Age Of Rheumatoid Arthritis Onset Research Articles

The prevalence and risk factors of rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis

Background Interstitial lung disease (ILD) is the most widespread and fatal pulmonary complication of rheumatoid arthritis (RA). Existing knowledge on the prevalence and risk factors of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is inconclusive. Therefore, we designed this review to address this gap. Materials and Methods To find relevant observational studies discussing the prevalence and/or risk factors of RA-ILD, EMBASE, Web of Science, PubMed, and the Cochrane Library were explored. The pooled odds ratios (ORs) / hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated with a fixed/ random effects model. While subgroup analysis, meta-regression analysis and sensitivity analysis were carried out to determine the sources of heterogeneity, the I2 statistic was utilized to assess between-studies heterogeneity. Funnel plots and Egger’s test were employed to assess publication bias. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, our review was conducted. Results A total of 56 studies with 11,851 RA-ILD patients were included in this meta-analysis. The pooled prevalence of RA-ILD was 18.7% (95% CI 15.8–21.6) with significant heterogeneity (I2 = 96.4%). The prevalence of RA-ILD was found to be more likely as a result of several identified factors, including male sex (ORs = 1.92 95% CI 1.70–2.16), older age (WMDs = 6.89, 95% CI 3.10–10.67), having a smoking history (ORs =1.91, 95% CI 1.48–2.47), pulmonary comorbidities predicted (HRs = 2.08, 95% CI 1.89–2.30), longer RA duration (ORs = 1.03, 95% CI 1.01–1.05), older age of RA onset (WMDs =4.46, 95% CI 0.63–8.29), positive RF (HRs = 1.15, 95%CI 0.75-1.77; ORs = 2.11, 95%CI 1.65–2.68), positive ACPA (ORs = 2.11, 95%CI 1.65–2.68), higher ESR (ORs = 1.008, 95%CI 1.002–1.014), moderate and high DAS28 (≥3.2) (ORs = 1.87, 95%CI 1.36–2.58), rheumatoid nodules (ORs = 1.87, 95% CI 1.18-2.98), LEF use (ORs = 1.42, 95%CI 1.08–1.87) and steroid use (HRs= 1.70, 1.13–2.55). The use of biological agents was a protective factor (HRs = 0.77, 95% CI 0.69–0.87). Conclusion(s) The pooled prevalence of RA-ILD in our study was approximately 18.7%. Furthermore, we identified 13 risk factors for RA-ILD, including male sex, older age, having a smoking history, pulmonary comorbidities, older age of RA onset, longer RA duration, positive RF, positive ACPA, higher ESR, moderate and high DAS28 (≥3.2), rheumatoid nodules, LEF use and steroid use. Additionally, biological agents use was a protective factor.

Search for predictors of methotrexate toxicity in rheumatoid arthritis

Aim. To determine prognostic markers of methotrexate (MT) toxicity in rheumatoid arthritis (RA).Materials and methods. The study included 294 patients with RA who were prescribed MT at a dose of 10 to 25 mg per week for the first time as basic anti-inflammatory therapy (BPVT). The following adverse events (AEs) were recorded: hepatotoxicity, toxicity from the gastrointestinal tract, blood system. Qualitative parameters were considered as possible predictors of MT intolerance: gender, obesity, smoking, systemic manifestations, as well as rheumatoid factor (RF), antibodies to cyclic citrullinated peptide (ACCP), intake of glucocorticosteroids (GCS), form of administration of MT; and quantitative: age of RA onset, baseline disease activity according to DAS28 (Disease Activity Score 28) and HAQ (Health Assessment Questionnaire), MT dose. Statistical processing was performed by one-factor methods using Pearson’s χ2 test with Yates correction, Fisher’s exact two-tailed test, Mann–Whitney U-test, and Student’s t-test. Multivariate analysis was carried out by binary logistic regression.Results. In a univariate analysis, significant results were obtained for hepatotoxicity: a direct correlation with the use of corticosteroids at the onset (odds ratio (OR) 2.0; 95 % confidence interval (CI) 1.1–3.8, p = 0.03), inversely correlated with MT tablet intake (OR 0.5, 95 % CI 0.2–0.95, p = 0.03). According to the results of multivariate analysis, hepatotoxicity was recorded more often when taking GCS in the debut 2.01 times (95 % CI 1.02–3.96, p = 0.043), and in the presence of ACCP – 3.16 times (95 % CI 1.06–9.45, p = 0.039); and less frequently when taking tableted MT by 2.62 times (95 % CI 0.17–0.84, p = 0.017). Gastrointestinal toxicity tends to be associated with a younger age of RA onset (p = 0.06) and greater RA HAQ activity at onset (p = 0.07).Conclusions. Hepatotoxicity is more expected in patients seropositive for ACCP and GCS treatment in the onset of RA, but is less common when taking MT tablets. AEs from the gastrointestinal tract are associated with a younger age of onset of the disease and a greater degree of activity according to the HAQ index.

