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Frontiers in Immunology 2024While the association between vitamin D and several inflammatory biomarkers in asthma patients has been extensively reported, it remains unclear whether supplementation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
While the association between vitamin D and several inflammatory biomarkers in asthma patients has been extensively reported, it remains unclear whether supplementation modifies these biomarkers. This review aims to evaluate the impact of vitamin D supplementation on inflammatory biomarkers measured in individuals with asthma.
METHODS
We conducted a systematic review of randomized controlled trials (RCTs) published until November 2022 in six electronic databases evaluating the impact of vitamin D supplementation (any dose, form, administration route, frequency, or duration) compared to placebo in children or adults. The two co-primary outcomes were serum IgE and blood eosinophils reported at the endpoint. Secondary outcomes included other markers of type 2 inflammation (e.g., sputum eosinophils, fractional exhaled nitric oxide, etc.), anti-inflammatory biomarkers (e.g., interleukin (IL)-10, etc.), markers of non-type 2 inflammation (e.g., high-sensitivity C-reactive protein, etc.), and non-specific biomarkers (e.g., macrophages, etc.). Data were aggregated using fixed or random effect models.
RESULTS
Thirteen RCTs (5 in adults, 5 in pediatric patients, and 3 in mixed age groups) testing doses of vitamin D supplementation ranging from 800 to 400,000 IU over periods of 6 weeks to 12 months were included. Eight studies provided data on serum IgE and four on blood eosinophils. As secondary outcomes, three studies reported on sputum eosinophils, four on FeNO, five on serum IL-10, and two on airway IL-10. Compared to placebo, vitamin D supplementation had no significant effect on serum IgE (Mean difference [MD] [95% CI]: 0.06 [-0.13, 0.26] IU/mL), blood eosinophils (MD [95% CI]: - 0.02 [-0.11, 0.07] 10/μL), or FeNO (MD [95% CI]: -4.10 [-10.95, 2.75] ppb) at the endpoint. However, the vitamin D supplementation group showed higher serum IL-10 levels compared to placebo (MD [95% CI]: 18.85 [1.11, 36.59] pg/ml) at the endpoint. Although data could not be aggregated, narrative synthesis suggested no significant effect of supplementation on sputum eosinophils and IL-10 in both sputum and exhaled breath condensate, at the endpoint.
CONCLUSION
Vitamin D supplementation in individuals with asthma was not associated with lower inflammatory biomarkers related to type 2 inflammation. However, it was significantly associated with higher serum IL-10 compared to placebo.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022365666.
Topics: Adult; Humans; Child; Interleukin-10; Randomized Controlled Trials as Topic; Vitamin D; Vitamins; Asthma; Biomarkers; Inflammation; Immunoglobulin E; Dietary Supplements
PubMed: 38545098
DOI: 10.3389/fimmu.2024.1335968 -
Diseases (Basel, Switzerland) Feb 2024Plasma collected from people recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first antibody-based therapy employed to fight the pandemic. CCP was,... (Review)
Review
Safety and Efficacy of Convalescent Plasma Combined with Other Pharmaceutical Agents for Treatment of COVID-19 in Hospitalized Patients: A Systematic Review and Meta-Analysis.
Plasma collected from people recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first antibody-based therapy employed to fight the pandemic. CCP was, however, often employed in combination with other drugs, such as the antiviral remdesivir and glucocorticoids. The possible effect of such interaction has never been investigated systematically. To assess the safety and efficacy of CCP combined with other agents for treatment of patients hospitalized for COVID-19, a systematic literature search using appropriate Medical Subject Heading (MeSH) terms was performed through PubMed, EMBASE, Cochrane central, medRxiv and bioRxiv. The main outcomes considered were mortality and safety of CCP combined with other treatments versus CCP alone. This review was carried out in accordance with Cochrane methodology including risk of bias assessment and grading of the quality of evidence. Measure of treatment effect was the risk ratio (RR) together with 95% confidence intervals (CIs). A total of 11 studies (8 randomized controlled trials [RCTs] and 3 observational) were included in the systematic review, 4 studies with CCP combined with remdesivir and 6 studies with CCP combined with corticosteroids, all involving hospitalized patients. One RCT reported information on both remdesivir and steroids use with CCP. The use of CCP combined with remdesivir was associated with a significantly reduced risk of death (RR 0.74; 95% CI 0.56-0.97; = 0.03; moderate certainty of evidence), while the use of steroids with CCP did not modify the mortality risk (RR 0.72; 95% CI 0.34-1.51; = 0.38; very low certainty of evidence). Not enough safety data were retrieved form the systematic literature analysis. The current evidence from the literature suggests a potential beneficial effect on mortality of combined CCP plus remdesivir compared to CCP alone in hospitalized COVID-19 patients. No significant clinical interaction was found between CCP and steroids.
