Systemic inflammation response index is associated with increased all-cause and cardiovascular mortality in US adults with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) stands as a persistent systemic inflammatory autoimmune condition. Despite this understanding, the precise impact of the systemic inflammation response index (SIRI) on the prognosis of RA patients remains elusive. This study aims to elucidate the correlation between the inflammatory biomarker SIRI and both all-cause mortality and cardiovascular mortality among RA patients. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2020, a retrospective analysis was conducted. Survival data were depicted through Kaplan-Meier survival curves, while the relationship between SIRI and all-cause or cardiovascular mortality in RA patients was scrutinized via multivariable Cox proportional hazards regression analysis and restricted cubic spline plots. Furthermore, subgroup analysis and mediation analysis were also performed. RESULTS: This study encompassed 2656 RA patients with a comprehensive 20-year follow-up, during which 935 all-cause deaths and 273 deaths attributed to cardiovascular disease were recorded. We observed a nonlinear positive correlation between SIRI with both all-cause and cardiovascular mortality in RA patients. Notably, at a SIRI level of 1.12, the hazard ratio reached 1, indicating a shift from low to high mortality risk. Furthermore, mediation analysis revealed that 12.6% of the association between RA and mortality risk was mediated through SIRI. Subgroup analysis indicated a more pronounced association between SIRI and mortality in female patients or those with a high BMI. CONCLUSION: This study underscores a non-linear positive correlation between the biomarker SIRI and both all-cause mortality and cardiovascular mortality in RA patients.

Association between Life's Essential 8 and all-cause or cardiovascular-specific mortality in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) have been found to have a higher cardiovascular disease (CVD) burden. We aimed to examine the associations between Life's Essential 8 (LE8), a metric of cardiovascular health (CVH) recently proposed by the American Heart Association, and all-cause and CVD mortality in RA patients. METHODS: This prospective cohort study analysed RA patients from the National Health and Nutrition Examination Survey 2005-2018 with linked mortality data through December 31, 2019. Total LE8 scores were calculated and divided into the high- (LE8 80-100), moderate- (LE8 50-79), and low-CVH (LE8 0-49) groups. Weighted multivariable Cox regression, logistic regression and restricted cubic spline models were applied to explore the association between LE8 and outcomes. RESULTS: A total of 1424 RA patients were enrolled with a weighted mean age of 57.87 years and female proportion of 58.94%. During a median follow-up of 82 months, 270 all-cause (85 CVD) deaths were recorded. Compared with the high-CVH group, participants in the moderate- and low-CVH groups had an 85.8% and 129.5% increased risk of all-cause mortality, respectively. After adjustment for potential confounders, each 1 point decrease in LE8 score was associated with a 2.6% increased risk of CVD mortality. Subgroup analyses showed significant interactions between LE8 score and non-Hispanic white population with risk of all-cause mortality. The results were robust for all-cause mortality, but not for CVD mortality in the sensitivity analysis. CONCLUSIONS: CVH measured by the LE8 score is a robust and independent predictor of all-cause mortality among U.S. RA patients.

Risk for cardiovascular disease development in rheumatoid arthritis.

BACKGROUND: Patients with rheumatoid arthritis have significant cardiovascular mortality and morbidity. OBJECTIVE: To investigate the effects of chronic inflammation in rheumatoid arthritis on cardiovascular morbidity association with cardiovascular risk factors risk factors. Mortality report is secondary just to show trends without sufficient statistical power as it is accidental endpoint. METHODS: A total of 201 individuals without previous cardiovascular disease, 124 with rheumatoid arthritis (investigation group) and 77 with osteoarthritis (control group), were included in the study and followed up for an average of 8 years to assess the development of fatal or non-fatal cardiovascular diseases. The incidence and prevalence of cardiovascular risk factors were also investigated. RESULTS: The total incidence of one or more fatal or nonfatal cardiovascular events was 43.9% in the investigation group and 37.5% in the control group. Of these patients, 31.7% and 30.9% survived cardiovascular events in the investigation and control groups, respectively. The most common cardiovascular disease among participants who completed the study and those who died during the study was chronic heart failure. The results of the subgroup analysis showed that strict inflammation control plays a central role in lowering cardiovascular risk. CONCLUSION: A multidisciplinary approach to these patients is of paramount importance, especially with the cooperation of immunologists and cardiologists for early detection, prevention, and management of cardiovascular risks and diseases.