Association Study of Anticitrullinated Peptide Antibody Status with Clinical Manifestations and SNPs in Patients Affected with Rheumatoid Arthritis: A Pilot Study.

Introduction Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology that leads to disability due to articular and extra-articular damage. RA prevalence is variable. The disease is most common among females with a 3 : 1 ratio. The interaction of environmental and host factors contributes to RA development. Currently, the genome-wide association studies (GWAS) give the opportunity to uncover the RA genetic background. Anticitrullinated peptide antibody (ACPA) is a highly specific RA antibody, associated with poor prognosis and severe course of RA, and regulated by numerous genes. Our study is aimed at investigating whether there are any clinical and genetic aspects correlate with ACPA presence in Kazakhstani patients with RA. Indeed, the available studies on this subject are focused on Caucasian and East Asian populations (mainly Japanese and Chinese), and there are scarce data from Central Asia. Methods Our study included 70 RA patients. Patients' blood samples were collected and genotyped for 14 SNPs by real-time polymerase chain reaction (RT-PCR). General examination, anamnestic, and clinical and laboratory data collection were carried out. Statistical analysis was performed using R statistics. Results and Conclusion. Our study revealed a significant association of ACPA positivity with Fc receptor-like 3 (FCRL3) and ACPA negativity with signal transducer and activator of transcription 4 (STAT4) genes, but not with T cell activation Rho GTPase activating protein (TAGAP). In addition, ACPA positivity was associated with radiographic progression, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), age of RA onset, the patient global assessment, body mass index (BMI), and Gamma globulin. Conclusion Remained 11 earlier identified significantly associated in Caucasian and Asian population SNPs were not replicated in our cohort. Further studies on larger cohorts are needed to confirm our findings with higher confidence levels and stronger statistical power.

Risk Factors Associated with Aggravation of Cervical Spine Lesions in Patients with Rheumatoid Arthritis: A Retrospective Longitudinal Cohort Study.

A retrospective cohort study. To examine factors related to severe aggravation of preexisting cervical lesions in patients with rheumatoid arthritis (RA) under current pharmacologic treatments with biologics. Advanced RA cervical lesions carry a risk of irreversible damage to the spinal cord; however, risk factors for aggravation are unclear after the use of biologics became more popular. Of 166 patients with preexisting cervical lesions at baseline, 87 who had cervical X-ray images taken at baseline and at the final visit (with an interval of more than 1 yr) were evaluated retrospectively. Aggravated instabilities determined at the final visit, were defined as follows: atlantoaxial subluxation (AAS) = atlantodental interval ≧ 10 mm; vertebral subluxation (VS) = a Ranawat value < 10 mm; and subaxial subluxation (SAS) = an anterior vertebral slip ≧ 4 mm or a multilevel slip ≧ 2 mm. Patients were divided into two groups based on the radiographic results: severe aggravation and non-severe aggravation. Explanatory variables were gender, age of RA onset, duration of disease, average observation period, Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) at baseline, drug treatment history, presence of mutilating deformities in the hands, presence of RA-related joint surgery, and the prevalence of each cervical lesion at baseline. The severe group comprised 14 patients (16.1%). There was no significant difference between the two groups with respect to demographic data. Multivariate logistic regression analysis revealed that preexisting SAS lesions (odds ratio: 7.59, 95% confidence interval: 1.16-49.6) and no history of biologic treatment (odds ratio, 0.10; 95% confidence interval, 0.17-0.58) were associated with aggravation. Preexisting SAS lesions were associated with aggravation. Meanwhile, biologics may be effective at preventing aggravation.Level of Evidence: 3.

