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Clinical Otolaryngology : Official... Jul 2024Leukotrienes play a significant role in the pathogenesis of adenoid hypertrophy (A.H.). Therefore, we aimed to analyse the role of montelukast, a leukotriene receptor... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Leukotrienes play a significant role in the pathogenesis of adenoid hypertrophy (A.H.). Therefore, we aimed to analyse the role of montelukast, a leukotriene receptor antagonist, alone or in combination with mometasone, a potent local intranasal steroid, for the treatment of A.H.
METHODS
Participants were children with A.H. were treated with montelukast alone or montelukast and mometasone furoate. The main outcome measures were effect of montelukast on clinical symptoms of A.H. A literature review was conducted using online search engines, Cochrane Library, PubMed, Web of Science and Scopus, for randomized clinical trials assessing children with A.H. treated with montelukast alone or montelukast and mometasone furoate. Seven randomized clinical trials (RCTs) were included with 742 children.
RESULTS
Our study reveals that montelukast alone or in combination with intranasal mometasone furoate significantly improves clinical symptoms of adenoid hypertrophy such as snoring, sleeping disturbance, mouth breathing and A/N ratio. Montelukast was superior to placebo in decreasing snoring (SMD = -1.00, 95% CI [-1.52, -0.49]), sleep discomfort (SMD = -1.26, 95% CI [-1.60, -0.93]), A/N ratio (MD = -0.11, 95% CI [-0.14, -0.09]) and mouth breathing (SMD = -1.36, 95% CI [-1.70, -1.02]). No difference was detected between montelukast and mometasone versus mometasone alone in snoring (SMD = -0.21, 95%CI [-0.69, 0.27]); however, the combination group was superior to the mometasone alone in mouth breathing (SMD = -0.46, 95% CI [-0.73, -0.19]).
CONCLUSIONS
The limitation of studies included a small sample size, with an overall low to medium quality. Thus, further larger, higher-quality RCTs are recommended to provide more substantial evidence.
Topics: Humans; Adenoids; Cyclopropanes; Quinolines; Acetates; Sulfides; Hypertrophy; Child; Mometasone Furoate; Leukotriene Antagonists; Administration, Intranasal; Drug Therapy, Combination; Treatment Outcome
PubMed: 38700144
DOI: 10.1111/coa.14169 -
Sleep Medicine Apr 2024Pediatric obstructive sleep apnea (OSA) is a common disease that can have significant negative impacts on a child's health and development. A comprehensive evaluation of... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Pediatric obstructive sleep apnea (OSA) is a common disease that can have significant negative impacts on a child's health and development. A comprehensive evaluation of different pharmacologic interventions for the treatment of OSA in children is still lacking.
OBJECTIVE
This study aims to conduct a comprehensive systematic review and network meta-analysis of pharmacological interventions for the management of obstructive sleep apnea in pediatric population.
DATA SOURCES
PubMed, Web of Science, Embase, The Cochrane Library, and CNKI were searched from 1950 to November 2022 for pediatric OSA.
STUDY SELECTION
Multiple reviewers included Randomized controlled trials (RCTs) concerning drugs on OSA in children.
DATA EXTRACTION AND SYNTHESIS
Multiple observers followed the guidance of the PRISMA NMA statement for data extraction and evaluation. Bayesian network meta-analyses(fixed-effect model) were performed to compare the weighted mean difference (WMD), logarithmic odds ratios (log OR), and the surface under the cumulative ranking curves (SUCRA) of the included pharmacological interventions. Our protocol was registered in PROSPERO website (CRD42022377839).
MAIN OUTCOME(S) AND MEASURE(S)
The primary outcomes were improvements in the apnea/hypopnea index (AHI), while secondary outcomes included adverse events and the lowest arterial oxygen saturation (SaO2).