Rheumatoid Arthritis-Related Lung Disease and Its Association With Mortality.

PURPOSE: The aim of this study was to determine the association of rheumatoid arthritis-related lung disease (RA-LD) and its subtypes with all-cause mortality. MATERIALS AND METHODS: For the present analyses, patients with RA who underwent computed tomography of the chest (chest-CT) were evaluated. RA-LD was defined in 4 subtypes as follows: interstitial lung disease (RA-ILD), airway disease (RA-AD), rheumatoid pulmonary nodules (RA-PN), and RA-related pleural disease (RA-PD). The date of RA-LD diagnosis was considered the date of the first chest-CT detecting the pathology. To assess the factors associated with mortality, multivariable logistic regression analyses were performed with variables selected based on their causal associations with the outcome. RESULTS: Of 576 RA patients, 253 (43.9%) had RA-LD (38.7% male; mean age at RA-LD diagnosis, 59.9 ± 9.8 years). The most common subtype was RA-AD, which was detected in 119 (47.0%) patients followed by 107 (42.3%) with RA-ILD, 70 (27.7%) with RA-PN, and 31 (12.3%) with RA-PD. Sixty-one (24.1%) patients had 2+ subtypes. After median follow-up of 10.2 years, 97 (16.8%) died. The existence of at least 1 subtype and 2+ subtypes increased the all-cause mortality, as indicated by odds ratios of 1.60 (95% confidence interval [CI], 1.03-2.48) and 2.39 (95% CI, 1.26-4.54), respectively. Among RA-LD patients, RA-ILD and RA-PD were associated with increased mortality (odds ratios were 2.20 [95% CI, 1.18-4.08] and 1.62 [95% CI, 0.70-3.75], respectively). CONCLUSIONS: In this study, RA-AD was the most common subtype, and the presence of RA-LD increased mortality. This effect was particularly pronounced in patients with RA-ILD and RA-PD or those presenting with 2+ subtypes.

Elevations in adipocytokines and mortality in rheumatoid arthritis.

OBJECTIVES: This study assessed whether circulating levels of adiponectin and leptin are associated with higher mortality in patients with RA. METHODS: Participants were adults from the Veterans Affairs RA Registry. Adipokines and inflammatory cytokines were measured as part of a multi-analyte panel on banked serum at enrolment. Dates and causes of death were derived from the Corporate Data Warehouse and the National Death Index. Covariates were derived from medical record, biorepository and registry databases. Multivariable Cox proportional hazard models evaluated associations between biomarkers and all-cause and cause-specific mortality. RESULTS: A total of 2583 participants were included. Higher adiponectin levels were associated with older age, male sex, white race, lower BMI, autoantibody seropositivity, radiographic damage, longer disease duration, prednisone use and osteoporosis. Higher adiponectin concentrations were also associated with higher levels of inflammatory cytokines but not higher disease activity at enrolment. Leptin was primarily associated with greater BMI and comorbidity. The highest quartile of adiponectin (vs lowest quartile) was associated with higher all-cause mortality [hazard ratio (HR): 1.46 (95% CI: 1.11, 1.93), P = 0.009] and higher cardiovascular mortality [HR: 1.85 (95% CI: 1.24, 2.75), P = 0.003], after accounting for covariates. Higher leptin levels were also associated with greater all-cause and cancer mortality. CONCLUSIONS: Elevations in adipokines are associated with age, BMI, comorbidity and severe disease features in RA and independently predict early death. Associations between adiponectin and inflammatory cytokines support the hypothesis that chronic subclinical inflammation promotes metabolic changes that drive elevations in adipokines and yield adverse health outcomes.

Long-term persistence of rituximab in patients with rheumatoid arthritis: an evaluation of the UCL cohort from 1998 to 2020.

