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• Current evidence suggests similar risk of rheumatoid arthritis (RA) statin users vs non-users. • Risk of RA may be decreased with higher statin treatment persistence or intensity. • Studies evaluating cumulative statin exposure on the risk of RA are warranted. Anti-inflammatory and immune-modulating effects of statins suggest that they may play a role in the risk of rheumatoid arthritis (RA). We aimed to perform a systematic review and meta-analysis of studies assessing the risk of RA in statin-users versus non-users. We searched Medline from inception to 01/22/2019 and Embase from 1988 to Week 03 2019 for studies that examined the association between statin use and RA without restrictions on language. We identified 1,161 references; of them 8 studies (5 cohort studies and 3 case-control studies) were included in the systematic review. Four cohort studies comparing statin-users versus non-users were included in the meta-analysis. The pooled risk ratio (RR) was 1.01; 95%CI 0.93–1.10; I 2 = 17%. Case-control studies showed highly heterogeneous results (I 2 = 92%) and were not included in the meta-analysis. One cohort study and one case-control study assessing persistence with or intensity of treatment with statins showed lower risk of RA with higher versus lower treatment persistence or intensity of statin use (pooled RR 0.66; 95%CI 0.5–0.87; I 2 = 83%). The certainty in the evidence was low. In this systematic review and meta-analysis, we observed no difference in risk of RA in statin users vs non-users. Risk of RA may be lower in patients with higher versus lower statin treatment persistence or intensity. Future observational studies with guards against selection bias and confounding are needed to further elucidate the impact of statin use on the risk of RA, considering potential differences by dosage, duration of use, study population and other factors. [ABSTRACT FROM AUTHOR]

Previously, we demonstrated in test and validation cohorts that type I IFN (T1IFN) activity can predict non-response to tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA). In this study, we examine the biology of non-classical and classical monocytes from RA patients defined by their pre-biologic treatment T1IFN activity. We compared single cell gene expression in purified classical (CL, n = 342) and non-classical (NC, n = 359) monocytes. In our previous work, RA patients who had either high IFNβ/α activity (>1.3) or undetectable T1IFN were likely to have EULAR non-response to TNFi. In this study comparisons were made among patients grouped according to their pre-biologic treatment T1IFN activity as clinically relevant: "T1IFN undetectable (T1IFN ND) or IFNβ/α >1.3" (n = 9) and "T1IFN detectable but IFNβ/α ≤ 1.3" (n = 6). In addition, comparisons were made among patients grouped according to their T1IFN activity itself: "T1IFN ND," "T1IFN detected and IFNβ/α ≤ 1.3," and "IFNβ/α >1.3." Major differences in gene expression were apparent in principal component and unsupervised cluster analyses. CL monocytes from the T1IFN ND or IFNβ/α >1.3 group were unlikely to express JAK1 and IFI27 (p < 0.0001 and p 0.0005, respectively). In NC monocytes from the same group, expression of IFNAR1, IRF1, TNFA, TLR4 (p ≤ 0.0001 for each) and others was enriched. Interestingly, JAK1 expression was absent in CL and NC monocytes from nine patients. This pattern most strongly associated with the IFNβ/α>1.3 group. Differences in gene expression in monocytes among the groups suggest differential IFN pathway activation in RA patients who are either likely to respond or to have no response to TNFi. Additional transcripts enriched in NC cells of those in the T1IFN ND and IFNβ/α >1.3 groups included MYD88, CD86, IRF1, and IL8. This work could suggest key pathways active in biologically defined groups of patients, and potential therapeutic strategies for those patients unlikely to respond to TNFi. [ABSTRACT FROM AUTHOR]

