Cohort Of Rheumatoid Arthritis Patients Research Articles

Perioperative Use of Methotrexate and Tumor Necrosis Factor α Inhibitors Combination Therapy Is Not Likely to Increase Post-Operative Infection Rate in the National Veterans Health Administration Administrative Databases

Objective: The aim of the study is to assess the risk of post-operative outcome in rheumatoid arthritis (RA) patients continuing versus stopping combination therapy of methotrexate (MTX) and hydroxychloroquine (HCQ) or tumor necrosis factor α inhibitors (TNF) prior to surgery. Methods: Using the United States Veterans Affairs (VA) databases, we identified surgical procedures in a 17-year cohort of RA patients. Among those patients, those on MTX + HCQ or MTX + TNF were identified. Post-operative outcome variables include infection, length of post-operative hospital stay and death. Results: We identified a total of 29,708 surgeries in RA patients. Among them, we identified the most recent elective surgeries without pre-operative infection in 16,174 patients. There were 783 and 550 patients on MTX + HCQ and MTX + TNF, respectively. The rates of post-op infection were 5% and 4% for the MTX + HCQ and MTX + TNF continuing medication groups, respectively, similar to the general RA population (5%). Sensitivity analyses at various time points of discontinuation combination therapies prior to surgery did not show significant change in terms of infection. Conclusions: The prevalence of adverse outcome is low. The proportion of post-operative infection in continuing and discontinuing medicine groups is similar for both MTX + HCQ and MTX + TNF. While we were unable to formally compare proportions of post-operative infection among the two groups, these preliminary findings do not support the hypothesis that continuing either MTX + TNF or MTX + HCQ combination during perioperative period increases post-operative infection compared with discontinuation prior to therapy.

Crosstalk between tumor necrosis factor-alpha signaling and aryl hydrocarbon receptor signaling in nuclear factor –kappa B activation: A possible molecular mechanism underlying the reduced efficacy of TNF-inhibitors in rheumatoid arthritis by smoking

ObjectivesTo examine the influence of smoking on biologics treatment against different therapeutic targets, such as TNFα, IL-6, and T cell, in rheumatoid arthritis (RA) and elucidate the underlying molecular mechanism. MethodsThe association between drug-discontinuation due to poor therapeutic response and smoking status was analyzed individually in biologics against different therapeutic targets by a multivariable logistic regression analysis using the “NinJa” Registry, one of the largest cohorts of Japanese RA patients. In vitro enhancement of TNFα-induced NF-κB activation and subsequent proinflammatory cytokine production by cigarette chemical components was examined by RT-PCR, qPCR, ELISA, and western blotting using an immortalized rheumatoid synovial cell line, MH7A. ResultsThe rate of drug-discontinuation due to poor therapeutic response was higher in the current smoking group than in the never- or ever-smoking groups (the odds ratio of current/never smoking: 2.189, 95%CI; 1.305–3.672,P = 0.003; current/ever: 1.580, 95%CI; 0.879–2.839,P = 0.126) in the TNF inhibitor (TNFi) treatment group. However, this tendency was not observed in either the IL-6 or T cell inhibitor treatment groups. Cigarette smoke chemical components, such as benzo[α]pyrene, known as aryl hydrocarbon receptor (AhR) ligands, themselves activated NF-κB and induced proinflammatory cytokines, IL-1β and IL-6. Furthermore, they also significantly enhanced TNFα-induced NF-κB activation and proinflammatory cytokine production. This enhancement was dominantly inhibited by Bay 11-7082, an NF-κB inhibitor. ConclusionsThese results suggest a crosstalk between TNFα signaling and AhR signaling in NF-κB activation which may constitute one of the molecular mechanisms underlying the higher incidence of drug-discontinuation in RA patients undergoing TNFi treatment with smoking habits.

Association of galectin-3 with markers of myocardial function, atherosclerosis, and vascular fibrosis in patients with rheumatoid arthritis.

Galectin-3 has emerged as a promising novel biomarker of cardiovascular fibrosis in patients with cardiovascular diseases. We investigated whether galectin-3 correlates with markers of vascular fibrosis, subclinical atherosclerosis, and cardiac function in patients with rheumatoid arthritis (RA), a disease accompanied by high cardiovascular risk. RA and non-RA individuals underwent applanation tonometry, carotid ultrasound, and impedance cardiography, to obtain markers of arterial stiffness, subclinical atherosclerosis, and myocardial function, respectively. Cardiovascular risk was estimated from the Framingham Heart Study. Serum levels of galectin-3 were determined by enzyme-linked immunosorbent assay. Galectin-3 was elevated in RA patients (n = 85) compared to controls (n = 39), but this difference was no longer significant after adjustment for the presence of cardiovascular comorbidities. In the univariate analysis, galectin-3 significantly correlated with markers of vascular stiffness (including pulse wave velocity, central blood pressure, central and peripheral pulse pressure, and total arterial compliance); atherosclerosis (carotid intima-media thickness); myocardial blood flow (cardiac output, stroke volume) and contractibility (acceleration and velocity index); systemic vascular resistance, and estimated cardiovascular risk. Multivariate analysis models revealed an independent association between galectin-3 and both cardiac output (β = -0.274, P = 0.039), as well as systemic vascular resistance (β = 0.266, P = 0.039). In a relatively well-controlled cohort of RA patients with low-grade systemic inflammation and long-standing disease, serum galectin-3 might be useful as a marker of cardiac function and cardiovascular fibrosis.

Prognostic Factors for Sustained Remission in a "Real Life" Cohort of Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) is the most frequent chronic polyarthritis. The current goal of RA treatment is to achieve clinical remission. The goal of this study was to determine the prevalence of remission in a cohort of patients from clinical practice, and to identify potentially modifiable factors associated with remission. A retrospective study was performed on a cohort of RA patients seen at the first consultation at the HUGC Rheumatology Service Dr. Negrín (HUGCDN) between first of January 2000 and thirtieth of April 2014. Sustained remission was defined as DAS28 less than 2.6 in the last two available visits in the medical history. A total of 463 patients were consecutively included, most (75%) women, with a mean age at the onset of RA of 50 years and a mean duration of the disease at follow-up of 8 years. 46% of the patients achieved sustained remission. