Incidence Of Rheumatoid Arthritis Research Articles

Atopic Dermatitis is a Risk Factor for Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

It is still unclear whether patients with atopic dermatitis (AD) have an increased risk of developing rheumatoid arthritis (RA). We aimed to investigate the association between AD and risk of RA using systematic review and meta-analysis. We searched Medline and EMBASE up to April 2021 using search strategy, including terms for "atopic dermatitis" and "rheumatoid arthritis." Eligible cohort study must compare the incidence of RA between patients with AD and comparators without AD. Eligible case-control study must recruit cases with RA and controls without RA. Then, the study must compare the prevalence of AD between the groups. Point estimates with standard errors from each study were combined using the generic inverse variance method. The meta-analysis found that AD patients had a significantly higher risk of incident RA than individuals without AD with a pooled odds ratio (OR) of 1.30 (95% confidence interval [CI], 1.17-1.44; I2, 48%). Subgroup analysis revealed a significantly higher risk of RA in cohort study subgroup (pooled OR, 1.37; 95% CI, 1.25-1.50; I2, 63%) but not case-control study subgroup (pooled OR, 0.99; 95% CI, 0.77-1.28; I2, 10%). This study found a significantly higher risk of incident RA among AD patients.

Tristetraprolin Gene Single-Nucleotide Polymorphisms and mRNA Level in Patients With Rheumatoid Arthritis.

To observe and evaluate the correlation between single-nucleotide polymorphisms (SNPs) and messenger RNA (mRNA) level related to tristetraprolin (TTP) in Chinese rheumatoid arthritis (RA). TapMan SNP was used for genotyping analysis in 580 RA patients and 554 healthy people. Association between TTP gene polymorphisms (rs251864 and rs3746083) and RA was obtained. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) technology was applied for the detection of TTP mRNA level in peripheral blood mononuclear cells (PBMCs) in 36 RA patients and 37 healthy people. We observed that the allele T of TTP rs3746083 increased RA susceptibility (p = 0.019). A significant difference was found under the dominant model of rs3746083 (p = 0.037). Further analysis showed the allele distribution of rs3746083 was nominally correlated with RF phenotype of RA patients (p = 0.045). Nevertheless, the association between TTP rs251864 and the incidence of RA was no statistically significant (p > 0.05). The TTP expression level in PBMCs of RA patients was significantly reduced (p < 0.001). In conclusion, the results of this experiment support that TTP may be involved in the pathogenesis of RA.

Incidence, sociodemographic factors and treatment penetration of rheumatoid arthritis and psoriatic arthritis in Norway

ObjectivesTo evaluate nationwide incidence, sociodemographic associations and treatment penetration of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in Norway. MethodsThe study combined data from nationwide registries on the total Norwegian adult population (age ≥ 18). From the Norwegian Patient Registry, incident RA and PsA cases during 2011–2015 were identified with records of first and second healthcare episodes listing RA/PsA diagnostic codes, and ≥ 1 episode in an internal medicine or rheumatology unit with RA/PsA code during the two-year period after the first episode. Dispensed DMARD prescriptions were obtained from the Norwegian Prescription Database. Persons with dispensed DMARD prescriptions or biologic DMARDs given in hospitals > 12 months before the index date were excluded. ResultsIncidence of RA/PsA in Norway was 42/26 per 100,000 person-years (55/28 among women and 28/23 among men). RA peak incidence was observed at ages 70–79 in both sexes, whereas the peak incidence of PsA occurred at ages 50–59. Age- and sex-standardized incidences of RA and PsA were lower among persons with higher education levels. Within a year from the index date, 82.4/57.4% of RA/PsA patients used synthetic DMARDs while 9.4/9.5% used biologic DMARDs. ConclusionsRegister-based incidence estimates for RA and PsA in Norway are similar to other Nordic countries, but slightly higher than in previous Norwegian studies. Furthermore, we found that higher socioeconomic status was associated with lower incidence of both RA and PsA. Although conventional synthetic DMARDs were less often used in early PsA than RA, frequency of biologic DMARD prescriptions was comparable.

