-
Drug Safety Mar 2021Antidepressant use during the first trimester is reported in 4-8% of pregnancies. The use of some selective serotonin reuptake inhibitors during the first trimester has... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Antidepressant use during the first trimester is reported in 4-8% of pregnancies. The use of some selective serotonin reuptake inhibitors during the first trimester has been identified as increasing the odds for congenital heart defects; however, little is known about the safety of non-selective serotonin reuptake inhibitor antidepressants.
OBJECTIVE
The objective of this study was to assess the odds of congenital heart defects associated with the use of antidepressants during the first trimester of pregnancy, and to update the literature as newer studies have been published since the latest systematic literature review and meta-analysis.
METHODS
PubMed and Embase were searched till 3 June, 2020. Study quality was assessed, and study details were extracted. Meta-analyses were performed using RevMan 5.4, which assessed: (1) any antidepressant usage; (2) classes of antidepressants; and (3) individual antidepressants.
RESULTS
Twenty studies were identified, encompassing 5,337,223 pregnancies. The odds ratio for maternal use of any antidepressant during the first trimester of pregnancy and the presence of congenital heart defects from the random effects meta-analysis was 1.28 (95% confidence interval [CI] 1.17-1.41). Significant odds ratios of 1.69 (95% CI 1.37-2.10) and 1.25 (95% CI 1.15-1.37) were reported for serotonin norepinephrine reuptake inhibitors and selective serotonin reuptake inhibitors, respectively. A non-statistically significant odds ratio of 1.02 (95% CI 0.82-1.25) was reported for the tricyclic antidepressants. Analyses of individual SSRIs produced significant odds ratios of 1.57 (95% CI 1.25-1.97), 1.36 (95% CI 1.08-1.72), and 1.29 (95% CI 1.14-1.45) for paroxetine, fluoxetine, and sertraline, respectively. The norepinephrine-dopamine-reuptake inhibitor bupropion also produced a significant odds ratio of 1.23 (95% CI 1.01-1.49).
CONCLUSIONS
The selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor classes of antidepressants pose a greater risk for causing congenital heart defects than the tricyclic antidepressants. However, this risk for individual antidepressants within each class varies, and information regarding some antidepressants is still lacking.
Topics: Antidepressive Agents; Antidepressive Agents, Tricyclic; Female; Heart Defects, Congenital; Humans; Norepinephrine; Pregnancy; Serotonin; Selective Serotonin Reuptake Inhibitors
PubMed: 33354752
DOI: 10.1007/s40264-020-01027-x -
Neuroscience and Biobehavioral Reviews Jan 2021Pupillometry, measuring pupil size and reactivity, has been proposed as a measure of autonomic nervous system functioning, the latter which might be altered in... (Meta-Analysis)
Meta-Analysis Review
Pupillometry, measuring pupil size and reactivity, has been proposed as a measure of autonomic nervous system functioning, the latter which might be altered in individuals with autism spectrum disorder (ASD). This study aims to evaluate if pupillary responses differ in individuals with and without ASD. After performing a systematic literature search, we conducted a meta-analysis and constructed a qualitative synthesis. The meta-analysis shows a longer latency of the pupil response in the ASD-group as a substantial group difference, with a Hedges' g of 1.03 (95% CI 0.49-1.56, p = 0.008). Evidence on baseline pupil size and amplitude change is conflicting. We used the framework method to perform a qualitative evaluation of these differences. Explanations for the group differences vary between studies and are inconclusive, but many authors point to involvement of the autonomous nervous system and more specifically the locus coeruleus-norepinephrine system. Pupillometry reveals differences between people with and without ASD, but the exact meaning of these differences remains unknown. Future studies should align research designs and investigate a possible effect of maturation.
Topics: Attention; Autism Spectrum Disorder; Humans; Locus Coeruleus; Norepinephrine
PubMed: 33172600
DOI: 10.1016/j.neubiorev.2020.09.032 -
Psychological Medicine Jul 2023Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) show similar efficacy as treatments for anxiety,... (Meta-Analysis)
Meta-Analysis Review
Incidence of adverse events and comparative tolerability of selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors for the treatment of anxiety, obsessive-compulsive, and stress disorders: a systematic review and network meta-analysis.
Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) show similar efficacy as treatments for anxiety, obsessive-compulsive, and stress-related disorders. Hence, comparisons of adverse event rates across medications are an essential component of clinical decision-making. We aimed to compare patterns of adverse events associated with SSRIs and SNRIs in the treatment of children and adults diagnosed with these disorders through a network meta-analysis. We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies, and international registers from inception to 09 September 2022, for randomized controlled trials assessing the efficacy of SSRIs or SNRIs. We analyzed the proportion of participants experiencing at least one adverse event and incidence rates of 17 specific adverse events. We estimated incidence rates and odds ratios through network meta-analysis with random effects and three-level models. We analyzed 799 outcome measures from 80 studies ( = 21 338). Participants in medication groups presented higher rates of adverse events (80.22%, 95% CI 76.13-83.76) when compared to placebo groups (71.21%, 67.00-75.09). Nausea was the most common adverse event (25.71%, CI 23.96-27.54), while weight change was the least common (3.56%, 1.68-7.37). We found higher rates of adverse events of medications over placebo for most medications, except sertraline and fluoxetine. We found significant differences between medications for overall tolerability and for autonomic, gastrointestinal, and sleep-related symptoms. Adverse events are a common reason that patients discontinue SSRIs and SNRIs. Results presented here guide clinical decision-making when clinicians weigh one medication over another. This might improve treatment acceptability and compliance.
Topics: Adult; Child; Humans; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Incidence; Norepinephrine; Serotonin; Network Meta-Analysis; Anxiety; Obsessive-Compulsive Disorder
PubMed: 37278215
DOI: 10.1017/S0033291723001630 -
The Journal of Arthroplasty Oct 2022Periarticular injection (PAI) is administered intraoperatively to help reduce postoperative pain and opioid consumption after primary total joint arthroplasty (TJA). The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Periarticular injection (PAI) is administered intraoperatively to help reduce postoperative pain and opioid consumption after primary total joint arthroplasty (TJA). The purpose of this study was to evaluate the efficacy and safety of PAI in primary TJA to support the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and American Society of Regional Anesthesia and Pain Medicine.
METHODS
The MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases were searched for studies published prior to March 2020 on PAI in TJA. All included studies underwent qualitative and quantitative homogeneity testing followed by a systematic review and direct comparison meta-analysis to assess the efficacy and safety of PAI.
RESULTS
Three thousand six hundred and ninety nine publications were critically appraised to provide 60 studies regarded as the best available evidence for an analysis. The meta-analysis showed that intraoperative PAI reduces postoperative pain and opioid consumption. Adding ketorolac or a corticosteroid to a long-acting local anesthetic (eg, ropivacaine or bupivacaine) provides an additional benefit. There is no difference between liposomal bupivacaine and other nonliposomal long-acting local anesthetics. Morphine does not provide any additive benefit in postoperative pain and opioid consumption and may increase postoperative nausea and vomiting. There is insufficient evidence to draw conclusions on the use of epinephrine and clonidine.
CONCLUSION
Strong evidence supports the use of a PAI with a long-acting local anesthetic to reduce postoperative pain and opioid consumption. Adding a corticosteroid and/or ketorolac to a long-acting local anesthetic further reduces postoperative pain and may reduce opioid consumption. Morphine has no additive effect and there is insufficient evidence on epinephrine and clonidine.
Topics: Analgesics, Opioid; Anesthetics, Local; Arthroplasty, Replacement, Knee; Bupivacaine; Clonidine; Epinephrine; Humans; Injections, Intra-Articular; Ketorolac; Morphine; Pain Management; Pain Measurement; Pain, Postoperative; Ropivacaine
PubMed: 36162925
DOI: 10.1016/j.arth.2022.03.045 -
International Journal of Chronic... 2023To evaluate the clinical efficacy and safety of bisoprolol in patients with chronic obstructive pulmonary disease (COPD). (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the clinical efficacy and safety of bisoprolol in patients with chronic obstructive pulmonary disease (COPD).
RESEARCH METHODS
This systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statements. The primary outcome measures analyzed included: Pulmonary function(FEV1, FEV1%, FVC), 6-minute walking distance (6MWD), adverse events and inflammatory cytokines(IL-6, IL-8, CRP).
