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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 -
Clinical and Translational Science Mar 2024The cardiovascular (CV) safety of febuxostat compared to allopurinol for the treatment of hyperuricemia among Asian patients is uncertain. In this study, we conducted a... (Meta-Analysis)
Meta-Analysis
The cardiovascular (CV) safety of febuxostat compared to allopurinol for the treatment of hyperuricemia among Asian patients is uncertain. In this study, we conducted a systematic review and meta-analysis to compare the CV safety profiles of febuxostat with allopurinol in Asian patients with hyperuricemia. A total of 13 studies were included. On the basis of the pooled results of cohort studies, febuxostat users were at a significantly higher risk for acute coronary syndrome (ACS; hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 1.03-1.09, p < 0.01), atrial fibrillation (HR: 1.19, 95% CI: 1.05-1.35, p < 0.01) than allopurinol users, whereas no significant difference between febuxostat and allopurinol existed for urgent coronary revascularization (HR: 1.07, 95% CI: 0.98-1.16, p = 0.13), and stroke (HR: 0.96, 95% CI: 0.91-1.01, p = 0.13). Nevertheless, that difference in results of acute decompensated heart failure (ADHF; HR: 0.73, 95% CI: 0.35-1.53, p = 0.40) and all-cause death (HR = 0.86, 95% CI: 0.49-1.51, p = 0.60) was not significant based on randomized controlled trials. In the Chinese subgroup, febuxostat could increase the risk of ADHF (HR: 1.22, 95% CI: 1.01-1.48, p < 0.05), CV death (HR: 1.25, 95% CI: 1.03-1.50, p < 0.05), and all-cause mortality (HR: 1.07, 95% CI: 1.01-1.14, p < 0.05) compared to allopurinol. In conclusion, the use of febuxostat, compared with allopurinol among Asian patients, was associated with a significantly increased risk of adverse CV events.
Topics: Humans; Allopurinol; Febuxostat; Hyperuricemia; Gout Suppressants; Cardiovascular Diseases; Gout; Treatment Outcome
PubMed: 38488426
DOI: 10.1111/cts.13757 -
PloS One 2024Colorectal adenomas have the potential of malignant transformation if left untreated. Multiple randomized controlled trials have been performed to evaluate the efficacy... (Meta-Analysis)
Meta-Analysis
Colorectal adenomas have the potential of malignant transformation if left untreated. Multiple randomized controlled trials have been performed to evaluate the efficacy of aspirin in preventing colorectal adenoma recurrence in a population with a history of colorectal adenoma but not colorectal cancer, however, the relationship between aspirin dose and colorectal adenoma recurrence remains unclear. We conducted pairwise meta-analysis, meta-regression, trial sequential analysis, and network meta-analysis of all eligible studies. The ROB 2.0 tool was used to assess the risk of bias in the studies. The confidence in network meta-analysis (CINeMA) approach was used to evaluate the confidence of the network meta-analysis results. The network meta-analysis included eight RCTs (nine reports), comprising four on aspirin (low or high dose) alone and four on aspirin combined with another medication, all compared with placebo. In the network meta-analysis, low-dose aspirin (LDA <300 mg per day) was more effective than high-dose aspirin (HDA ≥300 mg per day) and placebo, with risk ratios of 0.76 (95% CI: 0.58 to 0.99) and 0.7 (95% CI: 0.54 to 0.91), respectively. LDA was the optimal treatment relative to HDA and placebo (P-score = 0.99). In the trial sequential analysis, LDA was only more effective than placebo when the number of included participants exceeded the optimal information size; this was not the case for HDA. LDA has statistically significant efficacy for colorectal adenoma prevention, but compared with HDA, its efficacy remains uncertain. Further trials are therefore required.