Should we reconsider the definition of elderly-onset rheumatoid arthritis in an ageing society?

The management of elderly-onset rheumatoid arthritis (EORA) is challenging due to progressive functional disability, increased comorbidities, and high drug-related risks. EORA is defined as disease onset after 60 years since 1985. We assessed whether this cut-off age was optimal in a progressively ageing society. This study used two cohorts of consecutive rheumatoid arthritis (RA) patients: the Nippon Medical School (NMS) cohort (n = 204) and the Keio cohort (n = 296). Clinical findings independently correlated with the age of RA onset were selected as 'EORA features' from previously reported EORA characteristics using univariable and multivariable regression analyses. Receiver operating characteristic curve analysis was conducted to determine the cut-off age that best selected patients with all EORA features. Acute onset, negative anti-cyclic citrullinated peptide antibody, and high erythrocyte sedimentation rate were selected as 'EORA features' in both cohorts. Patients with all EORA features were more numerous with age and almost exclusively older than 65years. The optimal EORA cut-off age was 73years with an area under the curve (AUC) of 0.82 in the NMS cohort and 68 with an AUC of 0.93 in the Keio cohort. In the NMS cohort, Health Assessment Questionnaire-Disability Index and comorbidities in patients with disease onset between 60years and the projected cut-off age were similar to those in younger-onset RA, but differed from those in patients with disease onset older than the projected cut-off age. The optimal EORA cut-off age was greater than the conventional definition, but this needs to be validated in different patient populations.

AB0164 THE EFFECT OF RHEUMATOID ARTHRITIS ON FEMALE FERTILITY

Background:Infertility is a disease of the reproductive system defined by the failure to achieve clinical pregnancy after 12 months or more of regular unprotected sexual intercourse. Although rheumatoid arthritis (RA) tends to have a late onset, the disease also occurs during child-bearing years and may interfere with procreation.Objectives:The aim of this study was to compare fertility rates in women with RA with birth-year-matched references from the general population.Methods:This is a case-control study. Menopausal married women who were diagnosed in the department of Rheumatology at Hedi Chaker Hospital before the age of forty were recruited into this study as cases and apparently healthy age matched married women were recruited as controls. Demographic, clinical, immunological, radiological and therapeutic data were collected from each case using the medical record of patient. Data obtained included age, age of RA onset, duration of RA, extra-articular manifestations, Rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (ACPA), the presence of erosions on radiographs of hands and feet and the therapy.Rheumatoid arthritis and controls women were asked to state their menstrual regularity, age at menarche, age at menopause, gestity, parity, number of living children, time to first pregnancy, presence of primary or secondary infertility, the interpregnancy interval, presence of miscarriage or in utero foetal death (IUFD) or preterm delivery and their number.Results:The mean ages of the cases and controls was 54 ± 8,11 years [39, 69]. The median duration since onset of RA in the patients was 22,5 ± 10,53 years [1, 47]. The mean age of onset of the disease was 31,4 ± 6,3 [18, 39] years. Forty-nine percent (49%) of patient had extra-articular manifestations: ocular sicca syndrome in 43,8% of cases, pulmonary fibrosis in 5,3% of cases and rheumatoid nodules in 1,8 % of cases. Rheumatoid factor (RF) was present in 61,4% of cases while anti-CCP anti-body was present in 59,6% of cases.Erosive polyarthritis was found in 80,7% of patients. The mean rate of RF was 319,7 ± 462,4 UI/ml and the mean rate of anti-CCP was 185,8 ± 264.Women with RA had a statistically significant mean time to pregnancy longer than the control group. Primary infertility was seen in 15 (26,3%) patients and 2 (3,5%) controls, whereas secondary infertility was seen in 31 (54,5%) patients and 2 (3,5 %) controls. The patients were significantly more likely to have primary and secondary infertility. There were no significant differences in the age at menarche, the number of children, the gestity and the parity between the two groups. The age at menopause was statistically significant lower in the group patients than controls.Conclusion:Our study showed that RA women are more likely to have reduced fertility than general population. Although this study cannot definitively address the issue of impaired fertility among women with RA, the results are suggestive enough to warrant further research into the link between RA and fertility that takes women’s childbearing choices into account.