RESULTS
Thirty-five studies were included with a total of 3269 study participants, including 1650 in the bisoprolol group and 1619 in the control group. The effect of bisoprolol on lung function in patients with COPD, FEV, MD (0.46 [95% CI, 0.27 to 0.65], P=0.000), FEV%, MD (-0.64 [95% CI, 0.42 to 0.86], P=0.000), FVC, MD (0.20 [95% CI, 0.05 to 0.34], P=0.008), the results all showed a statistically significant result. The effect of bisoprolol on 6MWD in COPD patients, MD (1.37 [95% CI, 1.08 to 1.66], P=0.000), which showed a statistically significant result. The occurrence of adverse events in COPD patients treated with bisoprolol, RR (0.83 [95% CI, 0.54 to 1.26], P=0.382), resulted in no statistical significance. The effect of bisoprolol on inflammatory cytokines in COPD patients, IL-6, MD (-1.16 [95% CI, -1.67 to -0.65], P=0.000), IL-8, MD (-0.94 [95% CI, -1.32 to -0.56], P=0.000), CRP, MD (-1.74 [95% CI, -2.40 to -1.09], P=0.000), the results were statistically significant. We performed a subgroup analysis of each outcome indicator according to whether the patients had heart failure or not, and the results showed that the therapeutic effect of bisoprolol on COPD did not change with the presence or absence of heart failure.
CONCLUSION
Bisoprolol is safe and effective in the treatment of COPD, improving lung function and exercise performance in patients with COPD, and also reducing inflammatory markers in patients with COPD, and this effect is independent of the presence or absence of heart failure.
Topics: Humans; Bisoprolol; Heart Failure; Interleukin-6; Interleukin-8; Pulmonary Disease, Chronic Obstructive; Quality of Life
PubMed: 38152590
DOI: 10.2147/COPD.S438930 -
The Quarterly Journal of Nuclear... Jun 2023Primary hyperparathyroidism (pHPT) is a common endocrine disorder caused by an autonomous overproduction of parathyroid hormone (PTH) by a parathyroid gland. Over the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Primary hyperparathyroidism (pHPT) is a common endocrine disorder caused by an autonomous overproduction of parathyroid hormone (PTH) by a parathyroid gland. Over the last decade, F-choline (FCH) PET has emerged as a highly performant imaging technique for guiding parathyroidectomy. As cure is the goal of surgery, the main aims of this study were to summarize patient-based sensitivity, positive predictive value (PPV), and cure rate of FCH PET guided surgery in the surgical management of pHPT.
EVIDENCE ACQUISITION
We conducted a systematic review and metaanalysis according to the PRISMA Guidelines. A literature search was performed in the PubMed, Web of Science and Cochrane databases, last updated November 2022. Original articles on choline PET in patients with pHPT mentioning patient-based sensitivity, PPV and cure rate were retained. Quality of included studies was assessed using the QUADAS-2 Tool. Patient-based sensitivity, PPV and cure rate were pooled by using a random-effects model.
EVIDENCE SYNTHESIS
Twenty-three studies including 1716 patients were included for quantitative assessment. FCH PET showed a pooled patient-based sensitivity of 93.8% (95% CI: 89.8-96.3) and PPV of 97% (95% CI: 92.8-98.8) in patients with pHPT. Parathyroid surgery was performed in 1129 patients. The pooled cure rate of PET-guided surgery was 92.8% (95% CI: 87.4-96.0). Heterogeneity was shown to be moderate for all effect sizes.
CONCLUSIONS
FCH PET showed a high patient-based sensitivity, PPV and cure rate of PET guided surgery in patients with pHPT.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Glands; Choline; Positron-Emission Tomography; Positron Emission Tomography Computed Tomography
PubMed: 36756935
DOI: 10.23736/S1824-4785.23.03512-4 -
JAMA Pediatrics Apr 2020Migraine is one of the most common neurologic disorders in children and adolescents. However, a quantitative comparison of multiple preventive pharmacologic treatments... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Migraine is one of the most common neurologic disorders in children and adolescents. However, a quantitative comparison of multiple preventive pharmacologic treatments in the pediatric population is lacking.
OBJECTIVE
To examine whether prophylactic pharmacologic treatments are more effective than placebo and whether there are differences between drugs regarding efficacy, safety, and acceptability.
DATA SOURCES
Systematic review and network meta-analysis of studies in MEDLINE, Cochrane, Embase, and PsycINFO published through July 2, 2018.
