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Association between ischemic stroke and seropositive rheumatoid arthritis in Korea: A nationwide longitudinal cohort study.

ABSTRACT: The purpose of this longitudinal follow-up study was to investigate the risk of ischemic stroke nationwide in patients with seropositive rheumatoid arthritis (RA) and controls who were matched in age and sex. Patient data were collected from the National Health Insurance Service (NHIS) Health Screening (HEALS) cohort. Using the International Classification of Diseases code M05 (seropositive RA), with a prescription of any disease-modifying anti-rheumatic drug (DMARD), RA was identified. A total of 2,765 patients and 13,825 control subjects were included in our study. The 12-year incidence of ischemic stroke in each group was calculated using the Kaplan-Meier method. The risk ratio of ischemic stroke was estimated using Cox proportional hazards regression. Sixty-four patients (2.31%) in the seropositive RA group and 512 (3.70%) in the control group experienced ischemic stroke (P < 0.001) during the follow-up period. The hazard ratio of ischemic stroke in the seropositive RA group was 1.32 (95% confidence interval (CI), 1.02-1.73) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in the seropositive RA group was 1.40 (95% CI, 1.07-1.82) after adjusting for demographics and comorbid medical disorders. According to the subgroup analysis, the hazard ratios of ischemic stroke risks in the female and hypertensive subgroups were 1.44 (95% CI, 1.05-1.97) and 1.66 (95% CI, 1.16-2.38), respectively. In the non-diabetes and non-dyslipidemia subgroups, the corresponding hazard ratios of ischemic stroke were 1.47 (95% CI, 1.11-1.95) and 1.43 (95% CI, 1.07-1.91). Seropositive RA patients have an increased risk of ischemic stroke. In female, hypertension, non-diabetes, and non-dyslipidemia RA subgroups, even without the traditional risk factors for stroke (except for hypertension), increased the risk, which could be potentially attributed to RA.

SUBMITTER: Lee DH

PROVIDER: S-EPMC8128246 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:We investigated the mortality and disability rate, as well as the healthcare expenditure, for patients with newly diagnosed seropositive rheumatoid arthritis (RA) who were followed-up for up to 10 years, compared to the general population in Korea. METHODS:We conducted a nationwide population-based study using a National Health Insurance Service-National Sample Cohort of the Korean population, consisting of 1 million individuals who submitted medical care claims between 2002 and 2013. RA was identified using as the International Classification of Diseases code M05 (seropositive RA), with prescription of any disease-modifying anti-rheumatic drug (DMARD). Our analysis was based on the data of 1655 patients with incident seropositive RA and 8275 non-RA controls. The controls were matched to the RA cohort by sex, age at the time of diagnosis, duration of follow-up, geographic region, type of social security, and household income. RESULTS:The most commonly used conventional synthetic DMARDs were hydroxychloroquine (71.30%) and methotrexate (69.5%), with adalimumab being the most commonly used biologic DMARD (2.54%). The mortality rate was significantly higher in the RA than the control group (incidence rate ratio [IRR] 1.29, 95% confidence interval [CI] 1.02-1.64) in the first 10 years after diagnosis. Specifically, mortality due to infectious diseases (IRR 4.41, 95% CI 1.60-12.17) and pneumonia (IRR 3.92, 95% CI 1.46-10.53) was significantly higher in the RA than control group. The disability rate was higher in the RA than control group over the first 10 years of the disease (IRR 2.27, 95% CI 1.77-2.92), which was attributed to a higher incidence of physical disability (IRR 3.81, 95% CI 2.81-5.15). Annual health expenditure was greater for the RA than the control group. CONCLUSIONS:Therefore, the rate of mortality and disability, as well as healthcare expenditure, are higher for patients with RA over the first 10 years of the disease onset, than the general population of Korea. The use of claim data has limited the quality of information and there is a limit to the observation period, and we expect the prospective national-wide multicenter cohort for longer period to overcome these limitations.