Topics: Humans; Aspirin; Network Meta-Analysis; Randomized Controlled Trials as Topic; Colorectal Neoplasms; Adenoma
PubMed: 38483854
DOI: 10.1371/journal.pone.0279784 -
European Journal of Medical Research Mar 2024Granulomatous mastitis (GM) is a rare, benign, inflammatory breast disease with an unknown etiology that predominantly affects women of reproductive age. The definitive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Granulomatous mastitis (GM) is a rare, benign, inflammatory breast disease with an unknown etiology that predominantly affects women of reproductive age. The definitive treatment of GM is currently controversial; an appropriate therapeutic strategy has yet to be identified, and the disease's high recurrence rate remains. This study aims to determine the recurrence rate for each GM treatment strategy to identify the most appropriate treatment modality.
METHODS
The search for relevant articles was undertaken using three international databases, including Medline, Scopus, and Web of Science. Articles published in English until the end of 2021 evaluating the recurrence rate of GM were included. Using Stata 13.0, the pooled incidence and 95% confidence interval (CI) for the recurrence rate were determined.
RESULTS
Sixty-five eligible studies were included in our study. The recurrence rates of systemic steroid use, topical steroid use, antibiotic use, methotrexate use, observation, drainage, excision, antibiotic use and surgery, steroid use and surgery, antibiotic and steroid use, methotrexate and steroid use were 24% (95% CI: 21-27%), 11% (95% CI: 6-21%), 18% (95% CI: 14-22%), 13% (95% CI: 7-22%), 11% (95% CI: 7-17%), 65% (95% CI: 50-78%), 13% (95% CI: 10-16%), 23% (95% CI: 14-36%), 7% (95% CI: 5-11%), 11% (95% CI: 6-18%), and 4% (95% CI: 2-8%), respectively. Drainage had the highest recurrence rate, while combined methotrexate and steroid treatment had the lowest rate.
CONCLUSION
The optimal treatment strategy for GM depends on the disease's severity, consequences, and the patient's features. The study results indicate that combination therapy is preferable for minimizing the risk of relapse and reducing treatment complications.
Topics: Female; Humans; Granulomatous Mastitis; Methotrexate; Steroids; Combined Modality Therapy; Anti-Bacterial Agents; Recurrence
PubMed: 38475841
DOI: 10.1186/s40001-024-01761-3 -
International Journal of Molecular... Feb 2024Multiple sclerosis is a disabling inflammatory disorder of the central nervous system characterized by demyelination and neurodegeneration. Given that multiple sclerosis... (Review)
Review
Multiple sclerosis is a disabling inflammatory disorder of the central nervous system characterized by demyelination and neurodegeneration. Given that multiple sclerosis remains an incurable disease, the management of MS predominantly focuses on reducing relapses and decelerating the progression of both physical and cognitive decline. The continuous autoimmune process modulated by cytokines seems to be a vital contributing factor to the development and relapse of multiple sclerosis. This review sought to summarize the role of selected interleukins in the pathogenesis and advancement of MS. Patients with MS in the active disease phase seem to exhibit an increased serum level of IL-2, IL-4, IL-6, IL-13, IL-17, IL-21, IL-22 and IL-33 compared to healthy controls and patients in remission, while IL-10 appears to have a beneficial impact in preventing the progression of the disease. Despite being usually associated with proinflammatory activity, several studies have additionally recognized a neuroprotective role of IL-13, IL-22 and IL-33. Moreover, selected gene polymorphisms of IL-2R, IL-4, IL-6, IL-13 and IL-22 were identified as a possible risk factor related to MS development. Treatment strategies of multiple sclerosis that either target or utilize these cytokines seem rather promising, but more comprehensive research is necessary to gain a clearer understanding of how these cytokines precisely affect MS development and progression.
Topics: Humans; Cytokines; Interleukin-13; Interleukin-33; Interleukin-4; Interleukin-6; Interleukins; Multiple Sclerosis
PubMed: 38473835
DOI: 10.3390/ijms25052589 -
PLoS Neglected Tropical Diseases Mar 2024Human brucellosis is a neglected, re-emerging, and endemic zoonosis in many countries. The debilitating and disabling potential of the disease is a warning about its... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Human brucellosis is a neglected, re-emerging, and endemic zoonosis in many countries. The debilitating and disabling potential of the disease is a warning about its morbidity, generating socioeconomic impact. This review aims to update the current evidence on the efficacy and safety of therapeutic options for human brucellosis using the network meta-analysis (NMA).