PubMed: 38534965
DOI: 10.3390/diseases12030041 -
The Cochrane Database of Systematic... Mar 2024Cardiovascular diseases (CVDs) are the leading cause of death globally, accounting for almost 18 million deaths annually. People with CVDs have a five times greater... (Review)
Review
BACKGROUND
Cardiovascular diseases (CVDs) are the leading cause of death globally, accounting for almost 18 million deaths annually. People with CVDs have a five times greater chance of suffering a recurrent cardiovascular event than people without known CVDs. Although drug interventions have been shown to be cost-effective in reducing the risk of recurrent cardiovascular events, adherence to medication remains suboptimal. As a scalable and cost-effective approach, mobile phone text messaging presents an opportunity to convey health information, deliver electronic reminders, and encourage behaviour change. However, it is uncertain whether text messaging can improve medication adherence and clinical outcomes. This is an update of a Cochrane review published in 2017.
OBJECTIVES
To evaluate the benefits and harms of mobile phone text messaging for improving medication adherence in people with CVDs compared to usual care.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, four other databases, and two trial registers. We also checked the reference lists of all primary included studies and relevant systematic reviews and meta-analyses. The date of the latest search was 30 August 2023.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) with participants with established arterial occlusive events. We included trials investigating interventions using short message service (SMS) or multimedia messaging service (MMS) with the aim of improving adherence to medication for the secondary prevention of cardiovascular events. The comparator was usual care. We excluded cluster-RCTs and quasi-RCTs.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were medication adherence, fatal cardiovascular events, non-fatal cardiovascular events, and combined CVD event. Secondary outcomes were low-density lipoprotein cholesterol for the effect of statins, blood pressure for antihypertensive drugs, heart rate for the effect of beta-blockers, urinary 11-dehydrothromboxane B2 for the antiplatelet effects of aspirin, adverse effects, and patient-reported experience. We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We included 18 RCTs involving a total of 8136 participants with CVDs. We identified 11 new studies in the review update and seven studies in the previous version of the review. Participants had various CVDs including acute coronary syndrome, coronary heart disease, stroke, myocardial infarction, and angina. All studies were conducted in middle- and high-income countries, with no studies conducted in low-income countries. The mean age of participants was 53 to 64 years. Participants were recruited from hospitals or cardiac rehabilitation facilities. Follow-up ranged from one to 12 months. There was variation in the characteristics of text messages amongst studies (e.g. delivery method, frequency, theoretical grounding, content used, personalisation, and directionality). The content of text messages varied across studies, but generally included medication reminders and healthy lifestyle information such as diet, physical activity, and weight loss. Text messages offered advice, motivation, social support, and health education to promote behaviour changes and regular medication-taking. We assessed risk of bias for all studies as high, as all studies had at least one domain at unclear or high risk of bias. Medication adherence Due to different evaluation score systems and inconsistent definitions applied for the measurement of medication adherence, we did not conduct meta-analysis for medication adherence. Ten out of 18 studies showed a beneficial effect of mobile phone text messaging for medication adherence compared to usual care, whereas the other eight studies showed either a reduction or no difference in medication adherence with text messaging compared to usual care. Overall, the evidence is very uncertain about the effects of mobile phone text messaging for medication adherence when compared to usual care. Fatal cardiovascular events Text messaging may have little to no effect on fatal cardiovascular events compared to usual care (odds ratio 0.83, 95% confidence interval (CI) 