OBJECTIVES: B cell depletion therapy based on rituximab in patients with RA was pioneered at University College London Hospitals/University College London in 1998. The objective of this study was to evaluate long-term persistence of rituximab and identify factors associated with discontinuation of treatment. METHODS: Retrospective review of medical records from all rituximab-treated RA patients followed up in a dedicated clinic (1998-2020). Data collected included gender, disease duration, previous DMARDs, autoantibody status, age and concomitant therapy at first cycle, length of follow-up, and number of cycles. Drug survival and factors associated with drug discontinuation were analysed using Kaplan-Meier survival curves, log-rank test and Cox regression analysis. RESULTS: A total of 404 patients were included. Median disease duration and age at time of first rituximab cycle were 10 and 57 years, respectively. Median total follow-up was 55 months and median number of cycles five. 93.1% of patients were seropositive. Overall, 31.2% of patients stopped rituximab, with the largest reason for discontinuing being primary inefficacy (42.1%). Comparison of Kaplan-Meier curves showed that rituximab drug survival was lower in seronegative patients and in patients who had previously failed at least one biologic DMARD (bDMARD). Cox regression analysis revealed that rituximab discontinuation was associated with a greater number of previous bDMARDs. CONCLUSION: Many patients with RA achieve good control of their disease with repeated cycles of rituximab treatment. The most common reasons for treatment discontinuation were either primary or secondary inefficacy. Patients who were seronegative and who had previously failed other bDMARDs were more at risk of drug discontinuation.

Safety of Janus Kinase Inhibitors in Patients With Inflammatory Bowel Diseases or Other Immune-mediated Diseases: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Inhibitors of Janus kinases (JAKs) are being developed for treatment of inflammatory bowel diseases and other immune-mediated diseases. Tofacitinib is effective in treatment of ulcerative colitis, but there are safety concerns. We performed a systematic review and meta-analysis to investigate the safety profile of tofacitinib, upadacitinib, filgotinib, and baricitinib in patients with rheumatoid arthritis, inflammatory bowel diseases, psoriasis, or ankylosing spondylitis. METHODS: We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 1, 1990, through July 1, 2019. We performed a manual review of conference databases from 2012 through 2018. The primary outcome was incidence rates of adverse events (AEs) and serious AEs. We also estimated incidence rates of serious infections, herpes zoster infection, non-melanoma skin cancer, other malignancies, major cardiovascular events, venous thromboembolism, and mortality. We performed a meta-analysis, which included controlled studies, to assess the relative risk of these events. RESULTS: We identified 973 studies; of these, 82 were included in the final analysis, comprising 66,159 patients with immune-mediated diseases who were exposed to a JAK inhibitor. Two-thirds of the included studies were randomized controlled trials. The incidence rate of AEs was 42.65 per 100 person-years and of serious AEs was 9.88 per 100 person-years. Incidence rates of serious infections, herpes zoster infection, malignancy, and major cardiovascular events were 2.81 per 100 person-years, 2.67 per 100 person-years, 0.89 per 100 person-years, and 0.48 per 100 person-years, respectively. Mortality was not increased in patients treated with JAK inhibitors compared with patients given placebo or active comparator (relative risk 0.72; 95% confidence interval 0.40-1.28). The meta-analysis showed a significant increase in risk of herpes zoster infection among patients who received JAK inhibitors (relative risk 1.57; 95% confidence interval 1.04-2.37). CONCLUSIONS: In a systematic review and meta-analysis, we found an increased risk of herpes zoster infection among patients with immune-mediated diseases treated with JAK inhibitors. All other AEs were not increased among patients treated with JAK inhibitors.

Mortality over 14 years in MTX-refractory patients randomized to a strategy of addition of infliximab or sulfasalazine and hydroxychloroquine.

OBJECTIVE: To compare mortality risk over up to 14 years of follow-up in methotrexate-refractory patients with early RA randomized to a strategy starting with addition of infliximab vs addition of SSZ and HCQ. METHODS: Data was from the two-arm, parallel, randomized, active-controlled, open-label Swefot trial in which patients with early RA (symptom duration <1 y) were recruited from 15 rheumatology clinics in Sweden (2002-2005). Patients who did not achieve low disease activity after 3-4 months of MTX were randomized to addition of infliximab (n = 128) or SSZ and HCQ (n = 130). Participants were followed until death, emigration, or end of follow-up, whichever came first. Analyses were by intention-to-treat. RESULTS: Over an average follow-up of 13 years, there were 13 and 16 deaths, respectively [8.8 vs 10.6 deaths per 1000 person-years; mortality hazard ratio 1.2 (95% CI: 0.6, 2.5); P =0.62]. The 1-year mortality was 0.8% in both treatment arms, the 5-year mortality was 2.3% for the infliximab arm compared with 1.5% for the conventional combination treatment arm, while the 10-year mortality was 7.8% and 7.7%, respectively. After 5 years, ∼50% of patients in the conventional combination therapy arm had switched to biologic treatment, and 50% in the biologic arm had discontinued treatment with a biologic DMARD. CONCLUSION: No difference in mortality risk could be observed over up to 14 years of follow-up between treatment strategy groups. At 5 years (3 years after trial cessation), 50% of patients remained on their assigned therapy, reflecting that DMARD combination is an adequate treatment strategy in 50% of patients. TRIAL REGISTRATION: clinicaltrials.gov, identifier: NCT00764725.