Epidemiological Trends of Rheumatoid Arthritis and PADI4, PTPN22, and HLA-DRB9 Genes Distribution in the Kazakhstan Population

BACKGROUND: The prevalence of rheumatoid arthritis (RA) is 1% in the global population. The lack of epidemiological studies in developing countries makes it difficult to obtain a complete global epidemiological picture of RA. RA develops due to the interaction of multiple genetic and environmental factors, though the contribution of these factors to the various disease occurrence seen in different populations is unclear. AIM: The aim of our study was to analyze the dynamics of the general prevalence and incidence of RA among the population of Kazakhstan in 2017–2019 as well as to investigate the three most common single-nucleotide polymorphisms (SNP) of RA in the Kazakhstan population. METHODS: The analysis of statistical data on Form 12 “On the health of the people and the health care system” was carried out. Prevalence and incidence rates were calculated according to generally accepted rules. Demographic data for the Republic of Kazakhstan were obtained from the official website stat.gov.kz. Our study included 70 RA patients and 113 control subjects. Blood samples were collected and genotyped for peptidylarginine deiminase 4 (PADI4), protein tyrosine phosphatase 22, and human leukocyte antigen (HLA)-DRB9 SNPs by reverse transcription polymerase chain reaction. RESULTS: The prevalence of RA in Kazakhstan in 2017–2019 was 0.36–0.38%, with an incidence rate of 0.085–0.087%, which can be comparable to data of other countries in Central Asia. The allele and genotypes frequency analyses were carried out between patients and controls. The HLA-DRB9 showed significant association of the G allele odds ratio (OR) 1.96 (95% confidence interval [CI]: 1.252–3.081), p= 0.0025 and G/G genotype OR = 3.67 (95% CI: 1.58–8.54), p = 0.00162 with RA in our sample. Strong association between anti-citrullinated protein antibody (ACPA) profile and PADI4 (OR 12.19 [95% CI: 2.19–67.94], p = 0.00115) was found. CONCLUSION: There was an increase in RA prevalence with age among females and a higher crude prevalence and incidence of RA in the southern regions of Kazakhstan. HLA-DRB9 prevailed in Kazakhstani patients with RA, PADI4 showed association with ACPA-positive RA. Further studies on larger samples are required to confirm our obtained results.

Is tea consumption associated with reduction of risk of rheumatoid arthritis? A Swedish case-control study

BackgroundTea is a popular beverage around the world and has properties that can affect the immune system. The association between tea consumption and the risk of rheumatoid arthritis (RA), a chronic autoimmune disease primarily affecting the joints, is not well studied and results are conflicting.MethodsWe collected data on tea consumption for 2237 incident RA cases diagnosed 2005–2018 and 4661 controls matched on age, sex, and residential area. Tea consumption was classified into no (0 cups/day), irregular (< 1 cup/day), regular (1–2 cups/day), and high (≥ 2 cups/day) consumption, and irregular consumption was used as the reference category. Missing data on tea consumption was classified as no consumers, and sensitivity analyses were performed to test this assumption. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, adjusting for smoking, coffee, alcohol, educational level, and body mass index. We also performed stratified analysis on sex, anti-citrullinated autoantibody (ACPA) status, and smoking habits.ResultsAmong the cases, we found 57.3% to be ever consumers of tea with 19.7 having a high tea consumption. Corresponding figures for the controls were 58.4% ever drinkers with 22.1% high tea consumers. High tea consumption had an inverse association to the risk of RA compared to irregular consumption [OR = 0.78 (95% CI 0.66–0.92)], but the association lost statistical significance in the adjusted model [adjusted OR (adjOR) = 0.85 (95% CI 0.71–1.01)]. Among non-tea consumers, a protective effect was also observed compared to irregular consumers [adjOR = 0.82 (95% CI 0.70–0.88)], but this association did not withstand sensitivity analysis, possibly due to bias. In the ACPA-positive group and among current smokers, a protective effect of tea consumption was observed among the high tea consumers [adjOR = 0.76 (95% CI 0.62–0.94) and adjOR = 0.60 (95% CI 0.38–0.95), respectively].ConclusionsThis study suggests a protective effect of high consumption of tea, among smokers and for ACPA-positive RA.Trial registrationNot applicable

Risk Factors for Diagnosis of Psoriatic Arthritis, Psoriasis, Rheumatoid Arthritis, and Ankylosing Spondylitis: A Set of Parallel Case-control Studies.