STUDY SELECTION
Randomized clinical trials of prophylactic pharmacologic treatments in children and adolescents diagnosed as having episodic migraine were included. Abstract, title, and full-text screening were conducted independently by 4 reviewers.
DATA EXTRACTION AND SYNTHESIS
Data extraction was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis network meta-analysis guidelines. Quality was assessed with the Cochrane Risk of Bias tool. Effect sizes, calculated as standardized mean differences for primary outcomes and risk ratios for discontinuation rates, were assessed in a random-effects model.
MAIN OUTCOMES AND MEASURES
Primary outcomes were efficacy (ie, migraine frequency, number of migraine days, number of headache days, headache frequency, or headache index), safety (ie, treatment discontinuation owing to adverse events), and acceptability (ie, treatment discontinuation for any reason).
RESULTS
Twenty-three studies (2217 patients) were eligible for inclusion. Prophylactic pharmacologic treatments included antiepileptics, antidepressants, calcium channel blockers, antihypertensive agents, and food supplements. In the short term (<5 months), propranolol (standard mean difference, 0.60; 95% CI, 0.03-1.17) and topiramate (standard mean difference, 0.59; 95% CI, 0.03-1.15) were significantly more effective than placebo. However, the 95% prediction intervals for these medications contained the null effect. No significant long-term effects for migraine prophylaxis relative to placebo were found for any intervention.
CONCLUSIONS AND RELEVANCE
Prophylactic pharmacologic treatments have little evidence supporting efficacy in pediatric migraine. Future research could (1) identify factors associated with individual responses to pharmacologic prophylaxis, (2) analyze fluctuations of migraine attack frequency over time and determine the most clinically relevant length of probable prophylactic treatment, and (3) identify nonpharmacologic targets for migraine prophylaxis.
Topics: Adolescent; Anticonvulsants; Antidepressive Agents; Antihypertensive Agents; Calcium Channel Blockers; Child; Dietary Supplements; Humans; Migraine Disorders; Propranolol; Topiramate; Vasodilator Agents
PubMed: 32040139
DOI: 10.1001/jamapediatrics.2019.5856 -
Journal of Oral Rehabilitation May 2021To synthesise and critically review the association between sleep bruxism (SB) and stress symptoms in adults. A systematic review was performed. The search was completed... (Meta-Analysis)
Meta-Analysis Review
To synthesise and critically review the association between sleep bruxism (SB) and stress symptoms in adults. A systematic review was performed. The search was completed using seven primary electronic databases in addition to a grey literature search. Two reviewers blindly selected studies based on pre-defined eligibility criteria. Risk of bias of the included articles was performed using the Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies. RevMan 5.4 was used to perform the meta-analysis. The quality of evidence was evaluated according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Ten studies were included for qualitative analysis, of which three were included for quantitative analysis. Three studies were evaluated to have low risk of bias, and seven were assessed with moderate risk of bias. Quality of evidence was classified as very low for all outcomes. Individuals with SB were found to have higher levels of some self-reported stress symptoms as assessed through questionnaires with a mean difference of 4.59 (95% CI 0.26-8.92). Biomarkers like epinephrine, norepinephrine, cortisol, adrenaline, dopamine, noradrenaline and prolidase enzyme levels also showed a positive association with SB. Although some associations were identified between probable SB and self-reported stress symptoms and biomarkers of stress in adults, given that the quality of evidence was found to be very low, caution should be exercised in interpreting these results. These findings suggest that additional and better designed studies are warranted in order to clarify the link between SB and stress.
Topics: Adult; Cross-Sectional Studies; Epinephrine; Humans; Self Report; Sleep Bruxism; Surveys and Questionnaires
PubMed: 33377534
DOI: 10.1111/joor.13142 -
The Cochrane Database of Systematic... Dec 2023Pompe disease is caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). People with infantile-onset disease have either a complete or a near-complete enzyme... (Review)
Review
BACKGROUND
Pompe disease is caused by a deficiency of the enzyme acid alpha-glucosidase (GAA). People with infantile-onset disease have either a complete or a near-complete enzyme deficiency; people with late-onset Pompe disease (LOPD) retain some residual enzyme activity. GAA deficiency is treated with an intravenous infusion of recombinant human acid alglucosidase alfa, an enzyme replacement therapy (ERT). Alglucosidase alfa and avalglucosidase alfa are approved treatments, but cipaglucosidase alfa with miglustat is not yet approved.