Rheumatoid arthritis related interstitial lung disease - improving outcomes over 25 years: a large multicentre UK study.

OBJECTIVE: This study explores whether the prognosis of interstitial lung disease in rheumatoid arthritis (RA-ILD) has improved over time and assesses the potential influence of drug therapy in a large multicentre UK network. METHODS: We analysed data from 18 UK centres on patients meeting criteria for both RA and ILD diagnosed over a 25-year period. Data included age, disease duration, outcome and cause of death. We compared all cause and respiratory mortality between RA controls and RA-ILD patients, assessing the influence of specific drugs on mortality in four quartiles based on year of diagnosis. RESULTS: A total of 290 RA-ILD patients were identified. All cause (respiratory) mortality was increased at 30% (18%) compared with controls 21% (7%) (P =0.02). Overall, prognosis improved over quartiles with median age at death rising from 63 years to 78 years (P =0.01). No effect on mortality was detected as a result of DMARD use in RA-ILD. Relative risk (RR) of death from any cause was increased among patients who had received anti-TNF therapy [2.09 (1.1-4.0)] P =0.03, while RR was lower in those treated with rituximab [0.52(0.1-2.1)] or mycophenolate [0.65 (0.2-2.0)]. Patients receiving rituximab as their first biologic had longer three (92%), five (82%) and seven year (80%) survival than those whose first biologic was an anti-TNF agent (82%, 76% and 64%, respectively) (P =0.037). DISCUSSION: This large retrospective multicentre study demonstrates survival of patients with RA-ILD has improved. This may relate to the increasing use of specific immunosuppressive and biologic agents.

Cardiovascular risk and mortality in rheumatoid arthritis compared with diabetes mellitus and the general population.

OBJECTIVES: To compare risk of cardiovascular disease and mortality in patients with incident RA, diabetes mellitus (DM) and the general population (GP). METHODS: Patients diagnosed with incident RA were matched 1:5 by age, sex and year of RA diagnosis with the GP. In the same period, patients with incident DM were included. Outcomes were heart failure (HF), myocardial infarction (MI), coronary revascularization, stroke, major adverse cardiovascular events (MACE) and death up to 10 years after diagnosis. RESULTS: We included 15 032 patients with incident RA, 301 246 patients with DM and 75 160 persons from the GP. RA patients had an increased risk of HF [hazard ratio (HR) 1.51, 95% CI: 1.38, 1.64], MI (HR 1.58, 95% CI: 1.43, 1.74), percutaneous coronary intervention (PCI; HR 1.44, 95% CI: 1.27, 1.62), coronary artery bypass grafting (CABG; HR 1.30, 95% CI: 1.05, 1.62) and stroke (HR 1.22, 95% CI: 1.12-1.33) compared with the GP. However, the 10-year all-cause mortality was at the same level as observed in the GP. Cardiac death and MACE were increased in RA compared with the GP. When compared with patients with DM, RA patients had a lower adjusted risk of HF (HR 0.79, 95% CI: 0.73, 0.85), CABG (HR 0.62, 95% CI: 0.51, 0.76) and stroke (HR 0.82, 95% CI: 0.76, 0.89), and similar risk of MI and PCI. DM patients had the highest risk of 10-year mortality, cardiac death and MACE. CONCLUSION: This study demonstrates that RA is associated with an increased risk of HF, MI, stroke and coronary revascularization than found in the GP but without reaching the risk levels observed in DM patients.

Outcomes of abdominal aortic aneurysm repair among patients with rheumatoid arthritis.

