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Annals of the Rheumatic Diseases Jan 2021Janus kinase inhibitors (JAKi) have been approved for use in various immune-mediated inflammatory diseases. With five agents licensed, it was timely to summarise the...
OBJECTIVES
Janus kinase inhibitors (JAKi) have been approved for use in various immune-mediated inflammatory diseases. With five agents licensed, it was timely to summarise the current understanding of JAKi use based on a systematic literature review (SLR) on efficacy and safety.
METHODS
Existing data were evaluated by a steering committee and subsequently reviewed by a 29 person expert committee leading to the formulation of a consensus statement that may assist the clinicians, patients and other stakeholders once the decision is made to commence a JAKi. The committee included patients, rheumatologists, a gastroenterologist, a haematologist, a dermatologist, an infectious disease specialist and a health professional. The SLR informed the Task Force on controlled and open clinical trials, registry data, phase 4 trials and meta-analyses. In addition, approval of new compounds by, and warnings from regulators that were issued after the end of the SLR search date were taken into consideration.
RESULTS
The Task Force agreed on and developed four general principles and a total of 26 points for consideration which were grouped into six areas addressing indications, treatment dose and comedication, contraindications, pretreatment screening and risks, laboratory and clinical follow-up examinations, and adverse events. Levels of evidence and strengths of recommendations were determined based on the SLR and levels of agreement were voted on for every point, reaching a range between 8.8 and 9.9 on a 10-point scale.
CONCLUSION
The consensus provides an assessment of evidence for efficacy and safety of an important therapeutic class with guidance on issues of practical management.
Topics: Adamantane; Advisory Committees; Antirheumatic Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Azetidines; Cytokines; Drug Therapy, Combination; Europe; Heterocyclic Compounds, 3-Ring; Humans; Inflammatory Bowel Diseases; Janus Kinase Inhibitors; Niacinamide; Piperidines; Psoriasis; Purines; Pyrazoles; Pyridines; Pyrimidines; Rheumatology; Spondylarthropathies; Spondylitis, Ankylosing; Sulfonamides; Triazoles
PubMed: 33158881
DOI: 10.1136/annrheumdis-2020-218398 -
Journal of Managed Care & Specialty... Sep 2021Insomnia is a common disorder associated with a substantial burden of illness, particularly in older adults. To compare the efficacy and safety of lemborexant with... (Comparative Study)
Comparative Study Meta-Analysis
Insomnia is a common disorder associated with a substantial burden of illness, particularly in older adults. To compare the efficacy and safety of lemborexant with specified other insomnia treatments through a systematic literature review and network meta-analysis (NMA). Medline and Embase were systematically searched from inception to February 2019 and updated with a targeted search of PubMed for pivotal trials in March 2021. Randomized controlled trials in adults with primary insomnia were included if they reported results following at least 1 week of treatment. Interventions of interest were specified as lemborexant, suvorexant, benzodiazepines, benzodiazepine receptor agonists (also called Z-drugs [zolpidem, eszopiclone, zaleplon, zopiclone]), trazodone, and ramelteon. Efficacy outcomes included wake after sleep onset (WASO), sleep efficiency (SE), latency to persistent sleep (LPS)/sleep onset latency (SOL), total sleep time (TST) and Insomnia Severity Index (ISI). Bayesian NMA were performed at predetermined time intervals approximating 4 weeks, 3 months, and 6 months. Safety outcomes included serious adverse events (SAEs), withdrawals due to adverse events (AEs), and specified AEs (dizziness, somnolence, and falls). Subgroup analysis was conducted in the older population. 45 studies were included in the NMA. At 4 weeks, lemborexant had the highest probability of being the best treatment for 3 of the 4 outcomes measured objectively by polysomnography-TST, LPS, and SE-and was ranked second to suvorexant on WASO. Eszopiclone was highly ranked for subjectively measured SOL and ISI at 4 weeks, 3 months, and 6 months. Lemborexant was rated more highly than suvorexant in subjective measures of WASO, TST, and SOL at 4 weeks (the differences were not statistically significant). No statistically significant interactions between treatment effect and older subpopulations were found, indicating that the treatment effect was similar in older and adult populations. The safety profile of lemborexant was broadly similar to the other treatments for SAEs and withdrawals due to AEs. A limitation is the age of some of the included studies (3 were published in 1990 or earlier). A further limitation is the lack of stratification of recommended doses. If the doses used in the study publications do not reflect doses used in clinical practice, this could potentially bias the results. Lemborexant was ranked highest of the treatments studied on 3 out of the 4 objectively measured insomnia efficacy outcomes, with a safety profile broadly similar to other insomnia treatments. This work was funded by Eisai Inc., which was involved with all stages of the study and analysis. McElroy, O'Leary, and Adena are consultants with Datalytics Pty Ltd., which was paid by Eisai Inc. for conducting the literature review and analysis. They were not financially compensated for collaborative efforts on publication-related activities. Campbell, Tahami Monfared, and Meier are employed by Eisai Inc. This study was presented as a poster at AMCP Nexus Virtual, October 20-23, 2020 and at the AGS Virtual Annual Scientific Meeting 2021, May 13-15, 2021.