Risk factors associated with cervical spine lesions in patients with rheumatoid arthritis: an observational study

BackgroundFew reports have described the association between rheumatoid arthritis (RA) cervical lesions and osteoporosis, especially in patients with vertical subluxation (VS) that could be induced by the collapse of lateral masses in the upper cervical spine. Therefore, this study aimed to investigate the prevalence and risk factors for cervical lesions in patients with RA under current pharmacological treatments with biological agents, and to investigate the relationship between osteoporosis and VS development.Methods One hundred eighty-five consecutive patients with RA who underwent both cervical plain radiography and bone mineral density (BMD) scanning were enrolled. RA cervical lesions included atlantoaxial subluxation (AAS), VS, and subaxial subluxation (SAS). We assigned patients with AAS, VS, or SAS to the cervical-lesion group, and all other patients to the non-cervical-lesion group. Radiological findings, BMD, and clinical data on RA were collected. We used multivariate logistic regression analyses to assess the risk factors for cervical lesions in patients with RA.ResultsThe cervical-lesion and non-cervical-lesion groups included 106 and 79 patients, respectively. There were 79 patients with AAS, 31 with VS, and 41 with SAS. The cervical-lesion group had a younger age of RA onset, longer RA disease duration, higher RA stage, and lower femoral neck BMD than the non-cervical-lesion group. Multivariate analyses showed that the risk factors for RA cervical lesions were prednisolone usage, biological agent usage, and higher RA stage. Prednisolone usage and femoral neck BMD were the risk factors for VS.ConclusionsCervical lesions were confirmed in 57 % of the patients. Prednisolone usage, biological agent usage, and higher RA stage were significant risk factors for cervical lesions in patients with RA. The general status of osteoporosis might contribute to the development of VS.

Red meat intake is associated with early onset of rheumatoid arthritis: a cross-sectional study

Accumulating evidence has implicated dietary factors as important risks for rheumatoid arthritis (RA) development, but analyses of the effects of red meat consumption on RA have yielded diverging results. The aim of this study was to explore the association between red meat and RA in a large-scale, cross-sectional study. From June to December 2016, a total of 733 patients were investigated, from which 707 participants were included in the analysis. These patients were divided into two groups according to their consumption of red meat (< 100 g/day; ≥ 100 g/day). The intake of red meat was assessed via physician-administered questionnaire. Generalized linear models were used to analyze relationships between the red meat intake and RA, adjusting for potential confounders including demographic, clinical, laboratory, and other dietary factors. Compared with low-intake red meat RA patients, high-intake red meat patients had an earlier onset age (p = 0.02) and had higher BMI (p = 0.003). The age at disease onset for the high-intake patients was 6.46 years earlier than for low-intake patients, after adjustment for demographic and other possible confounders (β = − 6.46, 95% CI − 9.77, − 3.15; p = 0.0001). Further, stratified analyses showed that this inverse association of red meat intake with RA onset age was especially evident in smokers and overweight patients (BMI ≥ 24 kg/m2). In conclusion, high-intake red meat is associated with early onset of RA, especially in smokers or overweight patients. The findings indicate that eating less red meat could be a recommendation given to patients at risk for RA development.

Excess mortality persists in patients with rheumatoid arthritis.

To investigate the causes and risk of death in a large cohort of Korean patients with rheumatoid arthritis (RA). Patients in the Hanyang BAE (Bae registry of Autoimmune diseases for Epidemiology) RA cohort who fulfilled the American College of Rheumatology criteria were analyzed. A total of 2355 patients were enrolled from October 2001 to December 2015. Mortality data were derived by linking with data from the Korean National Statistical Office. Standardized mortality ratio was estimated by dividing observed deaths by expected number of deaths in the general population. Over the observation period, 225 deaths were reported. Total age- and sex-adjusted standardized mortality ratio was 1.65 (95% confidence interval 1.44-1.87). The most common cause of death was malignancy (40 cases; 17.8%), followed by respiratory disease (38 cases; 16.9%) and cardiovascular disease (32 cases; 14.2%). Mortality rate and causes of death differed according to year and age of RA onset. Compared with survivors, individuals who died were more likely to be male, smokers, diagnosed with RA at an older age, and to have long disease duration, higher erythrocyte sedimentation rate and C-reactive protein, higher rheumatoid factor positivity rate, more severe radiographic damage, and more comorbidities. The mortality rate of patients with RA remains higher than that of the general population. Therefore, to improve the survival of patients with RA, attention should be paid to the management of comorbidities as well as to the RA itself.