METHODOLOGY
A systematic search was conducted in four different databases by independent reviewers to assess overall therapy failure, adverse events, and time to defervescence associated with different therapies. Randomized clinical trials (RCTs) evaluating any therapeutic drug intervention were selected, excluding non-original studies or studies related to localized forms of the disease or with less than 10 participants. Data were analyzed by frequentist statistics through NMA by random effects model. The risk of bias and certainty of evidence was assessed, this review was registered at PROSPERO.
RESULTS
Thirty-one (31) RCTs involving 4167 patients were included. Three networks of evidence were identified to evaluate the outcomes of interest. Triple therapy with doxycycline + streptomycin + hydroxychloroquine for 42 days (RR: 0.08; CI 95% 0.01-0.76) had a lower failure risk than the doxycycline + streptomycin regimen. Doxycycline + rifampicin had a higher risk of failure than doxycycline + streptomycin (RR: 1.96; CI 95% 1.27-3.01). No significant difference was observed between the regimens when analyzing the incidence of adverse events and time to defervescence. In general, most studies had a high risk of bias, and the results had a very low certainty of evidence.
CONCLUSIONS
This review confirmed the superiority of drugs already indicated for treating human brucellosis, such as the combination of doxycycline and aminoglycosides. The association of hydroxychloroquine to the dual regimen was identified as a potential strategy to prevent overall therapy failure, which is subject to confirmation in future studies.
Topics: Humans; Doxycycline; Network Meta-Analysis; Hydroxychloroquine; Brucellosis; Streptomycin
PubMed: 38466771
DOI: 10.1371/journal.pntd.0012010 -
Frontiers in Immunology 2024This study aimed to systematically compare the efficacy of various immunosuppressive agents in treating pediatric frequently relapsing or steroid-dependent nephrotic... (Meta-Analysis)
Meta-Analysis
AIM
This study aimed to systematically compare the efficacy of various immunosuppressive agents in treating pediatric frequently relapsing or steroid-dependent nephrotic syndrome (FRSDNS).
METHODS
We conducted systematic searches of PubMed, Embase, the Cochrane Library, and the Web of Science up to May 23, 2023. Outcome measures included relapses within 1 year, mean cumulative exposure to corticosteroids, patients with treatment failure at 1 year, relapse-free survival during 1 year, and adverse events. The quality of the included studies was evaluated using the modified Jadad scale, the Methodological Index for Non-Randomized Studies (MINORS), and the modified Newcastle-Ottawa Scale (NOS).
RESULTS
Rituximab was found to be the most likely (92.44%) to be associated with the fewest relapses within 1 year and was also most likely (99.99%) to result in the lowest mean cumulative exposure to corticosteroids. Rituximab had the highest likelihood (45.98%) of being associated with the smallest number of patients experiencing treatment failure at 1 year. CsA was most likely (57.93%) to achieve the highest relapse-free survival during 1 year, followed by tacrolimus (26.47%) and rituximab (30.48%). Rituximab showed no association with serious side effects and had comparable adverse effects to ofatumumab and tacrolimus.
CONCLUSION
Rituximab may be the most favorable immunosuppressive agent for treating pediatric FRSDNS. Nephrologists should consider this drug, along with their clinical experience, patient characteristics, and cost considerations, when choosing a treatment approach.