Topics: Humans; Orexin Receptor Antagonists; Pyridines; Pyrimidines; Sleep Initiation and Maintenance Disorders; Treatment Outcome
PubMed: 34121443
DOI: 10.18553/jmcp.2021.21011 -
Experimental Gerontology Apr 2020Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that is present in all living cells. NAD+ acts as an important cofactor and substrate for a...
Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that is present in all living cells. NAD+ acts as an important cofactor and substrate for a multitude of biological processes including energy production, DNA repair, gene expression, calcium-dependent secondary messenger signalling and immunoregulatory roles. The de novo synthesis of NAD+ is primarily dependent on the kynurenine pathway (KP), although NAD+ can also be recycled from nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR). NAD+ levels have been reported to decline during ageing and age-related diseases. Recent studies have shown that raising intracellular NAD+ levels represents a promising therapeutic strategy for age-associated degenerative diseases in general and to extend lifespan in small animal models. A systematic review of the literature available on Medline, Embase and Pubmed was undertaken to evaluate the potential health and/or longevity benefits due to increasing NAD+ levels. A total of 1545 articles were identified and 147 articles (113 preclinical and 34 clinical) met criteria for inclusion. Most studies indicated that the NAD+ precursors NAM, NR, nicotinamide mononucleotide (NMN), and to a lesser extent NAD+ and NADH had a favourable outcome on several age-related disorders associated with the accumulation of chronic oxidative stress, inflammation and impaired mitochondrial function. While these compounds presented with a limited acute toxicity profile, evidence is still quite limited and long-term human clinical trials are still nascent in the current literature. Potential risks in raising NAD+ levels in various clinical disorders using NAD+ precursors include the accumulation of putative toxic metabolites, tumorigenesis and promotion of cellular senescence. Therefore, NAD+ metabolism represents a promising target and further studies are needed to recapitulate the preclinical benefits in human clinical trials.
Topics: Aging; Animals; Humans; Inflammation; Mice; NAD; Neurodegenerative Diseases; Niacinamide; Nicotinamide Mononucleotide; Oxidative Stress; Pyridinium Compounds; Rats; Risk Assessment
PubMed: 31917996
DOI: 10.1016/j.exger.2020.110831 -
The American Journal of Medicine Aug 2023People who smoke conventional cigarettes are increasingly turning to electronic cigarettes (e-cigarettes) as a pathway to quitting. However, the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
People who smoke conventional cigarettes are increasingly turning to electronic cigarettes (e-cigarettes) as a pathway to quitting. However, the efficacy and safety of e-cigarettes for smoking cessation remains controversial.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), identified through a systematic search of the MEDLINE, EMBASE, and Cochrane CENTRAL databases. Inclusion was restricted to RCTs with a follow-up duration ≥6 months. The primary endpoint was the most rigorous criterion of biochemically validated abstinence at maximum follow-up, and the primary comparison was nicotine e-cigarettes versus any conventional (ie, non-e-cigarette) smoking cessation therapy. The Cochrane Risk of Bias Tool was used to assess bias. Count data were pooled across trials using random-effects models with inverse variance weighting to estimate relative risks (RRs) and corresponding 95% confidence intervals (CIs). We registered the study protocol with the Open Science Framework Registries (osf.io/26fkq).