To compare potential risk factors for the diagnosis of psoriatic arthritis (PsA), psoriasis (PsO), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Four parallel case-control studies were conducted within The Health Improvement Network using data between 1994 and 2015. Patients with PsA, PsO, RA, or AS were identified using validated code lists and matched to controls on age, sex, practice, and year. Risk factors were selected in the time prior to diagnosis. Multivariable logistic regression models were constructed for each disease using automated stepwise regression to test potential risk factors. Patients with incident PsA (n = 7594), PsO (n = 111,375), RA (n = 28,341), and AS (n = 3253) were identified and matched to 75,930, 1,113,345, 283,226, and 32,530 controls, respectively. Median diagnosis age was 48 (IQR 38-59), 43 (IQR 28-60), 60 (IQR 48-71), and 41 (IQR 32-54) years, respectively. In multivariable models, there were some shared and some differing risk factors across all 4 diseases: PsA was associated with obesity, pharyngitis, and skin infections; PsA and PsO were associated with obesity and moderate alcohol intake; PsA and AS were associated with uveitis; and PsA and RA were associated with preceding gout. Both RA and AS were associated with current smoking, former moderate drinking, anemia, osteoporosis, and inflammatory bowel disease. All shared former or current smoking as a risk factor; statin use was inversely associated with all 4 diseases. Shared and different risk factors for PsA, PsO, RA, and AS were identified. Statin use was inversely associated with all 4 conditions.

Assessing improved risk prediction of rheumatoid arthritis by environmental, genetic, and metabolomic factors

ObjectiveWe sought to improve seropositive rheumatoid arthritis (RA) risk prediction using a novel weighted genetic risk score (wGRS) and preclinical plasma metabolites associated with RA risk. Predictive performance was compared to previously validated models including RA-associated environmental factors. MethodsThis nested case-control study matched incident seropositive RA cases (meeting ACR 1987 or EULAR/ACR 2010 criteria) in the Nurses’ Health Studies (NHS) to two controls on age, blood collection features, and post-menopausal hormone use at pre-RA blood draw. Environmental variables were measured at the questionnaire cycle preceding blood draw. Four models were generated and internally validated using a bootstrapped optimism estimate: (a) base with environmental factors (E), (b) environmental, genetic and gene-environment interaction factors (E + G + GEI), c) environmental and metabolic factors (E + M), and d) all factors (E + G + GEI + M). A fifth model including all factors and interaction terms was fit using ridge regression and cross-validation. Models were compared using area under the receiver operating characteristic curve (AUC). Results150 pre-RA cases and 455 matched controls were included. The E model yielded an optimism-corrected AUC of 0.622. The E + M model did not show improvement over the E model (corrected AUC 0.620). Including genetic factors increased prediction, producing corrected AUCs of 0.677 in the E + G + GEI model and 0.674 in the E + G + GEI + M model. Similarly, the performance of the cross-validated ridge regression model yielded an AUC of 0.657. ConclusionAddition of wGRS and gene-environment interaction improved seropositive RA risk prediction models. Preclinical metabolite levels did not significantly contribute to prediction.

Single Nucleotide Polymorphism rs2075876 in AIRE Gene is a Strong Rheumatoid Arthritis Determinant

Rheumatoid arthritis (RA) is a progressive and common autoimmune disease with multifactorial etiology. Several pieces of research show that genetic factors play a major role in the incidence of RA. Several genome-wide association studies (GWAS) have identified the autoimmune regulator (AIRE) gene as one of the candidate loci. This gene encodes a transcription factor, which is involved in the presentation of self-antigens and the negative selection of self-reactive T-cells in the thymus. Studies have indicated that single nucleotide polymorphisms (SNPs) in the AIRE gene can change the gene expression and/or function. In the present study, we assessed the possible association between SNP rs2075876 (intronic variant) in the AIRE gene with RA risk in the Iranian population. A case-control study using 56 RA patients and 58 control subjects was undertaken to evaluate rs2075876 genotypes using the real-time PCR high resolution melting method (HRM). Logistic regression analysis demonstrates that homozygous AA and heterozygous AG genotypes compared with GG genotype increase the risk of RA (AA vs. GG; OR=16.43; 95% CI [5.33-50.71] and AG vs. GG; OR=3.21; 95% CI [1.22-8.45]). Also, individuals with allele A were more frequently affected with RA than subjects with G allele (OR=5.81; 95% CI [3.28-10.30]). Furthermore, in the patient group, we found a significant correlation between erythrocyte sedimentation rate and C-reactive protein concentration with rs2075876 polymorphism (P&lt;0.05). Our findings propose a substantial correlation between rs2075876 polymorphism and RA risk.