Topics: Child; Humans; Glucocorticoids; Immunosuppressive Agents; Nephrotic Syndrome; Network Meta-Analysis; Recurrence; Rituximab; Steroids; Tacrolimus
PubMed: 38464533
DOI: 10.3389/fimmu.2024.1310032 -
Journal of Cutaneous Medicine and... 2024
Topics: Humans; Pyoderma Gangrenosum; Sulfasalazine; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 38462891
DOI: 10.1177/12034754241238713 -
BMC Musculoskeletal Disorders Mar 2024Chronic low back pain (CLBP) is a prevalent and debilitating condition, leading to significant challenges to both patients and the governmental healthcare system....
BACKGROUND
Chronic low back pain (CLBP) is a prevalent and debilitating condition, leading to significant challenges to both patients and the governmental healthcare system. Non-pharmacologic interventions have received increasing attention as potential strategies to alleviate chronic low back pain and improve patient outcomes. The aim of this systematic review was to comprehensively assess the changes in blood inflammatory biomarkers after non-pharmacologic interventions for CLBP patients, thus trying to understand the complex interactions between non-pharmacologic interventions and inflammatory biomarker changes in CLBP.
METHODS
A thorough search (from January 1st, 2002 to October 5th, 2022) of PubMed, Medline (platform Web of Science), and the Cochrane Library (platform Wiley Online Library) were conducted, and inclusion criteria as well as exclusion criteria were refined to selection of the studies. Rigorous assessments of study quality were performed using RoB 2 from Cochrane or an adaptation of the Downs and Black checklist. Data synthesis includes alterations in inflammatory biomarkers after various non-pharmacologic interventions, including exercise, acupressure, neuro-emotional technique, and other modalities.
RESULTS
Thirteen primary studies were included in this systematic review, eight randomized controlled trials, one quasi-randomized trial, and four before-after studies. The interventions studied consisted of osteopathic manual treatment (one study), spinal manipulative therapy (SMT) (three studies), exercise (two studies), yoga (two studies) and acupressure (two studies), neuro-emotional technique (one study), mindfulness-based (one study) and balneotherapy study (one study). Four studies reported some changes in the inflammatory biomarkers compared to the control group. Decreased tumor necrosis factor-alpha (TNF-α) after osteopathic manual treatment (OMT), neuro-emotional technique (NET), and yoga. Decreased interleukin (IL)-1, IL-6, IL-10, and c-reactive protein (CRP) after NET, and increased IL-4 after acupressure. Another five studies found changes in inflammatory biomarkers through pre- and post-intervention comparisons, indicating improvement outcomes after intervention. Increased IL-10 after balneotherapy; decreased TNF-α, IL-1β, IL-8, Interferon-gamma, interferon-γ-induced protein 10-γ-induced protein 10 after exercise; decreased IL-6 after exercise and SMT; decreased CRP and chemokine ligand 3 after SMT.
CONCLUSION
Results suggest a moderation of inflammatory biomarkers due to different non-pharmacologic interventions for CLBP, generally resulting in decreased pro-inflammatory markers such as TNF-α and IL-6 as well as increased anti-inflammatory markers such as IL-4, thus revealing the inhibition of inflammatory processes by different non-pharmacologic interventions. However, a limited number of high-quality studies evaluating similar interventions and similar biomarkers limits the conclusion of this review.
Topics: Humans; Low Back Pain; Interleukin-10; Tumor Necrosis Factor-alpha; Interleukin-6; Interferon-gamma; Interleukin-4; Biomarkers; Chronic Pain; Randomized Controlled Trials as Topic
PubMed: 38459458
DOI: 10.1186/s12891-024-07289-1 -
Skin Research and Technology : Official... Mar 2024The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine,... (Review)
Review
AIMS AND OBJECTIVES
The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions.
METHOD
Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles.
RESULTS
In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%).
CONCLUSION
Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness.
Topics: Humans; Methotrexate; Azathioprine; Vitiligo; Mycophenolic Acid; Minocycline; Alefacept; Cyclosporine; Adrenal Cortex Hormones; Hypopigmentation; Simvastatin; Zinc; Purines; Pyrazoles; Sulfonamides; Azetidines; Thalidomide
PubMed: 38454597
DOI: 10.1111/srt.13642