RESULTS
A total of 5 RCTs (n = 3253) were included. Compared with conventional smoking cessation therapies, the use of nicotine e-cigarettes was associated with an increase in abstinence, defined by the most rigorous criterion of abstinence reported (RR 1.77; 95% CI, 1.29-2.44). Nicotine e-cigarettes also increased abstinence (defined by the most rigorous criterion) compared with non-nicotine e-cigarettes (RR 1.56; 95% CI, 1.13-2.15). The incidence of death or serious adverse events was low across all trials at maximum follow-up.
CONCLUSIONS
Among individuals attempting to quit smoking, nicotine e-cigarettes are more efficacious than conventional nicotine replacement or behavioral smoking cessation therapies, and may prove beneficial in reducing smoking-related health risks.
Topics: Humans; Smoking Cessation; Nicotinic Agonists; Vaping; Tobacco Use Cessation Devices; Randomized Controlled Trials as Topic; Nicotine; Electronic Nicotine Delivery Systems
PubMed: 37148992
DOI: 10.1016/j.amjmed.2023.04.014 -
Archives of Gynecology and Obstetrics Oct 2023Nausea and vomiting during pregnancy (NVP) are common symptoms in pregnancy. Although no definitive treatment option for NVP, pyridoxine (Vitamin B6) supplementation has... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Nausea and vomiting during pregnancy (NVP) are common symptoms in pregnancy. Although no definitive treatment option for NVP, pyridoxine (Vitamin B6) supplementation has been used widely. The present study aims to systematically evaluate the current evidence regarding pyridoxine for the treatment of NVP.
METHODS
Data were obtained using a stepwise search process using keywords in the following online medical databases; PubMed, Web of Science, and Scopus for studies published before 1st May 2021. Studies reporting intervention with pyridoxine supplementation alone and/or with other active substances were included. A meta-analysis was performed on the PUQE score and Rhode's score for nausea and vomiting.
FINDINGS
Initial database searching indicated 548 potentially eligible articles, of which 18 studies satisfying the inclusion criteria were selected. Eight studies showed beneficial effects with pyridoxine alone as the supplementation, while six others found that the supplementation of pyridoxine in combination with another active substance had favourable effects. Supplementation of pyridoxine alone as well as combined treatment of pyridoxine with an active ingredient as the intervention significantly improved the symptoms of nausea according to Rhode's score [0.78 [95% CI: 0.26, 1.31; p = 0.003; I2 = 57%, p = 0.10)] and PUQE score [0.75 (95% CI: 0.28, 1.22; p = 0.002; I2 = 0%, p = 0.51)], respectively.
CONCLUSION
Supplementation of pyridoxine alone as well as with an active ingredient demonstrated beneficial effects for women suffering from NVP.
Topics: Pregnancy; Female; Humans; Pyridoxine; Vitamin B 6; Vomiting; Nausea; Pregnancy Complications; Dietary Supplements; Antiemetics
PubMed: 36719452
DOI: 10.1007/s00404-023-06925-w -
Nutrients Jun 2023Vitamin B6 is a water-soluble vitamin that is naturally present in many foods and is accessible in many dietary supplements. The three natural forms are pyridoxine,... (Review)
Review
INTRODUCTION
Vitamin B6 is a water-soluble vitamin that is naturally present in many foods and is accessible in many dietary supplements. The three natural forms are pyridoxine, pyridoxal, and pyridoxamine. Both vitamin B6 deficiency and high B6 intake have been described as risk factors for developing peripheral neuropathy (PN). The aim of this systematic review is to characterize and comprehensively describe B6-related PN.
METHOD
A systematic, computer-based search was conducted using the PubMed database. Twenty articles were included in this review.
RESULTS
Higher vitamin B6 levels, which usually occur following the taking of nutritional supplements, may lead to the development of a predominantly, if not exclusively, sensory neuropathy of the axonal type. After pyridoxine discontinuation, such patients subjectively report improved symptoms. However, although low vitamin B6 levels can be seen in patients suffering from peripheral neuropathy of various etiologies, there is no firm evidence that low B6 levels have a direct causal relationship with PN. Many studies suggest subjective improvement of neuropathy symptoms in patients suffering from PN of various etiologies after receiving B6 supplementation; however, no data about B6 administration as a monotherapy exist, only as part of a combination treatment, usually with other vitamins. Therefore, the potential therapeutic role of B6 cannot be confirmed to date. Supplementation with vitamin B6, even as part of a nutritional multivitamin supplement, has not been proven harmful at permitted daily doses in patients who already suffer from PN.