To compare the frequency of and trends in hospitalizations after heart failure (HF) diagnosis in patients with and without rheumatoid arthritis (RA) during 1987–2015. The study included a retrospectively identified population-based cohort of patients with incident HF and prior RA (age≥18 years, 1987 ACR criteria) and a cohort of incident HF patients without RA matched 3:1 on age, sex, and year of HF diagnosis. Hospitalizations at the time of HF diagnosis were excluded. All subjects were followed until death, migration, or 12/31/2015. The study included 212 patients with RA (mean age at HF diagnosis 78.3 years; 68% female) and 636 non-RA patients (mean age at HF diagnosis 78.6 years; 68% female). The hospitalization rate after HF diagnosis was higher in RA vs non-RA (rate ratio [RR] 1.17; 95%CI 1.08-1.26). Hospitalization rates in both groups have been declining since 2005 and the difference between patients with and without RA may be decreasing after 2010. The magnitude of the increase was similar in both sexes and across all ages. Patients with RA were more likely to be hospitalized for non-cardiovascular causes (RR 1.26; 95%CI 1.14-1.39), but not for HF or other cardiovascular causes compared to non-RA patients. The hospitalization rate following HF diagnosis was higher in RA versus non-RA patients regardless of sex and age. Increased hospitalization risk in patients with RA was driven by increased rates of non-cardiovascular hospitalization. [ABSTRACT FROM AUTHOR]

• Our study showed that approximately 49 % of ankylosing spondylitis (AS) patients had multimorbidity and identified five distinct multimorbidity phenotypes, highlighting the importance of the type of morbidity in addition to the number of morbidities for longitudinal outcomes in AS. • The depression cluster was associated with worse disease activity and function, thus emphasizing the importance of outlining optimal screening and management strategies for depression in AS. • Identifying AS multimorbidity clusters or phenotypes in clinical practice could help delineate individuals at the greatest risk of worse outcomes earlier and enable more comprehensive and effective care. To examine the association of multimorbidity phenotypes at baseline with disease activity and functional status over time in ankylosing spondylitis (AS). Patient-reported AS morbidities (comorbidities, N = 28 and extra-musculoskeletal manifestations, EMMs, N = 3) within 3 years of enrollment with a prevalence ≥1 %, were included from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) cohort. We defined multimorbidity as ≥2 morbidities (MM2+) and substantial multimorbidity as ≥5 morbidities (MM5+). Multimorbidity clusters or phenotypes were identified using K-median clustering. Disease activity (ASDAS-CRP) and functional status (BASFI) measures were collected every 6 months. Generalized estimating equation method was used to examine the associations of multimorbidity counts and multimorbidity clusters with measures of disease activity and functional status over time. Among 1,270 AS patients (9,885 visits) with a median follow-up of 2.9 years (IQ range: 1.0–6.8 years), the prevalence of MM2+ and MM5+ was 49 % and 9 % respectively. We identified five multimorbidity clusters: depression (n = 321, 25 %), hypertension (n = 284, 22 %), uveitis (n = 274, 22 %), no morbidities (n = 238, 19 %), and miscellaneous (n = 153, 12 %). Patients in the depression cluster were more likely to be female and had significantly more morbidities and worse disease activity and functional status compared to those with no morbidities. Approximately 49 % of AS patients in the PSOAS cohort had multimorbidity and five distinct multimorbidity phenotypes were identified. In addition to the number of morbidities, the type of morbidity appears to be important to longitudinal outcomes in AS. The depression cluster was associated with worse disease activity and function. [ABSTRACT FROM AUTHOR]

To examine time trends in glucocorticoid (GC) use among patients diagnosed with rheumatoid arthritis (RA) during the biologic era. A population-based inception cohort of RA patients diagnosed during 1999 – 2018 was followed longitudinally through their medical records until death, migration or 12/31/2020. All patients fulfilled 1987 American College of Rheumatology classification criteria for RA. GC start and stop dates were collected along with dosages in prednisone equivalents. The cumulative incidence of GC initiation and discontinuation adjusted for the competing risk of death was estimated. Cox models adjusted for age and sex were used to compare trends between time periods. The study population included 399 patients (71% female) diagnosed in 1999 – 2008 and 430 patients (67% female) diagnosed in 2009 – 2018. GC use was initiated within 6 months of meeting RA criteria in 67% of patients in 1999-2008 and 71% of patients in 2009-2018, corresponding to a 29% increase in hazard for initiation of GC in 2009-2018 (adjusted hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.09-1.53). Among GC users, similar rates of GC discontinuation within 6 months after GC initiation were observed in patients with RA incidence in 1999 – 2008 and 2009 – 2018 (39.1% versus 42.9%, respectively), with no significant association in adjusted Cox models (HR: 1.11; 95% CI: 0.93-1.31). More patients are initiating GCs early in their disease course now compared to previously. The rates of GC discontinuation were similar, despite the availability of biologics. [ABSTRACT FROM AUTHOR]

