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BackgroundThe ORAL Surveillance trial showed a potentially higher incidence of malignancy and major adverse cardiovascular events (MACEs) associated with tofacitinib than those associated with tumor necrosis factor (TNF) inhibitors (TNFis). However, few studies have compared the safety of non-TNFis or other Janus kinase (JAK) inhibitors (JAKis). This study was aimed at comparing the incidence rates (IRs) of malignancies and MACEs in patients with rheumatoid arthritis (RA) treated using interleukin-6 (IL-6) inhibitors (IL-6is) or JAKis.MethodsWe retrospectively analyzed 427 patients with RA who were treated using an IL-6i (n = 273) or a JAKi (n = 154). We determined the IRs of malignancy and MACEs, and the standardized incidence ratio (SIR) of malignancies and investigated factors related to malignancy and MACEs. After adjusting the clinical characteristic imbalance by propensity score matching (PSM), we compared the IRs of adverse events between the JAKi and IL-6i groups.ResultsAfter PSM, the observational period was determined to be 605.27 patient-years (PY), and the median observational period was determined to be 2.28 years. We identified seven cases of malignancy (IR: 2.94 per 100 PY) in the JAKi-treated group and five cases (IR: 1.36 per 100 PY) in the IL-6i-treated group after PSM. The IR of MACEs was 2.56 and 0.83 (per 100 PY) in the JAKi- and IL-6i-treated groups. The IRRs of JAKi-treated patients versus IL-6i-treated patients were 2.13 (95% confidence interval (CI): 0.67–7.42) for malignancy and 3.03 (95% CI: 0.77–15.21) for MACE. There were no significant differences in IRR for malignancy and MACE between both groups after PSM. Univariate and multivariable Cox regression analyses revealed that older age and JAKi use were independent risk factors for malignancy, while older age, hypertension, and JAKi use were independent risk factors for MACEs. The overall malignancy SIR was significantly higher in the JAKi-treated group compared to the general population (2.10/100 PY, 95% CI: 1.23–2.97).ConclusionThe IRs of malignancy and MACE in patients with RA after PSM were comparable between IL-6i-treated and JAKi-treated patients. However, the SIR of malignancy in JAKi treatment was significantly higher than in the general population; therefore, further safety studies comparing JAKi to non-TNFi biologic disease-modifying antirheumatic drugs (bDMARDs) are needed.

Temporal arteritis (TA) is a large-vessel vasculitis mostly seen in older patients. Amyloid A (AA) amyloidosis secondary to a chronic inflammation induces multiple organ dysfunctions, including a dysfunction of the gastrointestinal tract. Herein, we present a case of TA complicated by AA amyloidosis that was resistant to oral and intravenous steroids. An 80-year-old man with a history of new-onset headache, jaw claudication, and distended temporal arteries was referred to our department. On admission, the patient presented with tenderness and a subcutaneous temporal nodule in both temple arteries. Ultrasonography of the nodule revealed an anechoic perivascular halo surrounding the right temporal artery. Following the diagnosis of TA, high-dose prednisolone therapy was initiated. However, the patient presented with recurrent abdominal pain and refractory diarrhea. Due to the unclear origin of refractory diarrhea, an extensive workup, including biopsy of the duodenal mucosa, was performed. Endoscopy revealed chronic inflammation in the duodenum. Immunohistochemical analysis of duodenal mucosal biopsy samples revealed AA amyloid deposition resulting in the diagnosis of AA amyloidosis. After tocilizumab (TCZ) administration, refractory diarrhea reduced; however, the patient died of intestinal perforation 1 month after the start of TCZ administration. Gastrointestinal involvement was the main clinical manifestation of AA amyloidosis in the present case. This case highlights the importance of bowel biopsy screening for amyloid deposition in patients with unexplained gastrointestinal tract symptoms, even in a recent onset of large-vessel vasculitis. In the present case, the carriage of the SAA1.3 allele likely contributed to the rare association of AA amyloidosis with TA.

Altered expression of adhesion molecules in immune cells has been demonstrated in rheumatoid arthritis (RA). Carcinoembryonic–antigen–related cell–adhesion molecule 1 (CEACAM1) is an adhesion molecule that acts as a coinhibitory receptor in the immune system. We investigated the role of CEACAM1 in immune cell subsets of patients with RA. Peripheral blood was obtained from 37 patients with RA and 20 healthy controls (HC). The expression of CEACAM1 and T–cell immunoglobulin mucin domain molecule (TIM) –3 on peripheral blood mononuclear cells and neutrophils was analyzed by flow cytometry. Intracellular TIM–3 expression was analyzed using cellular lysates by Western blot analysis. Serum levels of soluble CEACAM1 (sCEACAM1) were estimated by an enzyme-linked immunosorbent assay. CEACAM1 expression was not detected in peripheral blood mononuclear cells, including in CD14(+) monocytes and CD3(+) lymphocytes isolated from patients with RA or HC. However, substantial cell–surface expression of CEACAM1 was detected in peripheral blood neutrophils, and it was significantly elevated in samples from patients with RA without remission compared to those in remission. There was no significant difference in serum levels of sCEACAM1 between patients with RA and HC. Cell-surface expression of TIM-3 was not detected in peripheral blood neutrophils from patients with RA or HC but was seen in CD14(+) monocytes. However, there was no significant difference in TIM–3 expression on monocytes between patients with RA and HC. Our data indicate that cell-surface expression of CEACAM1 on peripheral blood neutrophils are higher in patients with RA and that it is associated with rheumatoid inflammation. Further studies are needed to explore the potential role of CEACAM1 in rheumatoid inflammatory pathways.