High-resolution computed tomography of the lung in patients with rheumatoid arthritis

An international consensus for rheumatoid arthritis (RA) patients at risk of developing interstitial lung disease (ILD) is still lacking. The aims of study were to evaluate: the prevalence of ILD involvement in RA over high-resolution computed tomography (HRCT); the relationships between pulmonary function tests (PFTs), patient-centered measurements, and ILD; and the potential risk factors contributing to RA-ILD patients.Data regarding the clinical characteristics (age, sex, age at onset of RA), laboratory findings (rheumatoid factor [RF] and anti-citrullinated protein antibodies [ACPA]), respiratory functional assessment (forced vital capacity [FVC] and carbon monoxide diffusion capacity [DLCO]), patient-centred measures of dyspnea (PCMD), Health Assessment Questionnaire—Disability Index (HAQ-DI), and HRCT have collected retrospectively. HRCT abnormalities were evaluated using a conventional visual reader-based score (CoVR) and a computer-aided method (CaM). The relationships between the 2 HRCT scores—PFTs and PCMD—were calculated using Pearson correlation. The area under the receiving-operating characteristic (AUC-ROC) curve was calculated to determine the discriminatory performance of measurements between patients with and without ILD. The multivariate regression model was used to evaluate the association force between ILD and RA characteristics.In all, 151 patients (45 males and 106 females, mean age 53.4 ± 7.6 years) were included. ILD had been detected in 29 patients out of 151 (19.2%). Usual interstitial pneumonia was the most common HRCT. RA-ILD patients were older, and older at RA onset (both P < .01), with a higher HAQ-DI (P < .05) than patients without ILD. ACPA positivity and titer were higher in the RA-ILD group (P = .02). Extent and severity of ILD, and total CoVR and CaM score closely related to DLCO and PCMD (both P < .0001). A reduced DLCO was the most sensitive test for predicting the presence of ILD on HRCT (AUC-ROC 0.811 ± 0.037). Advanced age (P < .0001), age at RA onset (P = .025), ACPA titer (P = .004), and smoking (P = .008) were independent explanatory variables of HRCT damage in multivariate analysis.The RA-ILD is associated with age and older age of RA onset, smoking, and ACPA titer. DLCO seems to be the most sensitive parameter to predict ILD on HRCT, followed by PCMD.

Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts

ObjectivesTo assess predictive factors for rheumatoid arthritis interstitial lung disease (RA-ILD) in two early rheumatoid arthritis (RA) inception cohorts with a focus on methotrexate (MTX) exposure.DesignMulticentre prospective early RA inception...

Occurrence of anti-CCP2 and RF isotypes and their relation to age and disease severity among Sudanese patients with rheumatoid arthritis

ObjectiveAnti-cyclic citrullinated peptide 2 antibodies (anti-CCP2) and rheumatoid factor (RF) in rheumatoid arthritis (RA) has been extensively assessed in industrialized countries. We investigated the diagnostic and prognostic impact of anti-CCP2 and RF isotypes in a Sudanese cross-sectional RA cohort.MethodsConsecutive RA patients (n = 281) diagnosed according to the 1987 ACR criteria were included 2008–2010. Anti-CCP2 and RF isotypes (IgA, IgM, and IgG) were measured by enzyme immunoassay in 262 patients, with reference intervals aligned to the same diagnostic specificity as for anti-CCP2 (97.6%) using national controls.ResultsIgA RF was the predominant RA-associated autoantibody (56%), followed by IgM RF and anti-CCP2 (both 52%) and IgG RF (49%). In receiver operator characteristic analysis, IgA RF also showed the largest area under the curve. Patients with IgG RF were younger and had 8 years lower median age of disease onset compared to antibody negative patients (p < 0.0001). IgG RF was the only marker associated with a high number of involved joints (p = 0.028), and together with anti-CCP2 were the strongest markers for finger deformities (p = 0.016 and p = 0.012), respectively. No statistical differences were found for disease duration, ESR and Hb levels, and occurrence of erosions/osteopenia for any of the investigated autoantibodies.ConclusionWhereas IgA RF showed the best diagnostic performance, IgG RF associated with low age of RA onset, high number of involved joints, and finger deformities. These findings indicate that RA-associated antibodies other than conventional IgM RF and anti-CCP2 might be informative in non-Caucasian RA populations.

