Adverse cardiovascular events in rheumatoid arthritis patients treated with JAK inhibitors: An analysis of postmarketing spontaneous safety reports.

OBJECTIVES: The ORAL Surveillance trial, a postmarketing safety clinical trial, found an increased risk of adverse cardiovascular events and venous thromboembolism (VTE) in patients treated with Janus Kinase (JAK) inhibitors compared to tumor necrosis factor (TNF) inhibitors. However, additional studies yielded mixed results and data on other JAK inhibitors are limited. METHODS: A retrospective, pharmacovigilance study using the FDA adverse event reporting system (FAERS) to assess reporting of adverse cardiovascular events following treatment with JAK inhibitors in rheumatoid arthritis (RA) patients between January 2015 and June 2023. To identify disproportionately increased reporting, an adjusted reporting odds ratio (adj.ROR) was calculated with a multivariable logistic regression model. RESULTS: We identified safety reports of 75,407 RA patients treated with JAK inhibitors (tofacitinib, n = 52,181; upadacitinib, n = 21,006; baricitinib, n = 2,220) and 303,278 patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs; TNF inhibitors, rituximab, and tocilizumab). The mean age was 61.2(±12) and 59.0(±13), respectively; 82 % and 81 % were women. Compared to bDMARDs, JAK inhibitors were associated with an increased reporting of VTE [n = 1,393, adj.ROR=2.11 (1.97-2.25)], stroke [n = 973, adj.ROR=1.25 (1.16-1.34)], ischemic heart disease [IHD, n = 999, adj.ROR=1.23 (1.13-1.33)], peripheral edema [n = 2699, adj.ROR=1.22 (1.17-1.28)], and tachyarrhythmias [n = 370, adj.ROR=1.15 (1.00-1.33)]. Most of the events occurred in the first year after treatment initiation. When different JAK inhibitors were compared, VTE, stroke, and IHD were more frequently reported with upadacitinib and baricitinib than tofacitinib. When stratified by age category, all safety signals were statistically significant in patients aged≤65 years. CONCLUSION: In this global postmarketing study, JAK inhibitors are associated with increased reporting of VTE, stroke, IHD, and tachyarrhythmias. These adverse events were reported following all JAK inhibitors that were studied, suggesting a class effect.

Endometriosis and autoimmunity: Can autoantibodies be used as a non-invasive early diagnostic tool?

This review aims to assess the current and past literature for efficacious non-invasive diagnostic markers for earlier detection of endometriosis. We briefly discussed the associations of endometriosis with other autoimmune diseases (AID), as well as the broad changes that occur within the immune system. Specifically, we focused on the usage of various autoantibodies as a potential non-invasive diagnostic tool. Autoantibodies have been noted in the literature since the 1980s and their usage could possibly reduce the delay of an endometriosis diagnosis. Our search concluded that various anti endometrial antibodies may offer useful diagnostic tools. Anti-SLP2, anti-TMOD3, anti-TPM3, and anti-PDIK1L are particularly useful for early diagnosis in minimal to mild endometriosis. Anti-alpha enolase could also be used but yields results similar to CA125. Other non anti endometrial antibodies like anti-IMP1, anti-CA, aCL, anti-STX5 may be used as additional non-invasive diagnostic tools. Anti-TPO may be beneficial in patients in endometriosis patients with concurrent polycystic ovaries syndrome (PCOS). As the pathogenesis of endometriosis continues to reveal itself, more autoantibodies are being discovered and they may offer useful non-invasive tools for the early diagnosis of endometriosis.