0.47 to 1.45; 4 studies, 1654 participants; low-certainty evidence). Non-fatal cardiovascular events We found very low-certainty evidence that text messaging may have little to no effect on non-fatal cardiovascular events. Two studies reported non-fatal cardiovascular events, neither of which found evidence of a difference between groups. Combined CVD events We found very low-certainty evidence that text messaging may have little to no effect on combined CVD events. Only one study reported combined CVD events, and did not find evidence of a difference between groups. Low-density lipoprotein cholesterol Text messaging may have little to no effect on low-density lipoprotein cholesterol compared to usual care (mean difference (MD) -1.79 mg/dL, 95% CI -4.71 to 1.12; 8 studies, 4983 participants; very low-certainty evidence). Blood pressure Text messaging may have little to no effect on systolic blood pressure (MD -0.93 mmHg, 95% CI -3.55 to 1.69; 8 studies, 5173 participants; very low-certainty evidence) and diastolic blood pressure (MD -1.00 mmHg, 95% CI -2.49 to 0.50; 5 studies, 3137 participants; very low-certainty evidence) when compared to usual care. Heart rate Text messaging may have little to no effect on heart rate compared to usual care (MD -0.46 beats per minute, 95% CI -1.74 to 0.82; 4 studies, 2946 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Due to limited evidence, we are uncertain if text messaging reduces medication adherence, fatal and non-fatal cardiovascular events, and combined cardiovascular events in people with cardiovascular diseases when compared to usual care. Furthermore, text messaging may result in little or no effect on low-density lipoprotein cholesterol, blood pressure, and heart rate compared to usual care. The included studies were of low methodological quality, and no studies assessed the effects of text messaging in low-income countries or beyond the 12-month follow-up. Long-term and high-quality randomised trials are needed, particularly in low-income countries.
Topics: Humans; Middle Aged; Text Messaging; Cardiovascular Diseases; Secondary Prevention; Cell Phone; Cholesterol, LDL; Medication Adherence
PubMed: 38533994
DOI: 10.1002/14651858.CD011851.pub3 -
Journal of Diabetes Research 2024The Preferred Reporting Items for Systematic Reviews and Analysis checklist was used. A comprehensive literature search of the PubMed, Embase, and Cochrane Library... (Meta-Analysis)
Meta-Analysis Review
METHODS
The Preferred Reporting Items for Systematic Reviews and Analysis checklist was used. A comprehensive literature search of the PubMed, Embase, and Cochrane Library databases was conducted through August 2022 to assess the impact of probiotics on blood glucose, lipid, and inflammatory markers in adults with prediabetes. Data were pooled using a random effects model and were expressed as standardized mean differences (SMDs) and 95% confidence interval (CI). Heterogeneity was evaluated and quantified as .
RESULTS
Seven publications with a total of 550 patients were included in the meta-analysis. Probiotics were found to significantly reduce the levels of glycosylated hemoglobin (HbA1c) (SMD -0.44; 95% CI -0.84, -0.05; = 0.03; = 76.13%, < 0.001) and homeostatic model assessment of insulin resistance (HOMA-IR) (SMD -0.27; 95% CI -0.45, -0.09; < 0.001; = 0.50%, = 0.36) and improve the levels of high-density lipoprotein cholesterol (HDL) (SMD -8.94; 95% CI -14.91, -2.97; = 0.003; = 80.24%, < 0.001), when compared to the placebo group. However, no significant difference was observed in fasting blood glucose, insulin, total cholesterol, triglycerides, low-density lipoprotein cholesterol, interleukin-6, tumor necrosis factor-, and body mass index. Subgroup analyses showed that probiotics significantly reduced HbA1c in adults with prediabetes in Oceania, intervention duration of ≥3 months, and sample size <30.
CONCLUSIONS
Collectively, our meta-analysis revealed that probiotics had a significant impact on reducing the levels of HbA1c and HOMA-IR and improving the level of HDL in adults with prediabetes, which indicated a potential role in regulating blood glucose homeostasis. However, given the limited number of studies included in this analysis and the potential for bias, further large-scale, higher-quality randomized controlled trials are needed to confirm these findings. This trial is registered with CRD42022358379.