IL1F7 Gene Polymorphism Is not Associated with Rheumatoid Arthritis Susceptibility in the Northern Chinese Han Population: A Case-Control Study.

Background:Interleukin (IL)-37, also called IL1F7, is a natural inhibitor of inflammatory and immune responses. It is involved in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the role of IL1F7 gene polymorphism in RA susceptibility in a large cohort of patients.Methods:Five selected single-nucleotide polymorphisms in IL1F7 genes (rs2723186, rs3811046, rs4241122, rs4364030, and rs4392270) were genotyped by TaqMan Allelic Discrimination in Northern Chinese Han population. The allele and the genotype were compared between patients with RA and healthy controls. Association analyses were performed on the entire data set and on different RA subsets based on the status of the anti-cyclic citrullinated peptide antibody and the rheumatoid factor by logistic regression, adjusting for age and gender.Results:Trend associations were detected between rs2723186, rs4241122, rs4392270, and RA in Stage I (160 patients with RA; 252 healthy controls). Further validation in Stage II comprised 730 unrelated patients with RA (mean age: 54.9 ± 12.6 years; 81.6% females) and 778 unrelated healthy individuals (mean age: 53.5 ± 15.7 years; 79.5% females). No significant differences in the distributions of alleles and genotypes were observed between the case and control groups in both the entire set and the different RA subsets. Disease activity and age of RA onset were also not associated with genotype distributions.Conclusion:IL1F7 gene polymorphism does not significantly influence RA susceptibility in the Northern Chinese Han population.

Relationship of epigenetic variability of miR-124 to extracellular matrix remodelling and age-related MMP-3 expression in rheumatoid arthritis

The aim of study was to examine relation among miR-124 and serum levels of selected cytokines and chemokines, MMP-3, production of auto-antibodies, and factors describing clinical activity (DAS28) and radiographic progression in rheumatoid arthritis (RA). A total of 80 RA patients according to the ACR classification criteria, and 32 control subjects were recruited into study. The measurements of miR-124 and U-6 expression, CRP, anti-CCP, rheumatoid factors (RFs), radiographs of both hands with calculation of total sharp score (TSS), DAS28 and cytokines, chemokines and MMP levels in serum were obtained from all RA patients. miR-124 was down-regulated in RA patients compared to controls (7-fold decrease). The miR-124 expression correlated to MMP-3 levels (p < 0.001), which were in multivariate analysis associated to age of RA onset. Higher levels were detected in younger subjects. No relation of miR-124 expression to measures of RA activity (DAS28 score; TSS), auto-antibodies (anti-CCP, RF, RF IgG, RF IgA, RF IgM), acute inflammatory markers (CRP, IL-6), and other cytokine and chemokines (IL-13, IL-15, IL-8, TNF-α, MCP-1, RANTES) was observed. In conclusion, we present a down-regulation of miR-124 in RA patients and its correlation to MMP-3 levels, which associated to age of RA onset.

Discontinuation of Biologic Therapy in Rheumatoid Arthritis: Analysis from the Corrona RA Registry.