RESULTS
17 RCTs with a total of 1367 children with OSA aged 2-14 years that met the inclusion criteria were eventually included in our systematic review and network meta-analysis. Ten drugs were finally included in the study. The results revealed that Mometasone + Montelukast (WMD-4.74[95%CrIs -7.50 to -2.11], Budesonide (-3.45[-6.86 to -0.15], and Montelukast(-3.41[-5.45 to -1.39] exhibited significantly superior therapeutic effects compared to the placebo concerning apnea hypopnea index (AHI) value with 95%CrIs excluding no effect. Moreover, Mometasone + Montelukast achieved exceptionally high SUCRA values for both AHI (85.0 %) and SaO2 (91.0 %).
CONCLUSIONS AND RELEVANCE
The combination of mometasone furoate nasal spray and oral montelukast sodium exhibits the highest probability of being the most effective intervention. Further research is needed to investigate the long-term efficacy and safety profiles of these interventions in pediatric patients with OSA.
Topics: Child; Humans; Network Meta-Analysis; Acetates; Sleep Apnea, Obstructive; Mometasone Furoate; Cyclopropanes; Quinolines; Sulfides
PubMed: 38460418
DOI: 10.1016/j.sleep.2024.01.030 -
PloS One 2023The life quality of about two-thirds of patients with COVID-19 is affected by related olfactory dysfunctions. The negative impact of olfactory dysfunction ranged from...
Effect of any form of steroids in comparison with that of other medications on the duration of olfactory dysfunction in patients with COVID-19: A systematic review of randomized trials and quasi-experimental studies.
BACKGROUND
The life quality of about two-thirds of patients with COVID-19 is affected by related olfactory dysfunctions. The negative impact of olfactory dysfunction ranged from the decreased pleasure of eating to impaired quality of life. This research aimed to provide a comprehensive understanding of the effects of corticosteroid treatments by comparing that to other currently available treatments and interventions.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist's 27-point checklist was used to conduct this review. PubMed (Public/Publisher MEDLINE), PubMed Central and EMBASE (Excerpta Medica Database) databases were conveniently selected and Boolean search commands were used for a comprehensive literature search. Five core search terms were "effects of treatments", " COVID-19-related olfactory dysfunction", "corticosteroids", "treatments" and "interventions". The reporting qualities of the included studies were appraised using JBI (Joanna Briggs Institute) appraisal tools. The characteristics of the 21 experimental studies with a total sample (of 130,550) were aggregated using frequencies and percentages and presented descriptively. The main interventions and their effects on the duration of the COVID-19-related olfactory dysfunction were narratively analyzed.
RESULTS
Among patients with COVID-19, the normal functions of the olfactory lobe were about 23 days earlier to gain with the treatments of fluticasone and triamcinolone acetonide nasal spray compared with that of mometasone furoate nasal spray and oral corticosteroid. The smell loss duration was reduced by fluticasone and triamcinolone acetonide nasal spray 9 days earlier than the inflawell syrup and 16 days earlier than the lavender syrup. The nasal spray of corticosteroids ended the COVID-19-related smell loss symptoms 2 days earlier than the zinc supplementation, about 47 days earlier than carbamazepine treatment and was more effective than palmitoylethanolamide (PEA) and luteolin and omega-3 supplementations and olfactory training. Treatment with oral corticosteroid plus olfactory training significantly improved Threshold, Discrimination and Identification (TDI) scores compared with olfactory training alone. A full dose of the COVID-19 vaccination was not uncertain to reduce the COVID-19-related smell loss duration.
CONCLUSION
Corticosteroid treatment is effective in reducing the duration of COVID-19-related smell loss and olfactory training, the basic, essential and effective intervention, should be used as a combination therapy.
Topics: Humans; Nasal Sprays; Anosmia; Quality of Life; Triamcinolone Acetonide; COVID-19; Randomized Controlled Trials as Topic; Steroids; Adrenal Cortex Hormones; Fluticasone
PubMed: 37531338
DOI: 10.1371/journal.pone.0288285 -
Frontiers in Pharmacology 2023No evidence shows that one intranasal corticosteroid (INCS) is better than another for treating moderate-to-severe allergic rhinitis (AR). This network meta-analysis... (Review)
Review
Comparative efficacy and acceptability of licensed dose intranasal corticosteroids for moderate-to-severe allergic rhinitis: a systematic review and network meta-analysis.