Project description:Background There is limited information regarding disease-modifying antirheumatic drug (DMARD)-dependent risks of overall, incident, and recurrent herpes zoster (HZ) during first-line biologic DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD) treatment among patients with seropositive rheumatoid arthritis (RA) in terms of HZ risk. Methods A total of 11,720 patients with seropositive RA who were prescribed bDMARD or tofacitinib between January 2011 and January 2019 from the Korean Health Insurance Review & Assessment Service database were studied. A multivariate Cox proportional hazards regression model was adopted to evaluate the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for the risk of HZ dependent on the choice of first-line bDMARDs or tsDMARD, including etanercept, infliximab, adalimumab, golimumab, tocilizumab, rituximab, tofacitinib, and abatacept. Results During the 34,702 person-years of follow-up, 1686 cases (14.4%) of HZ were identified, including 1372 (11.7%) incident and 314 (2.7%) recurrent HZs. Compared with that of the abatacept group, tofacitinib increased the overall risk (aHR, 2.46; 95% CI, 1.61–3.76; P<0.001), incidence (aHR, 1.99; 95% CI, 1.18–3.37; P=0.011), and recurrence (aHR, 3.69; 95% CI, 1.77–7.69; P<0.001) of HZ. Infliximab (aHR, 1.36; 95% CI, 1.06–1.74; P=0.017) and adalimumab (aHR, 1.29; 95% CI, 1.02–1.64; P=0.032) also increased the overall HZ risk. Moreover, a history of HZ was found to be an independent risk factor for HZ (aHR, 1.54; 95% CI, 1.33–1.78; P<0.001). Conclusions HZ risk is significantly increased in RA patients with a history of HZ after the initiation of bDMARDs or tsDMARD. The risk of incident and recurrent HZ was higher after tofacitinib treatment in patients with RA than that after treatment with bDMARDs. Individualized characteristics and history of HZ should be considered when selecting bDMARDs or tsDMARD for RA patients considering HZ risks. Supplementary Information The online version contains supplementary material available at 10.1186/s13075-022-02871-1.

Project description:ObjectivePatients with rheumatoid arthritis (RA) are at an increased risk of ischemic stroke. Tumor necrosis factor inhibitors (TNFi) may influence risk and mortality after ischemic stroke by reducing inflammation. This study was undertaken to examine the association of TNFi with the risk of incident ischemic stroke and with 30-day and 1-year mortality after ischemic stroke.MethodsPatients with RA starting therapy with TNFi and a biologics-naive comparator group treated with synthetic disease-modifying antirheumatic drugs (DMARDs) only were recruited to the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis from 2001 to 2009. Patients were followed up via clinical and patient questionnaires as well as the national death register. Incident strokes were classified as ischemic if brain imaging reports suggested ischemia or if ischemic stroke was reported as the underlying cause of death on a death certificate. Patients with a previous stroke were excluded. Risk of ischemic stroke was compared between patients receiving synthetic DMARDs only and those ever-exposed to TNFi using a Cox proportional hazards regression model adjusted for potential confounders. Mortality after ischemic stroke was compared between synthetic DMARD-treated patients and TNFi-treated patients using logistic regression, adjusted for age and sex.ResultsTo April 2010, 127 verified incident ischemic strokes (21 in 3,271 synthetic DMARD-treated patients and 106 in 11,642 TNFi-treated patients) occurred during 11,973 and 61,226 person-years of observation, respectively (incidence rate 175 versus 173 per 100,000 person-years). After adjustment for confounders, there was no association between ever-exposure to TNFi and ischemic stroke (hazard ratio 0.99 [95% confidence interval (95% CI) 0.54-1.81]). Mortality 30 days or 1 year after ischemic stroke was not associated with concurrent TNFi exposure (odds ratio 0.18 [95% CI 0.03-1.21] and 0.60 [95% CI 0.16-2.28], respectively).ConclusionExposure to TNFi does not appear to influence the occurrence of ischemic stroke in the medium term in patients with RA. The impact on mortality after ischemic stroke remains inconclusive.

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Association between ischemic stroke and seropositive rheumatoid arthritis in Korea: A nationwide longitudinal cohort study.

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