OBJECTIVE: In the present study, we compared the outcomes of elective abdominal aortic aneurysm (AAA) repair in patients with and without rheumatoid arthritis (RA) stratified by the type of surgery. METHODS: A retrospective population-based cohort study was conducted from 2003 to 2016. Linked administrative health data from Ontario, Canada were used to identify all patients aged ≥65 years who had undergone elective open or endovascular AAA repair during the study period. Patients were identified using validated procedure and billing codes and matching using propensity scores. The primary outcome was survival. The secondary outcomes were major adverse cardiovascular events (MACE)-free survival (defined as freedom from death, myocardial infarction, and stroke), reintervention, and secondary rupture. RESULTS: Of 14,816 patients undergoing elective AAA repair, a diagnosis of RA was present for 309 (2.0%). The propensity-matched cohort included 234 pairs of RA and control patients. The matched cohort was followed up for a mean ± standard deviation of 4.93 ± 3.35 years, and the median survival was 6.76 and 7.31 years for the RA and control groups, respectively. Cox regression analysis demonstrated no statistically significant differences in the hazards for death, MACE, reintervention, or secondary rupture. Analysis of the differences in outcomes stratified by repair approach also showed no statistically significant differences in the hazards for death, MACE, reintervention, or secondary rupture. CONCLUSIONS: We found no statistically significant differences in survival, MACE, reintervention, or secondary rupture among patients with RA undergoing elective AAA repair compared with controls. Further studies are required to evaluate the impact of comorbidities and antirheumatic medications on the outcomes of elective AAA repair.

Factors associated with mortality in rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis.

BACKGROUND: Interstitial lung disease (ILD) is a common and potentially life-threatening complication for rheumatoid arthritis (RA) patients. However, there is a lack of clear prognostic factors in rheumatoid arthritis-associated interstitial lung disease (RA-ILD) patients. The purpose of this study was to complete a systematic review and meta-analysis of the factors associated with mortality in RA-ILD patients. METHODS: Medline, EMBASE and the Cochrane Library were searched up to September 1, 2020. The Newcastle-Ottawa Scale (NOS) was applied to assess the methodological quality of the eligible studies. Study characteristics and magnitude of effect sizes were extracted. Then, pooled hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) and pooled risk ratios (RRs) with 95% CIs were calculated to assess the factors associated with mortality in RA-ILD. RESULTS: Twenty-three of 3463 articles were eligible, and ten factors associated with mortality for RA-ILD were evaluated in the meta-analysis. Older age (HRs = 1.04, 95% CI 1.03-1.05), male sex (HRs = 1.44, 95% CI 1.21-1.73), having a smoking history (HRs = 1.42, 95% CI 1.03-1.96), lower diffusing capacity of the lung for carbon monoxide (DLCO)% predicted (HRs = 0.98, 95% CI 0.97-1.00), forced vital capacity (FVC)% predicted (HRs = 0.99, 95% CI 0.98-1.00), composite physiological index (CPI) (HRs = 1.04, 95% CI 1.02-1.06), usual interstitial pneumonia (UIP) pattern on HRCT (HRs = 1.88, 95% CI 1.14-3.10 and RRs = 1.90, 95% CI 1.50-2.39), emphysema presence (HRs = 2.31, 95% CI 1.58-3.39), and acute exacerbation of ILD (HRs = 2.70, 95% CI 1.67-4.36) were associated with increased mortality in RA-ILD, whereas rheumatoid factor (RF) positive status was not associated. CONCLUSIONS: Through this systematic review and meta-analysis, we found that older age, male sex, smoking history, higher CPI, lower DLCO% predicted, lower FVC% predicted, UIP pattern on HRCT, emphysema presence and acute exacerbation of ILD were associated with an increased risk of mortality in RA-ILD.

Doctor's aptitude for switching from innovator etanercept to biosimilar etanercept in inflammatory rheumatic diseases: experience from a single French rheumatology tertiary care center.

OBJECTIVES: To describe the switch to biosimilar etanercept (bETN), evaluate factors associated with this switch, and evaluate the efficacy of this switch in a real-life setting METHODS: We included patients, from October 2016 to April 2017, with rheumatoid arthritis (RA) and spondyloarthritis (SpA) who received innovator ETN (iETN) for at least 6 months. After receiving information on biosimilars, all physicians were invited to propose a switch from iETN to bETN. Factors associated with bETN discontinuation were explored by univariate and multivariate analyses. We estimated the proportion of patients still on bETN over time by Kaplan-Meier survival analysis. We assessed serum trough concentrations of iETN and bETN and anti-drug antibodies to ETN. RESULTS: Overall, 183 outpatients were eligible for a potential switch; 94 (51.6%) switched from iETN to bETN. The probability of a switch was greater with an older than younger aged physician (mean [SD] age 50.4 [14.3] with a switch vs 44.8 [11.3] with no switch, p = 0.005) and the physician having a full-time academic position than other position (56.4% with a switch vs 13.5% with no switch, p < 0.001). After a 6-month follow-up, bETN retention rate was 83% (95% CI: 0.76-0.92). The first cause of bETN discontinuation was inefficacy (50%). On multivariate analysis, no factor was independently associated with a bETN switch or discontinuation. Drug trough levels did not significantly differ by discontinuation or continuation of bETN. No patient showed anti-drug antibodies. CONCLUSION: The probability of switching from iETN to bETN was likely related to physician characteristics.