No difference in antidepressant prescription in rheumatoid arthritis and controls. Results from a population-based, matched inception cohort

Objective: Depression occurs at least two times more often in rheumatoid arthritis (RA) patients than in controls, but little is known about the treatment of depression in RA. The primary objective of this study was to compare the 1 year period prevalence of antidepressant prescription in patients with RA versus controls. Method: We included a retrospective inception cohort of 509 patients with incident RA and 2545 frequency-matched population controls ascertained from 1995 to 2002. The cohort was followed until 31 December 2017 and linked with nationwide Danish registers. From the Danish National Prescription Register, we obtained information on redeemed prescriptions of antidepressants (Anatomical Therapeutic Chemical code N06A). Results: We did not demonstrate significant differences in the 1 year period prevalence ratios and the incidence rate ratios for either antidepressant prescription or the frequency of hospital admissions with depressive episode. The most frequent indication for antidepressant prescription in patients with RA was depression. Cox regression analyses showed no association between RA and antidepressant prescription. Conclusion: We found no significant differences in the occurrence of antidepressant prescription in patients with RA versus matched controls. The main indication for antidepressant prescription in RA was depression.

Alcohol Consumption and Risk of Rheumatoid Arthritis among Chinese Adults: A Prospective Study.

Alcohol consumption may be associated with the risk of rheumatoid arthritis (RA), but potential sex-related differences in this association have not been explored. Thus, we utilized 87,118 participants in the Kailuan Study, a prospective cohort initiated in 2006 to study the risk factors of cardiovascular disease in a Chinese population. We included those that did not have RA at baseline (2006), and performed cox proportional hazard modeling to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) of RA according to the levels of alcohol consumption (never or past, light or moderate (<1 serving/day for women, <2 servings/day for men), and heavy (>1 serving/day for women, >2 servings/day for men), adjusting for age, sex, body mass index, and smoking. Diagnoses of RA were confirmed via medical record review by rheumatologists. From 2006 to 2018, we identified 87 incident RA cases. After adjusting for potential confounders, the HR of RA was 1.26 (95% CI: 0.62, 2.56) for participants with light or moderate alcohol consumption and 1.98 (95% CI: 0.93, 4.22) for participants with heavy alcohol consumption) versus non-drinkers. The HR of each 10 g increase in alcohol consumption was 1.11 (95% CI: 0.98, 1.26) (p-trend = 0.09). A significant association between alcohol consumption and RA risk was observed in women, but not in men (p for interaction = 0.06). Among women, each 10 g increase in alcohol consumption was significantly associated with a high risk of RA (HR: 1.56; 95% CI: 1.06, 2.29). In contrast, each 10 g increase in alcohol consumption was not significantly associated with the risk of RA in men (HR: 1.10; 95% CI: 0.97, 1.25). Excluding past drinkers generated similar results. In this prospective Chinese cohort, increasing alcohol consumption was associated with an elevated risk of RA among women, but not in men. These findings highlight the importance of incorporating analysis of sex differences into future studies of alcohol consumption and RA risk.

Association Between Immunosuppressive Therapy and Incident Risk of Interstitial Lung Disease in Systemic Sclerosis

Association Between Immunosuppressive Therapy and Incident Risk of Interstitial Lung Disease in Systemic Sclerosis

Trends in incidence of dementia among patients with rheumatoid arthritis: A population-based cohort study