No evidence shows that one intranasal corticosteroid (INCS) is better than another for treating moderate-to-severe allergic rhinitis (AR). This network meta-analysis assessed the comparative efficacy and acceptability of licensed dose aqueous INCSs. PubMed/MEDLINE, Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials were searched until 31 March 2022. Eligible studies included randomized controlled trials comparing INCSs with placebo or other types of INCSs in patients with moderate-to-severe allergic rhinitis. Two reviewers independently screened and extracted data following the Preferred Reporting Items in Systematic Reviews and Meta-analysis guideline. A random-effects model was used for data pooling. Continuous outcomes were expressed as standardized mean difference (SMD). The primary outcomes were the efficacy in improving total nasal symptom score (TNSS) and treatment acceptability (the study dropout). We included 26 studies, 13 with 5,134 seasonal AR patients and 13 with 4,393 perennial AR patients. Most placebo-controlled studies had a moderate quality of evidence. In seasonal AR, mometasone furoate (MF) was ranked the highest efficacy, followed by fluticasone furoate (FF), ciclesonide (CIC), fluticasone propionate and triamcinolone acetonide (TAA) (SMD -0.47, 95% CI: -0.63 to -0.31; -0.46, 95% CI: -0.59 to -0.33; -0.44, 95% CI: -0.75 to -0.13; -0.42, 95% CI: -0.67 to -0.17 and -0.41, 95% CI: -0.81 to -0.00), In perennial AR, budesonide was ranked the highest efficacy, followed by FF, TAA, CIC, and MF (SMD -0.43, 95% CI: -0.75 to -0.11; -0.36, 95% CI: -0.53 to -0.19; -0.32, 95% CI: -0.54 to -0.10; -0.29, 95% CI: -0.48 to -0.11; and -0.28, 95% CI: -0.55 to -0.01). The acceptability of all included INCSs was not inferior to the placebo. According to our indirect comparison, some INCSs have superior efficacy to others with moderate quality of evidence in most placebo-controlled studies for treating moderate-to-severe AR.
PubMed: 37288109
DOI: 10.3389/fphar.2023.1184552 -
Supportive Care in Cancer : Official... Jun 2023Radiation dermatitis (RD) is a frequently occurring adverse reaction during radiotherapy in cancer patients. While the use of topical corticosteroids (TCs) is common for... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Radiation dermatitis (RD) is a frequently occurring adverse reaction during radiotherapy in cancer patients. While the use of topical corticosteroids (TCs) is common for the treatment of RD, its role in preventing severe reactions remains unclear. This systematic review and meta-analysis aim to evaluate the evidence on the use of TCs as prophylaxis of RD.
METHODS
A systematic search was conducted using OVID MedLine, Embase, and Cochrane databases (between 1946 and 2023) to identify studies examining TC use in the prevention of severe RD. Statistical analysis was completed using RevMan 5.4 to calculate pooled effect sizes and 95% confidence intervals. Forest plots were then developed using a random effects model.
RESULTS
Ten RCTs with a total of 1041 patients met the inclusion criteria. Six studies reported on mometasone furoate (MF) and four studies reported on betamethasone. Both TCs were associated with a significant improvement in the prevention of moist desquamation [OR = 0.34, 95% CI [0.25, 0.47], p < 0.00001], but betamethasone was found to be more effective than MF [OR = 0.29, 95% CI [0.18, 0.46], p < 0.00001 and OR = 0.39, 95% CI [0.25, 0.61], p < 0.0001, respectively]. A similar finding was seen in reducing the development of grade 2 or higher RD according to the Radiation Therapy Oncology Group scale.
