic review, we focused on the role of biologics in the lung function and quality of life in patients with severe asthma and CRSwNP.
METHODS
We conducted a systematic search of 3 electronic databases using 2 search strategies to identify studies published from January 2010 to March 2022. Quality assessment was performed with the Critical Appraisal Skills Programme.
RESULTS
Of 1030 studies identified, 48 original studies reporting data of benralizumab (12), dupilumab (14), mepolizumab (10), omalizumab (13), and reslizumab (2) were analyzed. Primary diagnosis was mostly asthma or CRSwNP, with only 15 studies, mainly observational, performed in populations with united airway disease. In total, 18 studies reported data on quality of life (mostly 22-item Sino-Nasal Outcome Test score), 8 on lung function (mostly FEV), and 22 on both outcomes. Significant FEV and 22-item Sino-Nasal Outcome Test score improvements were consistently observed after 24-week treatment, and thereafter, mostly in real-world studies that included variable proportions of patients with asthma/CRSwNP.
CONCLUSIONS
The use of biologics in patients with severe asthma and CRSwNP was overall associated with significant improvements in lung function and quality of life. However, we observed a high heterogeneity of populations and outcome measurements across studies. Notwithstanding the need of larger studies, our results reinforce the joint management of asthma and CRSwNP as united airway disease in clinical practice.
PubMed: 37915724
DOI: 10.1016/j.jacig.2023.100174 -
Therapeutic Advances in Respiratory... 2024With the rise of targeted treatments for asthma, treatment with omalizumab is a new option. (Meta-Analysis)
Meta-Analysis
BACKGROUND
With the rise of targeted treatments for asthma, treatment with omalizumab is a new option.
OBJECTIVES
To assess the improvement of pulmonary function with additional omalizumab treatment in patients (⩾6 years old) with moderate-to-severe allergic asthma.
DATA SOURCES AND METHODS
Observational studies of randomized controlled trials of add-on omalizumab for the treatment of patients with moderate-to-severe allergic asthma, published from the establishment till August 2022, were retrieved from WAN FANG DATA, PubMed, CNKI, Embase, Cochrane, and Web of Science databases. Data extraction and quality evaluation were performed on the literature that met the inclusion criteria, using RevMan 5.3 to analyze the data.
RESULTS
A total of 11 randomized controlled clinical trials were included, involving a total of 3578 patients with asthma, 1856 patients in the omalizumab group, and 1722 patients in the control group. The improvement in Forced expiratory volume in 1 s as a percentage of predicted normal and Forced expiratory volume in 1 s was more pronounced in the omalizumab-treated group [MD = 3.91, 95% confidence interval (CI): 1.89-5.94, = 0.0002; MD = 0.09, 95% CI: 0.05-0.13, < 0.0001], while the improvement in Morning Peak expiratory flow rate was not statistically different between the two groups (MD = 3.64, 95% CI: -22.17-29.45, = 0.78).
CONCLUSION
Additional omalizumab treatment showed some improvement in lung function in patients with moderate-to-severe asthma.
TRIAL REGISTRATION
PROSPERO ID:CRD42022378498.
Topics: Humans; Anti-Asthmatic Agents; Asthma; Forced Expiratory Volume; Lung; Omalizumab; Treatment Outcome
PubMed: 38235607
DOI: 10.1177/17534666231221771 -
The World Allergy Organization Journal Apr 2024The stability, efficacy, and safety of omalizumab at different doses and regimens for chronic spontaneous urticaria (CSU) are yet to be studied.
BACKGROUND
The stability, efficacy, and safety of omalizumab at different doses and regimens for chronic spontaneous urticaria (CSU) are yet to be studied.
OBJECTIVE
A systematic review (SR) with meta-analysis (MA) and trial sequential analysis (TSA) was performed to assess the efficacy and safety of omalizumab in CSU.
METHODS
Randomised controlled trials (RCTs) of administering omalizumab versus placebo for CSU were searched. Random-effects MAs were performed using planned subgroup analyses. TSA was performed to control for the risk of random errors and assess the stability of our MA results. Publication bias was visually assessed using a contour-enhanced funnel plot and the trim-and-fill method. The quality of RCTs was assessed using the Cochrane Risk of Bias Tool 2.
RESULTS
Twelve studies met the inclusion criteria. Omalizumab had remarkable effects on the patient percentage of the weekly urticaria activity score is zero (UAS = 0) [RR 4.64, 95% CI (3.38, 6.37)], percentage of no angioedema-burdened days [MD 3.15, 95% CI (0.10, 6.19], patient percentage of UAS ≤6 [RR 3.05, 95% CI (2.46, 3.78)], and patient percentage of the weekly itch severity score minimally important difference (ISS7 MID) [RR 1.50, 95% CI (1.36, 1.66)]. Omalizumab was well tolerated across studies [RR 0.98, 95% CI (0.90, 1.08)]. TSA confirmed the above results, except for "the percentage of no angioedema-burdened day".
CONCLUSION
Among the different doses and courses assessed, omalizumab (300 mg, 12 weeks) can be recommended as an effective treatment for patients with CSU. However, whether omalizumab improves angioedema requires further investigation. The clinical management of angioedema accompanying CSU requires further attention.
PubMed: 38623321
DOI: 10.1016/j.waojou.2024.100898 -
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