Objectives To assess the accuracy of dual-energy CT (DECT) for diagnosing gout, and to explore whether it can have any impact on clinical decision making beyond the established diagnostic approach using polarising microscopy of synovial fluid (diagnostic yield). Methods Diagnostic single-centre study of 40 patients with active gout, and 41 individuals with other types of joint disease. Sensitivity and specificity of DECT for diagnosing gout was calculated against a combined reference standard ( polarising and electron microscopy of synovial fluid). To explore the diagnostic yield of DECT scanning, a third cohort was assembled consisting of patients with inflammatory arthritis and risk factors for gout who had negative synovial fluid polarising microscopy results. Among these patients, the proportion of subjects with DECT findings indicating a diagnosis of gout was assessed. Results The sensitivity and specificity of DECT for diagnosing gout was 0.90 (95% CI 0.76 to 0.97) and 0.83 (95% CI 0.68 to 0.93), respectively. All false negative patients were observed among patients with acute, recent-onset gout. All false positive patients had advanced knee osteoarthritis. DECT in the diagnostic yield cohort revealed evidence of uric acid deposition in 14 out of 30 patients (46.7%). Conclusions DECT provides good diagnostic accuracy for detection of monosodium urate (MSU) deposits in patients with gout. However, sensitivity is lower in patients with recent-onset disease. DECT has a significant impact on clinical decision making when gout is suspected, but polarising microscopy of synovial fluid fails to demonstrate the presence of MSU crystals. [ABSTRACT FROM AUTHOR]

The authors focus on the potential use of cytokine biochemical markers in personalized therapy for rheumatoid arthritis (RA). It describes cytokines as a family of small proteins which tend to communicate signals among various cell types as part of the orchestration of immune-mediated processes. Several publications over the role of cytokine biochemical markers in RA are examined, one of which concerns the use of rolling cycle amplification over candidate plasma immune proteins.

To assess transition probability between different levels of functional disability (FD) and time spent with FD in patients with versus without rheumatoid arthritis (RA) after RA incidence/index date. This retrospective population-based cohort study included Olmsted County, Minnesota residents (1987 ACR criteria met in 1999–2013) and comparators without RA from the same area with similar age, sex and RA incidence/index date. Activities of Daily Living (ADL) were obtained by self-report questionnaires annually since 1999. FD was defined as having difficulty with ≥1 ADL. Multistate modeling was used to estimate the probability of transitioning between FD states. Five hundred fifty-eight patients with RA and 457 comparators completed ≥2 questionnaires and were included. Patients with RA had increased risk of transitioning from no FD to FD: Hazard Ratio (HR) 2.4; 95%CI:1.9–3.0. Each additional FD at RA onset reduced the probability of returning to no FD by 14%. However, the probability of having ≥1 FD was stable between RA incidence and 10-year follow-up. In the first 15 years of disease, patients with RA spent on average 10.1 years without FD and 3.4 years with ≥1 FD versus 11.6 years and 2.0 years (p <0.001) in comparators. Patients with RA remain functionally disadvantaged compared to individuals without RA. The likelihood of returning to no FD in RA decreases with each additional preexisting FD. However, the probability of FD does not increase within 10 years of RA onset, potentially reflective of the benefits of disease-modifying treatments in RA. [ABSTRACT FROM AUTHOR]

The article compares the clinical presentation, management as well as outcome of heart failure in patients with rheumatoid arthritis (RA) with non-RA subjects. Methodology-wise, the researchers conducted a community-based cohort study. Based on the results, they concluded that the findings emphasize the importance of more vigilant screening in patients with RA for early signs of the disease.