CONCLUSIONS
The current evidence supports the use of TCs in preventing severe reactions of RD. Both MF and betamethasone were found to be effective; however, betamethasone, a higher potency TC, is more effective despite MF being more commonly reported in literature.
Topics: Humans; Dermatologic Agents; Betamethasone; Radiodermatitis; Adrenal Cortex Hormones
PubMed: 37280403
DOI: 10.1007/s00520-023-07820-5 -
EClinicalMedicine Apr 2023Acute radiation dermatitis (ARD) commonly develops in cancer patients undergoing radiotherapy and is often characterized by erythema, desquamation, and pain. A... (Review)
Review
Acute radiation dermatitis (ARD) commonly develops in cancer patients undergoing radiotherapy and is often characterized by erythema, desquamation, and pain. A systematic review was conducted to summarize the current evidence on interventions for the prevention and management of ARD. Databases were searched from 1946 to September 2020 to identify all original studies that evaluated an intervention for the prevention or management of ARD, with an updated search conducted in January 2023. A total of 235 original studies were included in this review, including 149 randomized controlled trials (RCTs). Most interventions could not be recommended due to a low quality of evidence, lack of supporting evidence, or conflicting findings across multiple trials. Photobiomodulation therapy, Mepitel® film, mometasone furoate, betamethasone, olive oil, and oral enzyme mixtures showed promising results across multiple RCTs. Recommendations could not be made solely based on the published evidence due to limited high-quality evidence. As such, Delphi consensus recommendations will be reported in a separate publication.
PubMed: 37181415
DOI: 10.1016/j.eclinm.2023.101886 -
European Archives of... Apr 2022GSP301 is a fixed-dose combination of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid). This meta-analysis aims to evaluate the efficacy... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
GSP301 is a fixed-dose combination of olopatadine hydrochloride (antihistamine) and mometasone furoate (corticosteroid). This meta-analysis aims to evaluate the efficacy and safety of GSP301 in the treatment of allergic rhinitis.
METHODS
A systematic review and meta-analysis were conducted. The data were collected from PubMed, Cochrane Central Register of Controlled Trials and Embase databases till June 2021. In patients with AR, short-term (2/6 weeks) and long-term (52 weeks) effects of GSP301 were assessed. Average morning and evening 12-h reflective total nasal symptom score (rTNSS), instantaneous total nasal symptom score (iTNSS), reflective total ocular symptom score (rTOSS), instantaneous total ocular symptom score(iTOSS), Physician-assessed nasal symptom score (PNSS), rhinoconjunctivitis quality of life (RQLQ), rhinitis control assessment test (RCAT) and adverse events (AEs) were measured.
RESULTS
Five randomized controlled trials were included. GSP301 showed greatly improvement in rTNSS (MD = - 0.99; [95% CI - 1.19 to - 0.79]; P < 0.01; I = 0), iTNSS (MD = - 1.05; [95% CI - 1.44 to - 0.67]; P < 0.01; I > 50%), rTOSS (MD = - 0.50; [95% CI - 0.72 to - 0.29]; P < 0.01; I = 0), iTOSS (MD = - 0.64; [95% CI - 1.02 to - 0.26]; P < 0.01; I > 50%), PNSS (MD = - 1.01; [95% CI - 1.32 to - 0.69]; P < 0.01; I = 22.13%), RQLQ (MD = - 0.43; [95% CI - 0.57 to - 0.30]; P < 0.01; I = 0%) and RCAT (MD = 1.94; [95% CI 1.43-2.45]; P < 0.01; I = 0%) in the short term. No statistical difference was observed in the outcome of long-term PNSS, RQLQ and RCAT.
CONCLUSION
GSP301 is a safe and well-tolerated medication. It showed short-term benefits for seasonal and perennial AR, but may not help to improve patients' quality of life and rhinitis control in the long run.