CONCLUSION
Current scientific evidence supports a neurotoxic role of B6 at high levels. Although some studies suggest that low B6 is also a potential risk factor, further studies in this area are needed.
Topics: Humans; Pyridoxine; Vitamin B 6; Pyridoxal; Pyridoxamine; Vitamins; Peripheral Nervous System Diseases
PubMed: 37447150
DOI: 10.3390/nu15132823 -
Journal of Psychiatric Research Sep 2020We conducted a random-effects model network meta-analysis to examine differences between lemborexant and suvorexant in efficacy and safety outcomes for treating patients... (Meta-Analysis)
Meta-Analysis
We conducted a random-effects model network meta-analysis to examine differences between lemborexant and suvorexant in efficacy and safety outcomes for treating patients with insomnia. We searched Embase, MEDLINE, and CENTRAL from their inception until April/28/2020. Primary outcomes were subjective time to sleep onset (sTSO), subjective total sleep time (sTST), and subjective wake-after-sleep onset (sWASO) at week 1. Four double-blind, randomized controlled trials were identified (n = 3237; 72.4% female; mean age 58.0 years). The treatment arm consisted of lemborexant 10 mg/d (LEM10, n = 592), lemborexant 5 mg/d (LEM5, n = 589), suvorexant 20/15 mg/d (SUV20/15, n = 493), zolpidem tartrate extended release 6.25 mg/d (ZOL6.25, n = 263), and placebo (n = 1300). All active treatments outperformed placebo regarding sTSO at week 1; standardized mean differences (95% credible interval): LEM10 = -0.51 (-0.63, -0.39), LEM5 = -0.48 (-0.60, -0.36), SUV20/15 = -0.21 (-0.33, -0.10), and ZOL6.25 = -0.30 (-0.46, -0.14); sTST at week 1: LEM10 = -0.58 (-0.70, -0.45), LEM5 = -0.33 (-0.46, -0.21), SUV20/15 = -0.34 (-0.46, -0.23), and ZOL6.25 = -0.42 (-0.59, -0.25); and sWASO at week 1: LEM10 = -0.42 (-0.57, -0.28), LEM5 = -0.26 (-0.40, -0.11), SUV20/15 = -0.18 (-0.32, -0.05), and ZOL6.25 = -0.37 (-0.56, -0.18). Although no significant differences were found in discontinuation due to adverse events between each active drug and placebo, LEM10 and SUV20/15 were associated with greater somnolence compared with placebo. LEM10 had the largest effect size compared with placebo for all primary outcomes, although with a risk of somnolence.
Topics: Azepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Network Meta-Analysis; Pyridines; Pyrimidines; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Triazoles
PubMed: 32531478
DOI: 10.1016/j.jpsychires.2020.05.025 -
Heart Failure Reviews Jan 2021Diuretics have an essential role in the management of heart failure (HF). However, each drug has its own benefit and side effect. Side effects include fluid, electrolyte... (Meta-Analysis)
Meta-Analysis Review
Diuretics have an essential role in the management of heart failure (HF). However, each drug has its own benefit and side effect. Side effects include fluid, electrolyte abnormalities, and acid-base disturbance. These adverse effects of diuretics predispose patients to serious cardiac arrhythmias and may increase the risk of arrhythmic mortality. Herein, we aim to summarize the relative efficacy and safety of all available diuretics used in the treatment of patients with HF. In June 2017, a systematic electronic database search was conducted in nine databases. All randomized controlled trials (RCTs) comparing the different diuretics used in HF were included for meta-analysis. The protocol was registered in Prospero with CRD42018084819. Among the included 54 studies (10,740 patients), 34 RCTs were eligible for quantitative network meta-analysis (NMA) and traditional meta-analysis while the other 20 studies were qualitatively analyzed. Our results showed that azosemide and torasemide caused a significant reduction in brain natriuretic peptide (BNP) level. Torasemide also caused a significant decrease in collagen volume fraction (CVF) and edema. No significant difference between the agents concerning glomerular filtration rate (GFR), water extraction, and sodium excretion was demonstrated. Regarding side effects, no significant difference among diuretics was observed in terms of hospital readmission and mortality rates. Diuretics are the main treatment of hypervolemia in HF patients. The choice of appropriate diuretic is essential for successful management and is mainly guided by patient clinical situations and the presence of other co-morbidities.
Topics: Diuretics; Furosemide; Heart Failure; Humans; Randomized Controlled Trials as Topic; Torsemide
PubMed: 32783109
DOI: 10.1007/s10741-020-10003-7 -
Annals of the American Thoracic Society Jun 2022The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax convened to update clinical... (Meta-Analysis)
Meta-Analysis
The American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax convened to update clinical practice guidelines for interstitial lung disease (ILD). To conduct a systematic review to evaluate existing ILD literature to determine whether patients with progressive pulmonary fibrosis (PPF) should be treated with the antifibrotic pirfenidone. A literature search was conducted across MEDLINE, EMBASE, and Cochrane databases through December 2020 for studies using pirfenidone to treat patients with PPF. Mortality, disease progression, lung function, and adverse event data were extracted. Meta-analyses were performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation Working Group approach was used to assess the quality of evidence. Two studies met inclusion criteria. Meta-analyses revealed that changes in forced vital capacity (FVC) percent predicted (mean difference [MD], 2.3%; 95% confidence interval [CI], 0.5-4.1%), the FVC in milliliters (MD, 100.0 ml; 95% CI, 98.1-101.9 ml), and the 6-minute-walk distance in meters (MD, 25.2 m; 95% CI, 8.3-42.1 m) all favored pirfenidone over placebo. The changes in the diffusing capacity of the lung for carbon monoxide (DLCO) in millimoles per kilopascal per minute (MD, 0.40 mmol/kPa/min; 95%, CI 0.10-0.70 mmol/kPa/min) and risk of DLCO declining more than 15% (relative risk [RR], 0.27; 95% CI, 0.08-0.95) also favored pirfenidone. The risks of gastrointestinal discomfort (RR, 1.83; 95% CI, 1.29-2.60) and photosensitivity (RR, 4.88; 95% CI, 1.09-21.83) were higher with pirfenidone. The quality of the evidence was low or very low according to the Grading of Recommendations, Assessment, Development and Evaluation criteria, depending on the outcome. Pirfenidone use in patients with PPF is associated with a statistically significant decrease in disease progression and with protection of lung function. However, there is very low certainty in the estimated effects because of limitations in the available evidence. Funded by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.
Topics: Disease Progression; Humans; Lung Diseases, Interstitial; Pulmonary Fibrosis; Pyridones
PubMed: 35499847
DOI: 10.1513/AnnalsATS.202103-342OC -
The Cochrane Database of Systematic... May 2023Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting... (Review)
Review
BACKGROUND
Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). This is an update of a Cochrane Review first published in 2007.
OBJECTIVES
To assess the effectiveness of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group's Specialised Register in April 2022 for trials, using relevant terms in the title or abstract, or as keywords. The register is compiled from searches of CENTRAL, MEDLINE, Embase, and PsycINFO. SELECTION CRITERIA: We included randomised controlled trials that compared the treatment drug with placebo, another smoking cessation drug, e-cigarettes, or no medication. We excluded trials that did not report a minimum follow-up period of six months from baseline.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods. Our main outcome was abstinence from smoking at longest follow-up using the most rigorous definition of abstinence, preferring biochemically validated rates where reported. We pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model. We also reported the number of people reporting serious adverse events (SAEs).