ObjectiveWe aimed to assess the incidence of dementia over time in patients with incident rheumatoid arthritis (RA) as compared to non-RA referents. MethodsThis population-based, retrospective cohort study included Olmsted County, Minnesota residents with incident RA by ACR 1987 criteria, diagnosed between 1980 and 2009. We matched non-RA referents 1:1 on age, sex, and calendar year and followed all individuals until 12/31/2019. Incident dementia was defined as two codes for Alzheimer's disease and related dementias (ADRD) at least 30 days apart. Cumulative incidence of ADRD was assessed, adjusting for the competing risk of death. Cox proportional hazards models calculated hazard ratios (HR) with 95% confidence intervals (CI) for incident ADRD by decade. ResultsAfter excluding individuals with prior dementia, we included 897 persons with incident RA (mean age 56 years; 69% female) and 885 referents. The 10-year cumulative incidence of ADRD in individuals diagnosed with RA during the 1980s was 12.7% (95%CI:7.9–15.7%), 1990s was 7.2% (95%CI:3.7–9.4%), and 2000s was 6.2% (95%CI:3.6–7.8%). Individuals with RA diagnosed in 2000s had insignificantly lower cumulative incidence of ADRD than those in the 1980s (HR 0.66; 95%CI:0.38–1.16). The overall HR of ADRD in individuals with RA was 1.37 (vs. referents; 95%CI:1.04–1.81). When subdivided by decade, however, the risk of ADRD in individuals diagnosed with RA was higher than referents in the 1990s (HR 1.72, 95%CI:1.09–2.70) but not 2000s (HR 0.86, 95%CI:0.51–1.45). ConclusionsThe risk of dementia in individuals with RA appears to be declining over time, including when compared to general population referents.

A systematic review and meta-analysis of observational studies on the association between animal protein sources and risk of rheumatoid arthritis

The aim of this study was to investigate the linear and nonlinear dose-response associations of animal-based dietary protein intake and risk of developing rheumatoid arthritis (RA). A systematic search of MEDLINE, Scopus and Embase was conducted up to October 2020. Observational studies that report risk estimates of RA for animal-based protein consumption were included. We calculated pooled relative risks (RRs) by using a random-effects model. Linear and non-linear dose-response analyses were performed to examine the dose-response relations between animal-based protein consumption and RA. Seven cohort studies (n=457,554) with 3545 incident cases and six case-control studies with 3994 cases and 5252 controls were identified. Highest compared with the lowest category of fish consumption was inversely associated with risk of RA (RR: 0.89; 95% CI, 0.80 to 0.99; I2=0%, n=10). Also, a 100g/day increment in fish intake was associated with a 15% decreased risk of RA. Dose-response analysis showed a modest U-shaped association between fish consumption and incidence of RA, with the lowest risk at a fish intake of 20-30g/day (Pnon-linearity=0.04). We found no significant association between consumption of red meat, poultry or dairy and the risk of RA. The present study revealed a significant reverse association between fish consumption and risk of RA. While we observed no association between red meat, dairy or poultry consumption and risk of RA. Further well-designed prospective studies are needed to support our findings.

Bidirectional association between migraine and rheumatoid arthritis: two longitudinal follow-up studies with a national sample cohort

ObjectiveTo investigate the bidirectional association between migraine and rheumatoid arthritis (RA).DesignTwo longitudinal follow-up studies.SettingData collected from a national cohort between 2002 and 2013 by the Korean National Health Insurance Service-Health...

Association of biological antirheumatic therapy with risk for type 2 diabetes: a retrospective cohort study in incident rheumatoid arthritis

ObjectiveTo explore possible associations of treatment with biological disease-modifying antirheumatic drugs (bDMARDs), including T-cell-based and interleukin-6 inhibition (IL-6i)-based therapies, and the risk for type 2 diabetes mellitus (T2DM) in patients...