Topics: Humans; Blood Glucose; Prediabetic State; Glycated Hemoglobin; Probiotics; Homeostasis; Cholesterol; Insulin Resistance
PubMed: 38529045
DOI: 10.1155/2024/5996218 -
Cureus Feb 2024The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs)... (Review)
Review
The most recent advancements in cancer therapy center on efficiently and conveniently enhancing a patient's natural immune system. Immune checkpoint inhibitors (ICIs) are antibodies that target cytotoxic thymus (T) lymphocyte antigen-4 (CTLA-4) and its receptor. They function by stimulating T-cell activity against malignancies. Immune-related adverse events (irAEs) are a distinct class of inflammatory side effects that are specific to a given organ. Antineoplastic medications can impact any part of the kidney, leading to the development of proteinuria, hypertension, electrolyte abnormalities, glomerulonephritis, and both acute and chronic interstitial nephritis. We reviewed the scientific literature regarding kidney problems that can arise from chemotherapy and immunotherapy for neoplasms, such as various cancers, melanoma, non-small cell lung cancer, and colorectal cancer. We discussed the pathophysiology, associated risk factors, management, and safety measures for patients experiencing acute renal injury after a new immunotherapy medication treatment. Antineoplastic drugs have the potential to damage the renal tubules, glomeruli, parenchyma, and blood vessels, among other kidney tissues. This can result in a broad spectrum of complications, spanning from a rise in serum creatinine levels without symptoms to the development of acute kidney injury (AKI). The research examined a range of risk factors associated with acute kidney injury (AKI). These factors encompassed age, gender, preexisting medical conditions (such as diabetes, hypertension, and chronic kidney disease), and the medications that patients were taking at the beginning of the study, which included non-steroidal anti-inflammatory drugs, renin-angiotensin system inhibitors, allopurinol, diuretics, corticosteroids, and proton pump inhibitors. The data suggests that patients who were receiving baseline treatment with proton pump inhibitors (PPIs) or corticosteroids had a higher risk of mortality. This study serves as an illustration of the effective management of acute kidney injury and proteinuria linked to novel immunotherapy drugs like pembrolizumab. The approach involved the use of corticosteroids tailored to the patient's condition. Furthermore, it references the recommendations outlined in the Common Terminology Criteria for Adverse Events (CTCAE). Prompt recognition and effective management of these side effects are essential to optimizing outcomes for patients undergoing immunotherapy. Our results were refined and focused by utilizing Medical Subject Headings (MeSH) keywords in our search strategy. The MeSH keywords used were "renal side effects" OR "immunotherapy" OR "cancer treatment." The studies reviewed encompassed a total of 48,529 participants among the 21 studies examined.
PubMed: 38516472
DOI: 10.7759/cureus.54487 -
BMC Pediatrics Mar 2024Intravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). Higher doses of IVIg are associated with a... (Meta-Analysis)
Meta-Analysis
Can low-dose intravenous immunoglobulin be an alternative to high-dose intravenous immunoglobulin in the treatment of children with newly diagnosed immune thrombocytopenia: a systematic review and meta-analysis.
Intravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). Higher doses of IVIg are associated with a more insupportable financial burden to pediatric patients' families and may produce more adverse reactions. Whether low-dose IVIg (LD-IVIg) can replace high-dose IVIg (HD-IVIg) has yet to be established. We conducted a comprehensive literature search from the establishment of the database to May 1, 2023, and eventually included 22 RCTs and 3 cohort studies compared different dosages of IVIg. A total of 1989 patients were included, with 991 patients in the LD-IVIg group and 998 patients in the HD-IVIg group. Our results showed no significant differences between the two groups in the effective rate (LD-IVIg: 91% vs. HD-IVIg: 93%; RR: 0.99; 95%CI: 0.96-1.02) and the durable remission rate (LD-IVIg: 65% vs. HD-IVIg: 67%; RR: 0.97; 95%CI: 0.89-1.07). Similar results were also found in the time of platelet counts (PC) starting to rise (MD: 0.01, 95%CI: -0.06-0.09), rising to normal (MD: 0.16, 95%CI: -0.03-0.35), and achieving hemostasis (MD: 0.11, 95%CI: -0.02-0.23) between the two groups. Subgroup analysis showed the effective rate of 0.6 g/kg was equal to 1 g/kg subgroup (91%) but higher than 0.8 g/kg subgroup (82%), and a combination with glucocorticoid may contribute to effect enhancement (combined with glucocorticoid: 91% vs. IVIg alone: 86%) whether combined with dexamethasone (92%) or methylprednisolone (91%). Besides, the incidence rate of adverse reactions in the LD-IVIg group (3%) was significantly lower than the HD-IVIg group (6%) (RR: 0.61; 95%CI: 0.38-0.98). So low-dose IVIg (≤ 1 g/kg) is effective, safe, and economical, which can replace high-dose IVIg (2 g/kg) as an initial treatment. This systematic review was registered in PROSPERO (CRD42022384604).