Topics: Administration, Intranasal; Anti-Allergic Agents; Double-Blind Method; Humans; Mometasone Furoate; Nasal Sprays; Olopatadine Hydrochloride; Quality of Life; Rhinitis, Allergic; Rhinitis, Allergic, Seasonal; Treatment Outcome
PubMed: 34591150
DOI: 10.1007/s00405-021-07085-w -
The Cochrane Database of Systematic... Jul 2021Loss of olfactory function is well recognised as a cardinal symptom of COVID-19 infection, and the ongoing pandemic has resulted in a large number of affected...
BACKGROUND
Loss of olfactory function is well recognised as a cardinal symptom of COVID-19 infection, and the ongoing pandemic has resulted in a large number of affected individuals with abnormalities in their sense of smell. For many, the condition is temporary and resolves within two to four weeks. However, in a significant minority the symptoms persist. At present, it is not known whether early intervention with any form of treatment (such as medication or olfactory training) can promote recovery and prevent persisting olfactory disturbance. OBJECTIVES: To assess the effects (benefits and harms) of interventions that have been used, or proposed, to prevent persisting olfactory dysfunction due to COVID-19 infection. A secondary objective is to keep the evidence up-to-date, using a living systematic review approach. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane COVID-19 Study Register; Cochrane ENT Register; CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 16 December 2020.
SELECTION CRITERIA
Randomised controlled trials including participants who had symptoms of olfactory disturbance following COVID-19 infection. Individuals who had symptoms for less than four weeks were included in this review. Studies compared any intervention with no treatment or placebo. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were the presence of normal olfactory function, serious adverse effects and change in sense of smell. Secondary outcomes were the prevalence of parosmia, change in sense of taste, disease-related quality of life and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included one study of 100 participants, which compared an intranasal steroid spray to no intervention. Participants in both groups were also advised to undertake olfactory training for the duration of the trial. Data were identified for only two of the prespecified outcomes for this review, and no data were available for the primary outcome of serious adverse effects. Intranasal corticosteroids compared to no intervention (all using olfactory training) Presence of normal olfactory function after three weeks of treatment was self-assessed by the participants, using a visual analogue scale (range 0 to 10, higher scores = better). A score of 10 represented "completely normal smell sensation". The evidence is very uncertain about the effect of intranasal corticosteroids on self-rated recovery of sense of smell (estimated absolute effect 619 per 1000 compared to 520 per 1000, risk ratio (RR) 1.19, 95% confidence interval (CI) 0.85 to 1.68; 1 study; 100 participants; very low-certainty evidence). Change in sense of smell was not reported, but the self-rated score for sense of smell was reported at the endpoint of the study with the same visual analogue scale (after three weeks of treatment). The median scores at endpoint were 10 (interquartile range (IQR) 9 to 10) for the group receiving intranasal corticosteroids, and 10 (IQR 5 to 10) for the group receiving no intervention (1 study; 100 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
There is very limited evidence regarding the efficacy of different interventions at preventing persistent olfactory dysfunction following COVID-19 infection. However, we have identified a small number of additional ongoing studies in this area. As this is a living systematic review, the evidence will be updated regularly to incorporate new data from these, and other relevant studies, as they become available. For this (first) version of the living review, we identified a single study of intranasal corticosteroids to include in this review, which provided data for only two of our prespecified outcomes. The evidence was of very low certainty, therefore we were unable to determine whether intranasal corticosteroids may have a beneficial or harmful effect.
Topics: Administration, Intranasal; Adrenal Cortex Hormones; Bias; COVID-19; Citrus; Confidence Intervals; Humans; Mometasone Furoate; Olfaction Disorders; Phytotherapy; Recovery of Function; Syzygium; Visual Analog Scale
PubMed: 34291812
DOI: 10.1002/14651858.CD013877.pub2 -
International Forum of Allergy &... Jan 2022Intranasal corticosteroids (INCS) are used in the management of sinonasal conditions. Use of exogenous steroids can be associated with hypothalamic-pituitary-adrenal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intranasal corticosteroids (INCS) are used in the management of sinonasal conditions. Use of exogenous steroids can be associated with hypothalamic-pituitary-adrenal axis dysfunction and adrenal insufficiency (AI). We aimed to estimate the rate of AI after INCS use in a meta-analysis, stratified by steroid type and treatment duration.