Changing trends in rheumatoid arthritis mortality in Mexico, from 1998 to 2017.

The aim was to analyze the distribution and trends of deaths reported for rheumatoid arthritis (RA) in Mexico in 1998-2017. We carried out a cross-sectional study. Data were obtained from Dynamic Cubes, General Direction of Health Information, on deaths related to RA in Mexico. Seropositive RA was diagnosed using the International Classification of Diseases version 10. Variables were categorized by diagnosis, age, and gender. Time trends of age-standardized mortality rates (ASMRs) were analyzed for RA, and the annual percent change (APC) was estimated using Joinpoint trend analysis. We found 714 deaths mentioned as RA and 9,749,956 non-RA deaths between 1998 and 2017. Overall RA mortality decreased from 0.14 in 2004 to 0.04 per 100 000 in 2017 (APC: - 10.3%; 95% CI - 16.5%, - 3.3%), while the non-RA ASMR remained stable. In females, there was an initial increase of 27.3% per year through 1998-2004 and a reduction of - 11.7% per year subsequently, while in males, the APC remained stable between 1998 and 2017. The trend for RA mortality resulted in a cumulative change in the ratio of RA ASMR to non-RA ASMR of - 20.6% in females and + 3.2% in males. Although mortality attributable to RA increased from 1998 to 2004 in Mexico, it began to improve after 2004, particularly in females. Prospective, population-based data could help to identify risk factors that could be altered to improve outcomes.

Impact of rheumatoid arthritis on major cardiovascular events in patients with and without coronary artery disease.

INTRODUCTION: Rheumatoid arthritis (RA) is a risk factor for cardiovascular disease. The clinical consequences of coincident RA and coronary artery disease (CAD) are unknown. OBJECTIVE: We aimed to estimate the impact of RA on the risk of adverse cardiovascular events in patients with and without CAD. METHODS: A population-based cohort of patients registered in the Western Denmark Heart Registry, who underwent coronary angiography (CAG) between 2003 and 2016, was stratified according to the presence of RA and CAD. Endpoints were myocardial infarction (MI), major adverse cardiovascular events (MACE; MI, ischaemic stroke and cardiac death) and all-cause mortality. RESULTS: A total of 125 331 patients were included (RA: n=1732). Median follow-up was 5.2 years. Using patients with neither RA nor CAD as reference (cumulative MI incidence 2.7%), the 10-year risk of MI was increased for patients with RA alone (3.8%; adjusted incidence rate ratio (IRRadj) 1.63, 95% CI 1.04 to 2.54), for patients with CAD alone (9.9%; IRRadj 3.35, 95% CI 3.10 to 3.62), and highest for patients with both RA and CAD (12.2%; IRRadj 4.53, 95% CI 3.66 to 5.59). Similar associations were observed for MACE an all-cause mortality. CONCLUSIONS: In patients undergoing CAG, RA is significantly associated with the 10-year risk of MI, MACE and all-cause mortality regardless of the presence of CAD. However, patients with RA and CAD carry the largest risk, while the additive risk of RA in patients without CAD is minor. Among patients with RA, risk stratification by presence or absence of documented CAD may allow for screening and personalised treatment strategies.

Immunosuppression and the risk of readmission and mortality in patients with rheumatoid arthritis undergoing hip fracture, abdominopelvic and cardiac surgery.