POS0029 INCIDENCE AND TREATMENT PENETRATION OF RHEUMATOID ARTHRITIS IN NORWAY – A NATIONWIDE REGISTER LINKAGE STUDY

Background:Incidence of rheumatoid arthritis (RA) in Norway has not been evaluated in a nationwide setting.Objectives:To estimate the incidence of RA and real-life penetration of disease-modifying antirheumatic drug (DMARD) use in Norway.Methods:The Norwegian Cardio-Rheuma register comprises pseudonymized data from nationwide registries including the total Norwegian population ≥18 years during 2008-2017. Demographic and socioeconomic data were retrieved from the National Population Register and Statistics Norway. Data on public or private somatic specialized care episodes were collected from the Norwegian Patient register (NPR) (ICD-10 codes for diagnoses and medical procedure codes for biologic DMARD infusions). Dispensed DMARD prescriptions were captured from the Norwegian Prescription Database. RA cases were defined as persons with NPR records of all of the following: 1) 1st episode with ICD-10 code M05/M06 as main or contributory diagnosis (index date), 2) 2nd episode with code M05/M06 within 2-year period following index date, 3) M05/M06 recorded in an internal medicine or rheumatology department during the 2-year period. Years 2008-2010 served as a look-back period to identify prevalent RA cases. To estimate person-years (pyrs) at risk, we calculated number of persons aged ≥ 18 living in Norway on the 1st of January of each year 2011-2015 and multiplied it by one year (prevalent RA cases excluded). Standardized estimates were calculated with 5-year age groups using Norwegian adult population 1st of January 2015 as the standard.Results:Between 2011 and 2015, 9,493 persons fulfilled the RA definition (62.4% seropositive based on ICD-10 codes). Incidence rate was 49/100,000 pyrs (32 in men and 65 in women). A sensitivity analysis excluding cases who had dispensed DMARDs &gt;12 months before index date yielded 8,125 RA cases (incidence 42/100,000 pyrs). Whereas absolute number of incident cases was highest among those aged 60-69 in both sexes, incidence was highest among those aged 70-79 (Figure 1). Both crude and age- and sex-standardized incidences were lower among persons with higher education level (crude/standardized incidence per 100,000 pyrs for those below upper secondary education 60/57; upper secondary or post-secondary non-tertiary education 53/52; higher education 36/39). Of incident cases, 94% received any DMARD treatment or glucocorticoids, 78% methotrexate, and 17% biologic DMARDs within 2 years after index date (Table 1).Conclusion:Contemporary register-based estimate of RA incidence in Norway is comparable to other Nordic countries.1,2 In line with treatment recommendations, methotrexate is the most commonly used DMARD in the initial treatment strategy in Norway. One in six patients used a biologic DMARD within 2 years from 1st recorded RA diagnosis.

Single nucleotide polymorphism rs5029937 in TNFAIP3 gene is correlated with risk of rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a progressive and common autoimmune disease with multifactorial etiology. Several pieces of research show that genetic factors play a major role in the incidence of RA. Several genome-wide association studies (GWAS) have identified the tumor necrosis factor alpha inducible protein 3 (TNFAIP3) genes as one of the candidate loci. The TNFAIP3 gene encoding ubiquitin-editing protein A20 witch restricts B cell survival and prevents autoimmunity. Previous studies have indicated that single nucleotide polymorphisms (SNPs) in the TNFAIP3 gene are correlated with several autoimmune disorders. In the present study, we assessed the possible association between SNP rs5029937 (intronic variant) in the TNFAIP3 gene with RA risk in the Iranian population. Methods: A case-control study using 50 RA patients and 50 control subjects was undertaken to evaluate rs5029937 (G>T) genotypes using real-time PCR high resolution melting method (HRM). The SPSS22 was used for statistical analyses and the significance level was set at P<0.05. Results: Logistic regression analysis demonstrates that homozygous TT + heterozygous TG genotypes compared with GG genotype increase the risk of RA (TT+TG vs GG; P= 0.004, OR= 3.46; 95%CI [1.492-8.075]). Also, individuals with allele T were more frequently affected with RA than subjects with G allele (T vs G; P= 0.004, OR= 2.61; 95%CI [1.382-4.919]). Conclusion: Our findings propose a substantial correlation between rs5029937 (G>T) polymorphism and RA risk in Iranian population.

Elevated Anti-Citrullinated Protein Antibodies Prior to Rheumatoid Arthritis Diagnosis and Risks for Chronic Obstructive Pulmonary Disease or Asthma.