The article discusses a study on the mortality trends among rheumatoid arthritis (RA) patients compared with those in the general population. The mortality rates for female and male RA patients were 2.4 and 2.5 per 100 person-years, respectively, between 1965 and 2005. It found that the difference between the observed and expected mortality rates increased in more recent years, which resulted in a wider mortality gap. The findings indicate that RA patients have not experienced improvements in survival over the period.

The article presents a study which examined the relationship between glucocorticoid exposure and cardiovascular (CV) events in patients with rheumatoid arthritis (RA). Results showed that rheumatoid factor (RF)-negative patients with exposure to glucocorticoids were not at increased risk of CV events. According to the authors, the findings suggest that glucocorticoids interact with RF status to modulate the occurrence of CV events in patients with RA.

To identify associations between immunostimulated cytokine production and disease characteristics, peripheral blood lymphocytes were collected from 155 adult patients with rheumatoid arthritis (RA) before and after a 5-year interval. The lymphocytes were activated in vitro with T-cell stimulants, cytosine-phosphate-guanine (CpG) oligonucleotide, and medium alone (negative control). Expression of 17 cytokines was evaluated with immunoassays, and factor analysis was used to reduce data complexity and identify cytokine combinations indicative of cell types preferentially activated by each immunostimulant. The findings showed that the highest numbers of correlations were between cytokine levels and rheumatoid factor (RF) positivity and between cytokine levels and disease duration. Scores for cytokines driven by CpG and medium alone were negatively associated with RF positivity and disease duration at baseline but positively associated with both at 5 years. Our findings suggest that RF expression sustained over time increases activation of B cells and monocytes without requirements for T-cell functions. • Cytokines were associated with rheumatoid factor and rheumatoid arthritis duration. • Cytokine profiles switched from T-cell to B-cell cytokines over 5 years. • Cytosine-phosphate-guanine response profiles suggested an innate immune response. • Sustained rheumatoid factor expression likely activates B cells and monocytes. [ABSTRACT FROM AUTHOR]

Background: Case reports and referral-based studies suggest spontaneous coronary artery dissection (SCAD) is associated with autoimmune diseases and causes 2% to 4% of acute coronary syndromes.Objectives: This study determined the association of SCAD with autoimmune diseases, together with incidence and recurrence, in a population-based study.Methods: This case-control study took place from 1995 to 2018 within the Rochester Epidemiology Project. The study identified cases with SCAD from diagnosis codes and verified them using coronary angiography images, matching each case to 3 control subjects on age, sex, county, and years of medical history. Autoimmune disease history came from a validated, code-based definition. A multivariable logistic regression model calculated the odds ratio (OR) for SCAD among patients with a history of autoimmune disease, adjusting for race and body mass index.Results: The study identified 114 cases with SCAD (mean age 51 years and 90% women) and 342 matched control subjects. Autoimmune disease occurred in 13 (11%) cases with SCAD and 40 (12%) control subjects (p = 0.93). Even after adjustment, autoimmune diseases were not associated with SCAD (OR: 0.81; 95% confidence interval [CI]: 0.40 to 1.66). SCAD incidence between 2010 and 2018 (2.7 per 100,000; 95% CI: 1.7 to 3.7) was 10-fold higher than the incidence between 1995 and 2009 (0.3 per 100,000; 95% CI: 0.0 to 0.6). SCAD recurrence was 10% (95% CI: 3% to 16%) at 5 years.Conclusions: These findings suggested SCAD pathogenesis is noninflammatory and screening for autoimmune diseases based on SCAD alone is not warranted. The code-based incidence of SCAD has increased over time, highlighting the importance of considering SCAD among patients with acute coronary syndromes. [ABSTRACT FROM AUTHOR]