IntroductionDespite the availability of multiple effective therapies, discontinuation/switching of treatment is common for many patients with rheumatoid arthritis (RA). This study was designed to examine initiation of biologic disease-modifying anti-rheumatic drugs (bDMARDs) within the Consortium of Rheumatology Researchers of North America (Corrona) RA Registry, and characterize reasons for discontinuation.MethodsInclusion criteria were: Corrona-registered adults (≥18 years) with RA (2002–2011); age of RA onset: ≥16 years; ≥6 months’ follow-up after initiation of first/subsequent bDMARD. Patients receiving both tumor necrosis factor antagonists and non-TNF antagonists were included. Treatment discontinuation was defined as first report of stopping initial therapy or initiation of new bDMARD at/between visits, using a follow-up physician questionnaire.ResultsOverall, 6209 patients met inclusion criteria and 80.7% received TNF antagonists. Median time to discontinuation/change of therapy was 25.1 months (26.5 months with TNF antagonists vs. 20.5 months with non-TNF antagonists; log-rank p < 0.0001); 82.2, 67.3, and 51.1% of patients remained on therapy at 6, 12, and 24 months, respectively. Reasons for discontinuation were captured for 49.2% of patients, including: loss of efficacy (35.8%); physician preference (27.8%); safety (20.1%); patient preference (17.9%); and no access to treatment (9.0%). Baseline factors with greatest correlation to discontinuation were modified Health Assessment Questionnaire scores, patient-reported anxiety/depression, initiation of bDMARD treatment in 2007–2010 versus 2002–2003, and Clinical Disease Activity Index scores.ConclusionsAlmost one-third of patients in the US discontinue currently available bDMARD therapies for RA by 12 months and almost half by 24 months, most commonly due to loss of efficacy.FundingCorrona LLC and MedImmune.

Latitude gradient influences the age of onset of rheumatoid arthritis: a worldwide survey.

The age of onset of rheumatoid arthritis (RA) is an important outcome predictor. Northern countries report an age of RA onset of around 50years, but apparently, variability exists across different geographical regions. The objective of the present study is to assess whether the age of onset of RA varies across latitudes worldwide. In a proof-of-concept cross-sectional worldwide survey, rheumatologists from preselected cities interviewed 20 consecutive RA patients regarding the date of RA onset (RAO, when the patient first noted a swollen joint). Other studied variables included location of each city, rheumatologist settings, latitudes (10° increments, south to north), longitudes (three regions), intracountry consistency, and countries' Inequality-adjusted Human Development Index (IHDI). Data from 2481 patients (82% females) were obtained from 126 rheumatologists in 77 cities of 41 countries. Worldwide mean age of RAO was 44±14years (95% CI 44-45). In 28% of patients, RA began before age 36years and before age 46years in 50% of patients. RAO was 8years earlier around the Tropic of Cancer when compared with northern latitudes (p<0.001, 95% CI 3.5-13). Multivariate analysis showed that females, western cities, and latitudes around the Tropic of Cancer are associated with younger age of RAO (R 2 0.045, p<0.001). A positive correlation was found between the age of RAO and IHDI (r=0.7, p<0.01, R 2 0.5). RA often begins at an early age and onset varies across latitudes worldwide. We postulate that countries' developmental status and their geographical and geomagnetic location influence the age of RAO.

Increased healthcare resource utilization in higher disease activity levels in initiators of TNF inhibitors among US rheumatoid arthritis patients

Objective: Determine healthcare resource utilization (HCRU) in biologic-naïve initiators of TNF inhibitors (TNFis) associated with their disease activity from a national cohort of rheumatoid arthritis (RA) patients.Methods: RA patients were identified at their first TNFi initiation (index date) in the Corrona registry. Patients with age of RA onset <18, comorbid psoriasis/psoriatic arthritis, fibromyalgia, or osteoarthritis were excluded. Patients were categorized into disease activity (DA) strata by the lowest level of DA (and sustaining low levels for at least two visits) using the Clinical Disease Activity Index (CDAI) across all visits in Corrona while on a TNFi during 1 year after initiation. Rates of all-cause and RA-related hospitalizations, rheumatologist visits, and joint surgeries while on TNFi therapy were reported and compared across DA levels along with the incidence rate ratio (IRR) adjusted for age, gender, and RA duration using Poisson mixed models.Results: Of 1931 RA patients: 15% achieved sustained remission, 22% remission, 14% sustained low DA, 23% low DA and 27% moderate/high DA (M/HDA). Those in M/HDA had statistically higher rates of hospitalizations (37.3 per 100 patient years (py), 95% CI: 31.6–43.7 and joint surgeries (20.8 per 100 py, 95% CI: 16.6–25.8) compared to the sustained remission cohort, resulting in respective IRRs of 2.3 (p < 0.001) and 1.7 (p = 0.046).Conclusion: Many biologic naïve RA patients initiating TNFi failed to achieve sustained remission during a 1 year period while remaining on TNFi therapy. Patients in higher DA levels had higher HCRU rates vs. patients in sustained remission, suggesting that achieving treat-to-target goals would reduce health care expenses.