OBJECTIVES: The impact of immunosuppression on postoperative outcomes has primarily been studied in patients undergoing joint replacement surgery. We aimed to evaluate the impact of biologics and glucocorticoids on outcomes after other major surgeries. METHODS: This retrospective cohort study used Medicare data 2006-2015 to identified adults with rheumatoid arthritis undergoing hip fracture repair, abdominopelvic surgery (cholecystectomy, hysterectomy, hernia, appendectomy, colectomy) or cardiac surgery (coronary artery bypass graft, mitral/aortic valve). Logistic regression with propensity-score-based inverse probability weighting compared 90-day mortality and 30-day readmission in patients receiving methotrexate (without a biologic or targeted synthetic disease-modifying antirheumatic drug (tsDMARD)), a tumour necrosis factor inhibitor (TNFi) or a non-TNFi biologic/tsDMARD <8 weeks before surgery. Similar analyses evaluated associations between glucocorticoids and outcomes. RESULTS: We identified 10 777 eligible surgeries: 3585 hip fracture, 5025 abdominopelvic and 2167 cardiac surgeries. Compared with patients receiving methotrexate, there was no increase in the risk of 90-day mortality or 30-day readmission among patients receiving a TNFi (mortality adjusted OR (aOR) 0.83 (0.67 to 1.02), readmission aOR 0.86 (0.75 to 0.993)) or non-TNFi biologic/tsDMARD (mortality aOR 0.78 (0.49 to 1.22), readmission aOR 1.02 (0.78 to 1.33)). Analyses stratified by surgery category were similar. Risk of mortality and readmission was higher with 5-10 mg/day of glucocorticoids (mortality aOR 1.41 (1.08 to 1.82), readmission aOR 1.26 (1.05 to 1.52)) or >10 mg/day (mortality aOR 1.64 (1.02 to 2.64), readmission aOR 1.60 (1.15 to 2.24)) versus no glucocorticoids, although results varied when stratifying by surgery category. CONCLUSIONS: Recent biologic or tsDMARD use was not associated with a greater risk of mortality or readmission after hip fracture, abdominopelvic or cardiac surgery compared with methotrexate. Higher dose glucocorticoids were associated with greater risk.

Trends in all-cause and cardiovascular mortality in patients with incident rheumatoid arthritis: a 20-year follow-up matched case-cohort study.

OBJECTIVES: To examine all-cause and cardiovascular disease (CVD) mortality in consecutive cohorts of patients with incident RA, compared with population comparators. METHODS: The Oslo RA register inclusion criteria were diagnosis of RA (1987 ACR criteria) and residency in Oslo. Patients with disease onset 1994-2008 and 10 matched comparators for each case were linked to the Norwegian Cause of Death Registry. Hazard ratios for all-cause and CVD mortality were calculated for 5, 10, 15 and 20 years of observation using stratified cox-regression models. Mortality trends were estimated by multivariate cox-regression. RESULTS: 443, 479 and 469 cases with disease incidence in the periods 94-98, 99-03 and 04-08 were matched to 4430, 4790 and 4690 comparators, respectively. For cases diagnosed between 1994 and 2003, the all-cause mortality of cases diverged significantly from comparators after 10 years of disease duration [hazard ratio (95% CI) 94-98 cohort 1.42 (1.15-1.75): 99-03 cohort 1.37 (1.08-1.73)]. CVD related mortality was significantly increased after 5 years for the 94-98 cohort [hazard ratio (95% CI) 1.86 (1.16-2.98) and after 10 years for the 99-03 cohort 1.80 (1.20-2.70)]. Increased mortality was not observed in the 04-08 cohort where cases had significantly lower 10-year all-cause and CVD mortality compared with earlier cohorts. CONCLUSION: All-cause and CVD mortality were significantly increased in RA patients diagnosed from 1994 to 2003, compared with matched comparators, but not in patients diagnosed after 2004. This may indicate that modern treatment strategies have a positive impact on mortality in patients with RA.

A long-term nationwide study on mortality associated to rheumatoid arthritis in Italy.