OBJECTIVES
To assess the effects of enzyme replacement therapies in people with late-onset Pompe disease.
SEARCH METHODS
We searched the Cochrane Inborn Errors of Metabolism Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched MEDLINE OvidSP, clinical trial registries, and the reference lists of relevant articles and reviews. Date of last search: 21 April 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of ERT in people with LOPD of any age.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial eligibility, extracted data, assessed the risk of bias and the certainty of the evidence (using GRADE). We resolved disagreements through discussion and by consulting a third author.
MAIN RESULTS
We included six trials (358 randomised participants) lasting from 12 to 78 weeks. A single trial reported on each comparison listed below. None of the included trials assessed two of our secondary outcomes: need for respiratory support and use of a walking aid or wheelchair. Certainty of evidence was most commonly downgraded for selective reporting bias. Alglucosidase alfa versus placebo (90 participants) After 78 weeks, alglucosidase alfa probably improves the six-minute walk test (6MWT) distance compared to placebo (mean difference (MD) 30.95 metres, 95% confidence interval (CI) 7.98 to 53.92; moderate-certainty evidence) and probably improves respiratory function, measured as the change in per cent (%) predicted forced vital capacity (FVC) (MD 3.55, 95% CI 1.46 to 5.64; moderate-certainty evidence). There may be little or no difference between the groups in occurrence of infusion reactions (risk ratio (RR) 1.21, 95% CI 0.57 to 2.61; low-certainty evidence), quality of life physical component score (MD -1.36 points, 95% CI -5.59 to 2.87; low-certainty evidence), or adverse events (RR 0.94, 95% CI 0.64 to 1.39; low-certainty evidence). Alglucosidase alfa plus clenbuterol versus alglucosidase alfa plus placebo (13 participants) The evidence is very uncertain about the effect of alglucosidase alfa plus clenbuterol compared to alglucosidase alfa plus placebo on: change in 6MWT distance after 52 weeks (MD 34.55 metres, 95% CI-10.11 to 79.21; very low-certainty evidence) and change in % predicted FVC (MD -13.51%, 95% CI -32.44 to 5.41; very low-certainty evidence). This study did not measure infusion reactions, quality of life, and adverse events. Alglucosidase alfa plus albuterol versus alglucosidase alfa plus placebo (13 participants) The evidence is very uncertain about the effect of alglucosidase alfa plus albuterol compared to alglucosidase alfa plus placebo on: change in 6MWT distance after 52 weeks (MD 30.00 metres, 95% CI 0.55 to 59.45; very low-certainty evidence), change in % predicted FVC (MD -4.30%, 95% CI -14.87 to 6.27; very low-certainty evidence), and risk of adverse events (RR 0.67, 95% CI 0.38 to 1.18; very low-certainty evidence). This study did not measure infusion reactions and quality of life. VAL-1221 versus alglucosidase alfa (12 participants) Insufficient information was available about this trial to generate effect estimates measured at one year or later. Compared to alglucosidase alfa, VAL-1221 may increase or reduce infusion-associated reactions at three months, but the evidence is very uncertain (RR 2.80, 95% CI 0.18 to 42.80). This study did not measure quality of life and adverse events. Cipaglucosidase alfa plus miglustat versus alglucosidase alfa plus placebo (125 participants) Compared to alglucosidase alfa plus placebo, cipaglucosidase alfa plus miglustat may make little or no difference to: 6MWT distance at 52 weeks (MD 13.60 metres, 95% CI -2.26 to 29.46); infusion reactions (RR 0.94, 95% CI 0.49 to 1.80); quality of life scores for physical function (MD 1.70, 95% CI -2.13 to 5.53) and fatigue (MD -0.30, 95% CI -2.76 to 2.16); and adverse effects potentially related to treatment (RR 0.83, 95% CI 0.49 to 1.40) (all low-certainty evidence). Cipaglucosidase alfa plus miglustat probably improves % predicted FVC compared to alglucosidase alfa plus placebo (MD 3.10%, 95% CI 1.04 to 5.16; moderate-certainty evidence); however, it may make little or no change in % predicted sniff nasal inspiratory pressure (MD -0.06%, 95% CI -8.91 to 7.71; low-certainty evidence). Avalglucosidase alfa versus alglucosidase alfa (100 participants) After 49 weeks, avalglucosidase alfa probably improves 6MWT compared to alglucosidase alfa (MD 30.02 metres, 95% CI 1.84 to 58.20; moderate-certainty evidence). Avalglucosidase alfa probably makes little or no difference to % predicted FVC compared to alglucosidase alfa (MD 2.43%, 95% CI -0.08 to 4.94; moderate-certainty evidence). Avalglucosidase alfa may make little or no difference to infusion reactions (RR 0.78, 95% CI 0.42 to 1.45), quality of life (MD 0.77, 95% CI -2.09 to 3.63), or treatment-related adverse events (RR 0.92, 95% CI 0.61 to 1.40), all low-certainty evidence.