Topics: Child; Humans; Purpura, Thrombocytopenic, Idiopathic; Immunoglobulins, Intravenous; Glucocorticoids; Platelet Count; Methylprednisolone
PubMed: 38515126
DOI: 10.1186/s12887-024-04677-3 -
Nutrition, Metabolism, and... May 2024Cardiovascular diseases (CVD) are the leading cause of death worldwide. Fasting is common in many religions and is associated with health benefits. This systematic... (Meta-Analysis)
Meta-Analysis
AIMS
Cardiovascular diseases (CVD) are the leading cause of death worldwide. Fasting is common in many religions and is associated with health benefits. This systematic review to compares the impact of different religious fasting practices, on risk of cardiometabolic diseases.
DATA SYNTHESIS
The search covered five databases following PRISMA guidelines to identify papers published in English from inception to March 2023 (updated January 2024). Inclusion criteria were healthy adults in observational studies, who engaged in religious fasting practices, studies were included where data on matched non-fasting individuals was available. Outcomes were systolic and diastolic blood pressure, body mass index (BMI), triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), and fasting plasma glucose levels. A meta-analysis was conducted, and the review was registered (CRD42022352197). Fourteen studies were met the inclusion criteria with ten studies data being suitable for meta-analysis, reporting on 755 adults participating in fasting practices and 661 non-fasting controls. Religious fasting was associated with a reduction in BMI (-0.40 kg/m, 95% CI [-0.70, -0.10], p < 0.01). Observance of Ramadan fasting was associated with decreased systolic blood pressure (-3.83 mmHg, 95% CI [-7.44, -0.23], p = 0.04). The observance of Orthodox Christian fasting was associated with a reduction in TC (-0.52 mmoL/l, 95%CI [-0.64, -0.39], p < 0.01). No difference was found for the other outcomes.
CONCLUSION
This review found religious fasting practices which were associated with a reduction in some biomarkers of cardiometabolic diseases risk. Further research on other fasting practices is needed due to limited data.
Topics: Adult; Humans; Cardiovascular Diseases; Cholesterol, HDL; Triglycerides; Cholesterol, LDL; Fasting; Risk Factors
PubMed: 38508992
DOI: 10.1016/j.numecd.2024.02.002 -
Cardiovascular Diabetology Mar 2024Randomized controlled trials and real-world studies suggest that combination therapy with sodium-glucose transport protein 2 inhibitors (SGLT2is) and glucagon-like... (Meta-Analysis)
Meta-Analysis
Effectiveness and safety of the combination of sodium-glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies.
BACKGROUND
Randomized controlled trials and real-world studies suggest that combination therapy with sodium-glucose transport protein 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is associated with improvement in fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), systolic blood pressure (SBP), body mass index (BMI), and total cholesterol levels. However, a systematic review of available real-world evidence may facilitate clinical decision-making in the real-world scenario. This meta-analysis assessed the safety and effectiveness of combinations of SGLT2is + GLP-1RAs with a focus on their cardioprotective effects along with glucose-lowering ability in patients with type 2 diabetes mellitus (T2DM) in a real-world setting.
METHODS
Electronic searches were performed in the PubMed/MEDLINE, PROQuest, Scopus, CINAHL, and Google Scholar databases. Qualitative analyses and meta-analyses were performed using the Joanna Briggs Institute SUMARI software package and Review Manager v5.4, respectively.
RESULTS
The initial database search yielded 1445 articles; of these, 13 were included in this study. The analyses indicated that SGLT2is + GLP-1RAs combinations were associated with significantly lower all-cause mortality when compared with individual therapies (odds ratio [95% confidence interval [CI] 0.49 [0.41, 0.60]; p < 0.00001). Significant reductions in BMI (- 1.71 [- 2.74, - 0.67]; p = 0.001), SBP (- 6.35 [- 10.17, - 2.53]; p = 0.001), HbA1c levels (- 1.48 [- 1.75, - 1.21]; p < 0.00001), and FPG (- 2.27 [- 2.78, - 1.76]; p < 0.00001) were associated with the simultaneous administration of the combination. Changes in total cholesterol levels and differences between simultaneous and sequential combination therapies for this outcome were not significant.