METHODS
Ovid Medline, Embase Classic, PubMed, Web of Science, and CINAHL databases were searched following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify studies investigating INCS use and AI. AI was defined as morning serum cortisol <550 nmol/L and <80 nmol/L with and without adrenocorticotropic hormone stimulation. INCS were classified as first (beclomethasone dipropionate, triamcinolone acetonide, beclomethasone, budesonide, dexamethasone) and second (ciclesonide, mometasone furoate, and fluticasone propionate) generation. Duration of treatment was classified as short (<1 month), medium (1-12 months), and long-term (>12 months) time periods.
RESULTS
This search identified 3668 articles. A total of 39 studies (1678 patients) were included in the final analysis. The pooled percentage of AI for routinely utilized first- and second-generation INCS was 0.70% (95% confidence interval [CI], 0.29-1.12%). Stratified by type, AI was observed in 0.78% (95% CI, 0.25-1.30%) of first-generation and 0.58% (95% CI, -0.1% to 1.26%) of second-generation steroids. AI was seen in 0.48% (95% CI, -0.01% to 0.96%) of short-term, 1.13% (95% CI, 0.2-2.1%) of medium-term, and 1.67% (95% CI, 0.37-2.9%) of long-term use of INCS.
CONCLUSION
Overall, the use of INCS carries a low risk for AI. Although modest, this risk may differ depending on the length of duration and type of INCS used. Informing patients of these risks is of importance for the treatment of chronic sinonasal conditions.
Topics: Administration, Intranasal; Adrenal Cortex Hormones; Humans; Hypothalamo-Hypophyseal System; Mometasone Furoate; Pituitary-Adrenal System
PubMed: 34260153
DOI: 10.1002/alr.22863 -
The Cochrane Database of Systematic... Apr 2021Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and... (Meta-Analysis)
Meta-Analysis
Regular treatment with formoterol and an inhaled corticosteroid versus regular treatment with salmeterol and an inhaled corticosteroid for chronic asthma: serious adverse events.
BACKGROUND
Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and bronchodilators can result in good control of symptoms, prevention of further morbidity, and improved quality of life. However, an increase in serious adverse events with the use of both regular formoterol and regular salmeterol (long-acting beta₂-agonists) compared with placebo for chronic asthma has been demonstrated in previous Cochrane Reviews. This increase was statistically significant in trials that did not randomise participants to an inhaled corticosteroid, but not when formoterol or salmeterol was combined with an inhaled corticosteroid. The confidence intervals were found to be too wide to ensure that the addition of an inhaled corticosteroid renders regular long-acting beta₂-agonists completely safe; few participants and insufficient serious adverse events in these trials precluded a definitive decision about the safety of combination treatments.
OBJECTIVES
To assess risks of mortality and non-fatal serious adverse events in trials that have randomised patients with chronic asthma to regular formoterol and an inhaled corticosteroid versus regular salmeterol and an inhaled corticosteroid.
SEARCH METHODS
We searched the Cochrane Airways Register of Trials, CENTRAL, MEDLINE, Embase, and two trial registries to identify reports of randomised trials for inclusion. We checked manufacturers' websites and clinical trial registers for unpublished trial data, as well as Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol. The date of the most recent search was 24 February 2021.
SELECTION CRITERIA
We included controlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma, if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid) and were of at least 12 weeks' duration.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion in the review, extracted outcome data from published papers and trial registries, and applied GRADE rating for the results. We sought unpublished data on mortality and serious adverse events from study sponsors and authors. The primary outcomes were all cause mortality and non-fatal serious adverse events. We chose not to calculate an average result from all the formulations of formoterol and inhaled steroid, as the doses and delivery devices are too diverse to assume a single class effect.