AUTHORS' CONCLUSIONS
One trial compared the effect of ERT to placebo in LOPD, showing that alglucosidase alfa probably improves 6MWT and respiratory function (both moderate-certainty evidence). Avalglucosidase alfa probably improves 6MWT compared with alglucosidase alfa (moderate-certainty evidence). Cipaglucosidase plus miglustat probably improves FVC compared to alglucosidase alfa plus placebo (moderate-certainty evidence). Other trials studied the adjunct effect of clenbuterol and albuterol along with alglucosidase alfa, with little to no evidence of benefit. No significant rise in adverse events was noted with all ERTs. The impact of ERT on some outcomes remains unclear, and longer RCTs are needed to generate relevant information due to the progressive nature of LOPD. Alternative resources, such as post-marketing registries, could capture some of this information.
Topics: Humans; Glycogen Storage Disease Type II; Enzyme Replacement Therapy; Clenbuterol; Albuterol
PubMed: 38084761
DOI: 10.1002/14651858.CD012993.pub2 -
Advances in Therapy Jan 2023Short-acting β-agonist (SABA) reliever overuse is common in asthma, despite availability of inhaled corticosteroid (ICS)-based maintenance therapies, and may be... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Short-acting β-agonist (SABA) reliever overuse is common in asthma, despite availability of inhaled corticosteroid (ICS)-based maintenance therapies, and may be associated with increased risk of adverse events (AEs). This systematic literature review (SLR) and meta-analysis aimed to investigate the safety and tolerability of SABA reliever monotherapy for adults and adolescents with asthma, through analysis of randomized controlled trials (RCTs) and real-world evidence.
METHODS
An SLR of English-language publications between January 1996 and December 2021 included RCTs and observational studies of patients aged ≥ 12 years treated with inhaled SABA reliever monotherapy (fixed dose or as needed) for ≥ 4 weeks. Studies of terbutaline and fenoterol were excluded. Meta-analysis feasibility was dependent on cross-trial data comparability. A random-effects model estimated rates of mortality, serious AEs (SAEs), and discontinuation due to AEs (DAEs) for as-needed and fixed-dose SABA treatment groups. ICS monotherapy and SABA therapy were compared using a fixed-effects model.
RESULTS
Forty-two studies were identified by the SLR for assessment of feasibility. Final meta-analysis included 24 RCTs. Too few observational studies (n = 2) were available for inclusion in the meta-analysis. One death unrelated to treatment was reported in each of the ICS, ICS + LABA, and fixed-dose SABA groups. No other treatment-related deaths were reported. SAE and DAE rates were < 4%. DAEs were reported more frequently in the SABA treatment groups than with ICS, potentially owing to worsening asthma symptoms being classified as an AE. SAE risk was comparable between SABA and ICS treatments.
CONCLUSIONS
Meta-analysis of data from RCTs showed that deaths were rare with SABA reliever monotherapy, and rates of SAEs and DAEs were comparable between SABA reliever and ICS treatment groups. When used appropriately within prescribed limits as reliever therapy, SABA does not contribute to excess rates of mortality, SAEs, or DAEs.
Topics: Adult; Adolescent; Humans; Ethanolamines; Asthma; Terbutaline; Adrenal Cortex Hormones; Drug Therapy, Combination; Administration, Inhalation; Anti-Asthmatic Agents
PubMed: 36348141
DOI: 10.1007/s12325-022-02356-2