To investigate elevation of anti-citrullinated protein antibodies (ACPAs) before diagnosis of rheumatoid arthritis (RA) and risks for chronic obstructive pulmonary disease (COPD) or asthma. We performed a matched cohort study nested within the Nurses' Health Studies among women who donated blood. Women with incident RA after blood draw (self-reported, then confirmed by medical records) were each matched to 3 controls by age, cohort, year, and menopausal factors. Pre-RA ACPA positivity was defined as >99th percentile of control distribution by a research assay or by cyclic citrullinated peptide in a subset. Incident COPD and asthma after index date (date of blood draw) were identified by questionnaires. Cox regression estimated hazard ratios (HRs) for incident COPD or asthma (in separate analyses) associated with pre-RA, pre-RA ACPA+, or pre-RA ACPA- phenotypes each compared to their matched non-RA controls. We analyzed 283 women who were pre-RA and 842 controls; blood was donated a mean ± SD of 9.7 ± 5.8 years before RA diagnosis. Fifty-nine women (20.8%) were pre-RA ACPA+. There were 107 cases of incident COPD and 105 incident asthma cases during 21,489 person-years of follow-up. Pre-RA ACPA+ was associated with increased COPD risk (HR 3.04 [95% confidence interval (95% CI) 1.33-7.00]) after adjusting for covariates including smoking pack-years. Pre-RA ACPA+ had an HR for asthma of 1.74 (multivariable 95% CI 0.72-4.24), similar to the risk of asthma for pre-RA ACPA- (HR 1.65 [95% CI 1.11-2.46]). Women with elevated ACPA before RA diagnosis had increased risk for developing COPD compared to controls. Women who later developed RA were more likely to develop asthma than controls, regardless of pre-RA ACPA status.

Association between chronic obstructive pulmonary disease, smoking, and interstitial lung disease onset in rheumatoid arthritis.

In rheumatoid arthritis (RA), respiratory manifestations include chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). We assessed whether baseline COPD and smoking were associated with RA-ILD onset. We identified new-onset ILD in incident RA subjects within the MarketScan Commercial Claims database, using physician and/or hospitalisation diagnostic codes. Smoking data (current, past, never) were available for a subset via a health questionnaire. Kaplan-Meier analyses assessed time to ILD onset, stratified by prior COPD and smoking. Multivariate Cox regression models were adjusted for age, sex, and (in the subset) smoking. Sensitivity analyses adjusted for past RA drugs. Among 373,940 new RA subjects, 6343 (1.7%) developed ILD (8.1 events per 1000 person-year, 95% CI 7.9, 8.3). ILD was more common among subjects with baseline COPD. Adjusting for age and sex, the hazard ratio (HR) between baseline COPD and incident ILD was 2.15, 95% CI 1.93, 2.39. We could not establish a clear relationship between current smoking and ILD; in the subset with smoking data, the HR point estimate for COPD was similar but the 95% CI was wider (due to fewer subjects) and included the null value. Adjusting for baseline RA drugs did not change results. Pre-existing COPD in incident RA subjects was associated with higher risk of future ILD. While a trend persisted after adjusting for smoking, we were limited by reduced sample size. Our study highlights the importance of ongoing assessments of potentially complicated relationships between smoking, COPD, and other factors in RA-associated ILD.

Periodontitis as a Risk Factor for Rheumatoid Arthritis: a Matched-Cohort Study

ObjectiveThe intent was to analyse the association of periodontitis with the development of rheumatoid arthritis (RA) using a representative population-based cohort and longitudinal matched-cohort design. MethodsParticipants were 40 years of age or older and had not been diagnosed with RA between 2002 and 2006. Among the participants, those who were newly diagnosed with periodontitis between 2004 and 2006 (excluding cases that had already been diagnosed with periodontitis between 2002 and 2003) were allotted to the periodontitis group. Among the participants, those who had never been diagnosed with periodontitis between 2002 and 2006 formed the control group, matched by sex, age, and household income at a 1:1 ratio. From 2007 to 2018, the 2 groups (n = 691,506) were followed to monitor the development of RA. The t-test and χ2 test compared the general characteristics and health-related variables of both groups. The Kaplan-Meier method with a log-rank test was conducted to compare the incidence of RA in both groups. The hazard ratio (HR) and adjusted hazard ratio (aHR) were calculated using a Cox proportional hazard regression analysis to evaluate the risk of subsequent RA. ResultsUnivariate analysis revealed that the periodontitis group was more likely to develop RA than the control group (hazard ratio 1.10), and multivariate analysis also revealed a higher incidence risk of RA (adjusted hazard ratio 1.09) in the periodontitis group. ConclusionsOur findings demonstrate that periodontitis is associated with an increased risk of developing RA.