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The Cardiovascular Risks of Fostamatinib in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

ABSTRACT: Objective: This systematic review and meta-analysis is aimed at assessing the risks of cardiovascular adverse events in patients with rheumatoid arthritis (RA) who have been treated with fostamatinib. Methods: The electronic databases of OVID Medline, OVID EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science were searched to identify studies that reported cardiovascular events or hypertension in RA patients treated with fostamatinib. Two reviewers separately and simultaneously screened the retrieved studies based on study selection criteria, collected data and performed methodological quality assessments. The effect size of meta-analysis was estimated by the Peto odds ratio (OR) or relative risk (RR) with 95% confidence intervals (95%CI). Funnel plot was used to estimate publication bias and sensitivity analysis was performed to test the robustness of the results. Results: A total of 12 trials composed of 5,618 participants with low to moderate risk of bias were included. In comparison to the placebo, the use of fostamatinib was found to elevate the risk of hypertension (RR=3.82, 95%CI 2.88-5.05) but was not associated with the risks of all-cause death (Peto OR=0.16, 95%CI 0.02-1.24), major adverse cardiovascular events (Peto OR=1.24, 95%CI 0.26-5.97), pulmonary heart disease and disease of pulmonary circulation (Peto OR=1.23, 95%CI 0.13-11.87), in addition to other forms of heart disease (Peto OR=1.96, 95%CI 0.72-5.38). Furthermore, sensitivity analysis showed no significant change in effective trends and no publication bias was found. Conclusion: Fostamatinib is associated with increased risk of hypertension; however, no increased risks of cardiovascular events were observed. Further well-planned cohort studies with large study populations and longer follow-up times are needed to elucidate the outcomes. Systematic Review Registration: [PROSPERO], identifier [CRD42020198217].

SUBMITTER: Chen Y

PROVIDER: S-EPMC8327174 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Objective: This study aimed to assess neoplasm risk in patients with rheumatoid arthritis (RA) treated with fostamatinib. Methods: Studies were collected from electronic databases of OVID Medline, OVID EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. We included studies that reported neoplasms in patients with RA treated with fostamatinib. Study selection was repeated by two reviewers based on the study selection criteria. Data were collected and methodological quality assessment was performed. Data were pooled using the Peto odds ratio (OR) with a 95% confidence interval (CI). Subgroup analyses of the fostamatinib dose, trial duration, neoplasm nature, and neoplasm-originating systems were conducted. A funnel plot was used to estimate publication bias, and sensitivity analysis was performed to test the robustness of the results. Results: Seven trials involving 4,971 participants showing low to moderate risk of bias were included. Compared with the placebo, fostamatinib use was not associated with the risks of overall neoplasms (Peto OR = 2.62, 95%CI 0.97-7.10), malignant neoplasms (Peto OR = 3.08, 95%CI 0.96-9.91), or benign neoplasms (Peto OR = 1.71, 95%CI 0.26-11.36). Nevertheless, compared with the placebo, a longer duration of fostamatinib use had a higher risk of malignant neoplasms (Peto OR = 4.49, 95%CI 1.03-19.60) at 52 weeks. As for malignant neoplasms in the digestive system, lower doses of fostamatinib reduced the neoplasm risk (100 mg bid vs 150 mg qd: Peto OR = 0.06, 95%CI 0.01-0.59). Sensitivity analysis showed no significant differences in the effective trends, and no publication bias was found. Conclusion: Fostamatinib is not associated with the risks of overall neoplasms as compared to placebo. Nevertheless, a longer duration of fostamatinib use may be associated with a risk of malignant neoplasms and higher doses of fostamatinib may increase malignant neoplasms in the digestive system. Further well-planned cohort studies with a larger study population are needed to elucidate these outcomes. Systematic Review Registration: PROSPERO (CRD42020202121).

Project description:Background: Rheumatoid arthritis is a type of systemic and complex autoimmune other disease characterized by chronic joint inflammation. Spleen tyrosine kinase (Syk) inhibitors are regarded as an effective alternative to existing drugs for the treatment of this disease. However, studies evaluating fostamatinib, a new Syk inhibitor, are either invalid or insufficient. Through a systematic review and meta-analysis, we evaluated the efficacy and safety of fostamatinib at different dosages in rheumatoid arthritis patients that display an inadequate response to methotrexate or disease-modifying antirheumatic drugs. Methods: Randomized controlled trials published between January 2000 and November 2018 were retrieved from PubMed, Embase, Medline, Web of Science, and The Cochrane Library. We also searched a relevant website (www.clinicaltrials.gov) for retrieval of unpublished data. These studies compared different dosages of fostamatinib to placebo, including the intake of 100 mg fostamatinib twice per day (bid) for 4 weeks followed by 150 mg once per day (qd) vs. the intake of 100 mg bid. Results: Two investigators analyzed 11 randomized placebo-controlled trials consisting of 3,680 patients. Compared to placebo, fostamatinib resulted in an obvious reduction in the American College of Rheumatology 20% response standard [weighted mean difference (WMD) 1.96, 95% confidence interval (CI) [1.46, 2.61], P < 0.001] and disease activity score < 2.6 (WMD 4.70, 95% CI [3.14, 7.03], P < 0.001). Regarding safety, the incidence of serious adverse reactions was higher in the fostamatinib group than in the placebo group [risk ratio (RR) 2.10, 95% CI [1.57, 2.80], P < 0.001]. The same was true for other adverse events [RR 1.63, 95%CI [1.33, 2.01], P < 0.001]. Conclusions: Fostamatinib is an effective and safe therapeutic medicine administered to patients with rheumatoid arthritis over 24 weeks. It can alleviate the degree of swelling and inflammation of the joints. Furthermore, 100 mg bid can be considered the most beneficial regimen over a 24-week period. More data are however needed to clarify the incidence of other adverse events and serious adverse reactions.