MAIN RESULTS
We included 75 trials of 45,049 people; 45 were new for this update. We rated 22 at low risk of bias, 18 at high risk, and 35 at unclear risk. We found moderate-certainty evidence (limited by heterogeneity) that cytisine helps more people to quit smoking than placebo (RR 1.30, 95% confidence interval (CI) 1.15 to 1.47; I = 83%; 4 studies, 4623 participants), and no evidence of a difference in the number reporting SAEs (RR 1.04, 95% CI 0.78 to 1.37; I = 0%; 3 studies, 3781 participants; low-certainty evidence). SAE evidence was limited by imprecision. We found no data on neuropsychiatric or cardiac SAEs. We found high-certainty evidence that varenicline helps more people to quit than placebo (RR 2.32, 95% CI 2.15 to 2.51; I = 60%, 41 studies, 17,395 participants), and moderate-certainty evidence that people taking varenicline are more likely to report SAEs than those not taking it (RR 1.23, 95% CI 1.01 to 1.48; I = 0%; 26 studies, 14,356 participants). While point estimates suggested increased risk of cardiac SAEs (RR 1.20, 95% CI 0.79 to 1.84; I = 0%; 18 studies, 7151 participants; low-certainty evidence), and decreased risk of neuropsychiatric SAEs (RR 0.89, 95% CI 0.61 to 1.29; I = 0%; 22 studies, 7846 participants; low-certainty evidence), in both cases evidence was limited by imprecision, and confidence intervals were compatible with both benefit and harm. Pooled results from studies that randomised people to receive cytisine or varenicline showed that more people in the varenicline arm quit smoking (RR 0.83, 95% CI 0.66 to 1.05; I = 0%; 2 studies, 2131 participants; moderate-certainty evidence) and reported SAEs (RR 0.67, 95% CI 0.44 to 1.03; I = 45%; 2 studies, 2017 participants; low-certainty evidence). However, the evidence was limited by imprecision, and confidence intervals incorporated the potential for benefit from either cytisine or varenicline. We found no data on neuropsychiatric or cardiac SAEs. We found high-certainty evidence that varenicline helps more people to quit than bupropion (RR 1.36, 95% CI 1.25 to 1.49; I = 0%; 9 studies, 7560 participants), and no clear evidence of difference in rates of SAEs (RR 0.89, 95% CI 0.61 to 1.31; I = 0%; 5 studies, 5317 participants), neuropsychiatric SAEs (RR 1.05, 95% CI 0.16 to 7.04; I = 10%; 2 studies, 866 participants), or cardiac SAEs (RR 3.17, 95% CI 0.33 to 30.18; I = 0%; 2 studies, 866 participants). Evidence of harms was of low certainty, limited by imprecision. We found high-certainty evidence that varenicline helps more people to quit than a single form of nicotine replacement therapy (NRT) (RR 1.25, 95% CI 1.14 to 1.37; I = 28%; 11 studies, 7572 participants), and low-certainty evidence, limited by imprecision, of fewer reported SAEs (RR 0.70, 95% CI 0.50 to 0.99; I = 24%; 6 studies, 6535 participants). We found no data on neuropsychiatric or cardiac SAEs. We found no clear evidence of a difference in quit rates between varenicline and dual-form NRT (RR 1.02, 95% CI 0.87 to 1.20; I = 0%; 5 studies, 2344 participants; low-certainty evidence, downgraded because of imprecision). While pooled point estimates suggested increased risk of SAEs (RR 2.15, 95% CI 0.49 to 9.46; I = 0%; 4 studies, 1852 participants) and neuropsychiatric SAEs (RR 4.69, 95% CI 0.23 to 96.50; I not estimable as events only in 1 study; 2 studies, 764 participants), and reduced risk of cardiac SAEs (RR 0.32, 95% CI 0.01 to 7.88; I not estimable as events only in 1 study; 2 studies, 819 participants), in all three cases evidence was of low certainty and confidence intervals were very wide, encompassing both substantial harm and benefit.
AUTHORS' CONCLUSIONS
Cytisine and varenicline both help more people to quit smoking than placebo or no medication. Varenicline is more effective at helping people to quit smoking than bupropion, or a single form of NRT, and may be as or more effective than dual-form NRT. People taking varenicline are probably more likely to experience SAEs than those not taking it, and while there may be increased risk of cardiac SAEs and decreased risk of neuropsychiatric SAEs, evidence was compatible with both benefit and harm. Cytisine may lead to fewer people reporting SAEs than varenicline. Based on studies that directly compared cytisine and varenicline, there may be a benefit from varenicline for quitting smoking, however further evidence could strengthen this finding or demonstrate a benefit from cytisine. Future trials should test the effectiveness and safety of cytisine compared with varenicline and other pharmacotherapies, and should also test variations in dose and duration. There is limited benefit to be gained from more trials testing the effect of standard-dose varenicline compared with placebo for smoking cessation. Further trials on varenicline should test variations in dose and duration, and compare varenicline with e-cigarettes for smoking cessation.
Topics: Humans; Smoking Cessation; Nicotine; Varenicline; Bupropion; Electronic Nicotine Delivery Systems; Tobacco Use Cessation Devices; Nicotinic Agonists; Alkaloids
PubMed: 37142273
DOI: 10.1002/14651858.CD006103.pub8