OBJECTIVES: We aimed to evaluate trends of rheumatoid arthritis (RA) mortality reported as the underlying cause of death (UCD) and as multiple causes of death (MCD) in Italy between 2003 and 2015. METHODS: Analyses were carried out on the Italian National Cause of Death Register, managed by the Italian National Institute of Statistics (ISTAT). Deaths from January 1, 2003 to December 31, 2015 with any mention of RA were included. Diseases are coded according to the International Classification of Diseases, 10th Edition (ICD- 10, 2009 version). Time trends of age-standardised rates were analysed for RA both as UCD and MCD, and the annual percent change (APC) was estimated. RESULTS: Overall, 26,564 deaths with a mention of RA were retrieved out of 7,595,214 deaths (0.35% of all certificates). The mention of RA as MCD increased throughout the study period, meanwhile the selection as the UCD decreased. RA mortality rates based on the UCD declined (males APC -3.1%, CI -3.9, -2.3; females APC -3.3%, CI -4.1, -2.4); while rates based on the MCD were stable. Specifically, rates were stable or declined among younger subjects and increased in subjects aged ≥80 years. CONCLUSIONS: RA was found to be increasingly reported in death certificates in the last two decades in Italy, although it is less frequently reported as the UCD. Due to the increased survival of patients, we observed a shift of RA-related mortality towards the elderly, making RA a comorbidity contributing to death in these patients.

Fibrosis-4 index at diagnosis can predict all-cause mortality in patients with rheumatoid arthritis: A retrospective monocentric study.

Objectives: Comorbidities and conventional risk factors influence the prognosis of patients with rheumatoid arthritis (RA). We investigated whether liver fibrosis burden is associated with all-cause mortality in patients with RA.Methods: A total of 2812 patients with RA were retrospectively selected and reviewed. Liver fibrosis was assessed using the fibrosis-4 index (FIB-4) [age (years)× aspartate aminotransferase level (IU/L)/platelet count (109/L)/√alanine aminotransferase (IU/L)].Results: The mean patient age was 51.5 years (482 men and 2330 women). The mean erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and FIB-4 were 43.5 mm/h, 9.0 mg/L, and 1.0, respectively. Methotrexate was used in 2524 (89.9%) patients, and biological or targeted synthetic disease-modifying antirheumatic drugs were used in 310 (11.0%) patients. During the follow-up period (mean 93.7 months), 89 (3.2%) patients died. Deceased patients had a significantly higher age (mean 64.4 vs. 51.1 years); frequency of male sex (31.5% vs. 16.7%), hypertension (HTN; 40.4 vs. 18.5%), and diabetes mellitus (DM; 25.8% vs. 7.7%); ESR (mean 57.1 vs. 43.0 mm/h); CRP (mean 16.9 vs. 8.7 mg/L); and FIB-4 (mean 1.5 vs. 1.0) (all p < .05) than the survivors. On multivariate analysis, higher FIB-4 was found to be independently associated with a higher rate of all-cause mortality (hazard ratio =1.130, p = .004), together with male sex, HTN, DM, ESR, and intensity of glucocorticoid exposure, whereas the use of methotrexate was independently protective (all p < .05).Conclusion: Besides conventional risk factors, fibrotic burden, assessed using FIB-4, might be useful for risk stratification of patients newly diagnosed as having RA.

Normal mortality of the COBRA early rheumatoid arthritis trial cohort after 23 years of follow-up.

OBJECTIVES: Mortality in patients with rheumatoid arthritis (RA) is higher than in the general population. We investigated mortality in the COBRA-trial cohort after 23 years follow-up, compared with a reference sample of the Dutch population. METHODS: The COBRA-trial randomised patients with early RA to sulfasalazine monotherapy (SSZ, n=79) or a combination of SSZ, low-dose methotrexate and initially high, step-down prednisolone (COBRA, n=76). We compared the mortality in the COBRA-trial up to 2017 to a reference sample of the general population in the Netherlands (standardised mortality ratio, SMR), and its relation to early prognostic factors through stepwise Cox regression. RESULTS: Duration of follow-up in patients alive was mean 23 (range 22-24) years. In total, 44 patients died (28%, SMR=0.80 [95% CI 0.59 to 1.06]); 20 of 75 COBRA patients (27%, SMR 0.75 [0.47 to 1.14]) and 24 of 79 SSZ patients (30%, SMR 0.85 [0.56 to 1.25]); p=0.61). In the reference sample of the general population, 55 people (36%) died. 5 factors were significantly associated with increased mortality hazard: damage progression at 28 weeks; high Health Assessment Questionnaire (HAQ) score and absence of HLA-DR 2 or 3; disease duration from start of complaints was also significant, but showed an uninterpretable pattern. CONCLUSIONS: This prospective trial cohort study of early RA is one of the first to show similar mortality compared with the general population after 23 years of follow-up. It confirms that early, intensive treatment of RA has long-term benefits and suggests that treating to target is especially important for patients with poor prognosis.