Project description:Background: Janus kinase (JAK) inhibitors have emerged as a progressively utilized therapeutic approach for the management of rheumatoid arthritis (RA). However, the complete determination of their cardiovascular safety remains inconclusive. Hence, the primary objective of this network meta-analysis is to meticulously assess and juxtapose the cardiovascular risks linked to distinct JAK inhibitors employed in RA patients. Methods: A systematic review and network meta-analysis were meticulously conducted, encompassing a collection of randomized controlled trials (RCTs) that focused on investigating the incidence of major adverse cardiovascular events (MACE) and all-cause mortality associated with Janus kinase (JAK) inhibitors administered to patients with rheumatoid arthritis (RA). Extensive exploration was performed across multiple electronic databases, incorporating studies published until March 2023. To be included in this analysis, the RCTs were required to involve adult participants diagnosed with RA who received treatment with JAK inhibitors. To ensure accuracy, two authors independently undertook the selection of eligible RCTs and meticulously extracted aggregate data. In order to examine the outcomes of MACE and all-cause mortality, a frequentist graph theoretical approach within network meta-analyses was employed, utilizing random-effects models. Third study has been registered on PROSPERO under the reference CRD42022384611. Findings: A specific selection encompassing a total of 14 meticulously chosen randomized controlled trials was undertaken, wherein 13,524 patients were assigned randomly to distinct treatment interventions. The analysis revealed no notable disparity in the occurrence of major adverse cardiovascular events (MACE) between the interventions and the placebo group. However, in comparison to adalimumab, the employment of JAK inhibitors exhibited an association with higher rates of all-cause mortality [odds ratio (OR): 1.7, 95% confidence interval (CI): 1.02-2.81]. This observed increase in risk primarily stemmed from the usage of tofacitinib (OR: 1.9, 95% CI: 1.12-3.23). None of the other JAK inhibitors exhibited a statistically significant variance in all-cause mortality when compared to adalimumab. Interpretation: Our study suggests that JAK inhibitors may not increase the risk of MACE in RA patients but may be associated with a higher risk of all-cause mortality compared to adalimumab, primarily due to tofacitinib use. Rheumatologists should carefully consider the cardiovascular risks when prescribing JAK inhibitors, particularly tofacitinib, for RA patients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=384611, CRD42022384611.

Project description:BackgroundPatients with rheumatoid arthritis (RA) have difficulties maintaining employment due to the impact of the disease on their work ability. This review aims to investigate the employment rates at different stages of disease and to identify predictors of employment among individuals with RA.MethodsThe study was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines focusing on studies reporting employment rate in adults with diagnosed RA. The literature review included cross-sectional and cohort studies published in the English language between January 1966 and January 2023 in the PubMed, Embase and Cochrane Library databases. Data encompassing employment rates, study demographics (age, gender, educational level), disease-related parameters (disease activity, disease duration, treatment), occupational factors, and comorbidities were extracted. Quality assessment was performed employing Newcastle-Ottawa Scale. Meta-analysis was conducted to ascertain predictors for employment with odds ratios and confidence intervals, and test for heterogeneity, using chi-square and I2-statistics were calculated. This review was registered with PROSPERO (CRD42020189057).ResultsNinety-one studies, comprising of a total of 101,831 participants, were included in the analyses. The mean age of participants was 51 years and 75.9% were women. Disease duration varied between less than one year to more than 18 years on average. Employment rates were 78.8% (weighted mean, range 45.4-100) at disease onset; 47.0% (range 18.5-100) at study entry, and 40.0% (range 4-88.2) at follow-up. Employment rates showed limited variations across continents and over time. Predictors for sustained employment included younger age, male gender, higher education, low disease activity, shorter disease duration, absence of medical treatment, and the absence of comorbidities. Notably, only some of the studies in this review met the requirements for high quality studies. Both older and newer studies had methodological deficiencies in the study design, analysis, and results reporting.ConclusionsThe findings in this review highlight the prevalence of low employment rates among patients with RA, which increases with prolonged disease duration and higher disease activity. A comprehensive approach combining clinical and social interventions is imperative, particularly in early stages of the disease, to facilitate sustained employment among this patient cohort.

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The Cardiovascular Risks of Fostamatinib in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

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