CONCLUSION
This systematic review and meta-analysis based on real-world data suggests that the combination of SGLT2is + GLP-1RAs is associated with lower all-cause mortality and favorable improvements in cardiovascular, renal, and glycemic measurements. The findings drive a call-to-action to incorporate this combination early and simultaneously in managing T2DM patients and achieve potential cardiovascular benefits and renal protection.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Glucagon-Like Peptide-1 Receptor Agonists; Glycated Hemoglobin; Blood Glucose; Cholesterol; Glucagon-Like Peptide-1 Receptor
PubMed: 38500154
DOI: 10.1186/s12933-024-02192-4 -
Annals of the Rheumatic Diseases May 2024New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the...
OBJECTIVE
New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA.
METHODS
Following EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts in April 2023. Levels of evidence and grades of recommendations were determined.
RESULTS
The updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and in the short term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drug (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase inhibitors is proposed primarily after bDMARD failure, taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices, with monoclonal tumour necrosis factor inhibitors proposed. Drug switches and tapering in sustained remission are also addressed.
CONCLUSION
These updated recommendations integrate all currently available drugs in a practical and progressive approach, which will be helpful in the pharmacological management of PsA.
Topics: Arthritis, Psoriatic; Humans; Antirheumatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Methotrexate; Biological Products
PubMed: 38499325
DOI: 10.1136/ard-2024-225531 -
Cancer Medicine Mar 2024Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin, angiotensin-converting enzyme [ACE] inhibitors, statins, and metformin) approved to treat diseases such as hypertension, hyperlipidemia, and diabetes mellitus to the field of oncology. Moreover, given growing costs with cancer care, these medications have offered a potentially more affordable avenue to treat or prevent recurrence of cancer. We sought to investigate the anti-cancer effects of drugs repurposed from cardiology or anti-inflammatories to treat cancer. We specifically evaluated the following drug classes: HMG-CoA reductase inhibitors (statins), cyclo-oxygenase inhibitors, aspirin, metformin, and both angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors. We also included non-steroidal anti-inflammatory drugs (NSAIDs) because they exert a similar mechanism to aspirin by blocking prostaglandins and reducing inflammation that is thought to promote the development of cancer.
METHODS
We performed a systematic literature review using PubMed and Web of Science with search terms including "aspirin," "NSAID," "statin" (including specific statin drug names), "metformin," "ACE inhibitors," and "ARBs" (including specific anti-hypertensive drug names) in combination with "cancer." Searches were limited to human studies published between 2000 and 2023.
MAIN OUTCOMES AND MEASURES
The number and percentage of studies reported positive results and pooled estimates of overall survival, progression-free survival, response, and disease-free survival.
RESULTS
We reviewed 3094 titles and included 67 randomized clinical trials. The most common drugs that were tested were metformin (n = 21; 30.9%), celecoxib (n = 20; 29.4%), and simvastatin (n = 8; 11.8%). There was only one study that tested cardiac glycosides and none that studied ACE inhibitors. The most common tumor types were non-small-cell lung cancer (n = 19; 27.9%); breast (n = 8; 20.6%), colorectal (n = 7; 10.3%), and hepatocellular (n = 6; 8.8%). Most studies were conducted in a phase II trial (n = 38; 55.9%). Most studies were tested in metastatic cancers (n = 49; 72.1%) and in the first-line setting (n = 36; 521.9%). Four studies (5.9%) were stopped early because of difficulty with accrual. The majority of studies did not demonstrate an improvement in either progression-free survival (86.1% of studies testing progression-free survival) or in overall survival (94.3% of studies testing overall survival). Progression-free survival was improved in five studies (7.4%), and overall survival was improved in three studies (4.4%). Overall survival was significantly worse in two studies (3.8% of studies testing overall survival), and progression-free survival was worse in one study (2.8% of studies testing progression-free survival).
CONCLUSIONS AND RELEVANCE
Despite promising pre-clinical and population-based data, cardiovascular drugs and anti-inflammatory medications have overall not demonstrated benefit in the treatment or preventing recurrence of cancer. These findings may help guide future potential clinical trials involving these medications when applied in oncology.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Carcinoma, Non-Small-Cell Lung; Angiotensin Receptor Antagonists; Lung Neoplasms; Randomized Controlled Trials as Topic; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents; Aspirin; Antihypertensive Agents; Metformin
PubMed: 38491813
DOI: 10.1002/cam4.7049