Autoimmune Thyroiditis In A Population With Rheumatoid Arthritis

Abstract Introduction: Autoimmune thyroiditis (AIT) associates a multitude of osteoarticular and muscular complaints but, in the same time, the association between AIT and rheumatoid arthritis (RA) remains a matter of controversy. Material, patients and method: We performed a retrospective cross-sectional study over 69 patients with RA admitted successively in the the IInd Medical Clinic of Railway Hospital between 01 Jan 2015 and 01 Aug.2015, subdivided into two groups: with and without AIT. A number of parameters were studied in each group: age, environment, parity and number of gestations, smoker status, education level, medium duration of disease, presence of rheumatoid factor (RF), of anti-cyclic citrullinated protein antibodies (ACPA), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, treatment for RA, VAS score, DAS 28 score. Conclusions: The percentage of patients with RA and AIT is 17.391%, higher than in general population, and so we consider that screening for AIT in patients with RA should be done. Patients with RA and AIT have a younger age of RA onset, belong to the urban environment and have a higher level of education than the ones with RA but without AIT. No correlation between the occurrence of AIT and the presence of ACPA was found.

Association of complement factor B allotypes and serum biomarkers inrheumatoid arthritis patients and their relatives.

The aim of the study was to investigate the allotypic variability of complement factor B (BF) in patients and relatives with rheumatoid arthritis (RA) and its association with serological biomarkers and clinical features of the disease. BF allotypes were determined by high-voltage agarose gel electrophoresis in serum samples of 180 patients with RA, 198 relatives and 98 controls from Southern Brazil. Anticyclic citrullinated peptide (anti-CCP), antimutated citrullinated vimentin (anti-MCV) and IgA-rheumatoid factor (RF) were determined by ELISA and IgM-RF by latex agglutination in all samples. No significant differences were found in the allotypic variants of BF between patients with RA, relatives and controls, nor associations with gender and age of RA onset. BF*S07 allotype was significantly associated with extra-articular manifestations (EAMs; Secondary Sjögren Syndrome, pneumonitis, rheumatoid nodules) in patients with RA (P=0.02; OR=6.62). Patients with phenotype BF F had lower positivity for anti-MCV biomarker (P=0.02; OR=0.22) and those with allotype BF*S had higher prevalence of this autoantibody (P=0.02; OR=3.77). An increased frequency of RF-IgA was detected in relatives of patients with RA with BF FS07 phenotype (P=0.02; OR=7.78). Complement BF variability did not influence the development of RA in the studied patients, but BF variants may act as markers of disease prognosis, such as development of EAMs, corroborating with the role of the alternative pathway in the pathogenesis of RA.

Relationship Between Physical Disability, Disease Activity and Osteoporosis in Patients With Rheumatoid Arthritis

Objectives: This study aims to assess the relationship between the physical disability, degree of disease activity, and bone mineral density in menopause patients diagnosed with rheumatoid arthritis (RA). Patients and methods: The study included 130 females (mean age 62.77±7.51 years; range 57 to 69 years) who reached menopause, and were diagnosed with RA. Bone mineral density was measured at the lumbar spine level and femur (femur head, entire femur) through osteodensitometry with dual X-ray absorptiometry. Age, weight, height, body mass index, environment (urban, rural), age of the menarche and the onset of menopause, duration of menopause, smoker/non-smoker status, RA stage, RA onset age, duration of RA, extra-articular manifestations, the presence of rheumatoid factor, erythrocyte sedimentation rate, C reactive protein, disease activity score 28, and physical disability quantified by modified health assessment questionnaire were used for evaluating the RA activity. Results: The mean body mass index was 27.74±4.37 kg/m 2 , the mean duration of menopause was 16.42±8.15 years. About 44.62% of the patients had osteoporosis. Osteoporosis frequency increased with RA stage: 23.81% in stage II, 55.0% in stage III, and 77.78% in stage IV. About 58% of the patients received prednisone treatment. Independent risk factors for osteoporosis were: age, environment, body mass index, duration of menopause, rheumatoid factor presence and extra-articular manifestations, duration of RA, modified health assessment questionnaire, erythrocyte sedimentation rate and C reactive protein. Conclusion: Physical disability and disease activity contribute to the occurrence of osteoporosis in patients diagnosed with RA.