MAIN RESULTS
Twenty-one studies in 11,572 adults and adolescents and two studies in 723 children met the eligibility criteria of the review. No data were available for two studies; therefore these were not included in the analysis. Among adult and adolescent studies, seven compared formoterol and budesonide to salmeterol and fluticasone (N = 7764), six compared formoterol and beclomethasone to salmeterol and fluticasone (N = 1923), two compared formoterol and mometasone to salmeterol and fluticasone (N = 1126), two compared formoterol and fluticasone to salmeterol and fluticasone (N = 790), and one compared formoterol and budesonide to salmeterol and budesonide (N = 229). In total, five deaths were reported among adults, none of which was thought to be related to asthma. The certainty of evidence for all-cause mortality was low, as there were not enough deaths to permit any precise conclusions regarding the risk of mortality on combination formoterol versus combination salmeterol. In all, 201 adults reported non-fatal serious adverse events. In studies comparing formoterol and budesonide to salmeterol and fluticasone, there were 77 in the formoterol arm and 68 in the salmeterol arm (Peto odds ratio (OR) 1.14, 95% confidence interval (CI) 0.82 to 1.59; 5935 participants, 7 studies; moderate-certainty evidence). In the formoterol and beclomethasone studies, there were 12 adults in the formoterol arm and 13 in the salmeterol arm with events (Peto OR 0.94, 95% CI 0.43 to 2.08; 1941 participants, 6 studies; moderate-certainty evidence). In the formoterol and mometasone studies, there were 18 in the formoterol arm and 11 in the salmeterol arm (Peto OR 1.02, 95% CI 0.47 to 2.20; 1126 participants, 2 studies; moderate-certainty evidence). One adult in the formoterol and fluticasone studies in the salmeterol arm experienced an event (Peto OR 0.05, 95% CI 0.00 to 3.10; 293 participants, 2 studies; low-certainty evidence). Another adult in the formoterol and budesonide compared to salmeterol and budesonide study in the formoterol arm had an event (Peto OR 7.45, 95% CI 0.15 to 375.68; 229 participants, 1 study; low-certainty evidence). Only 46 adults were reported to have experienced asthma-related serious adverse events. The certainty of the evidence was low to very low due to the small number of events and the absence of independent assessment of causation. The two studies in children compared formoterol and fluticasone to salmeterol and fluticasone. No deaths and no asthma-related serious adverse events were reported in these studies. Four all-cause serious adverse events were reported: three in the formoterol arm, and one in the salmeterol arm (Peto OR 2.72, 95% CI 0.38 to 19.46; 548 participants, 2 studies; low-certainty evidence).
AUTHORS' CONCLUSIONS
Overall, for both adults and children, evidence is insufficient to show whether regular formoterol in combination with budesonide, beclomethasone, fluticasone, or mometasone has a different safety profile from salmeterol in combination with fluticasone or budesonide. Five deaths of any cause were reported across all studies and no deaths from asthma; this information is insufficient to permit any firm conclusions about the relative risks of mortality on combination formoterol in comparison to combination salmeterol inhalers. Evidence on all-cause non-fatal serious adverse events indicates that there is probably little to no difference between formoterol/budesonide and salmeterol/fluticasone inhalers. However events for the other formoterol combination inhalers were too few to allow conclusions. Only 46 non-fatal serious adverse events were thought to be asthma related; this small number in addition to the absence of independent outcome assessment means that we have very low confidence for this outcome. We found no evidence of safety issues that would affect the choice between salmeterol and formoterol combination inhalers used for regular maintenance therapy by adults and children with asthma.
Topics: Administration, Inhalation; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Beclomethasone; Bronchodilator Agents; Budesonide; Child; Chronic Disease; Drug Therapy, Combination; Fluticasone; Formoterol Fumarate; Glucocorticoids; Humans; Mometasone Furoate; Randomized Controlled Trials as Topic; Salmeterol Xinafoate
PubMed: 33852162
DOI: 10.1002/14651858.CD007694.pub3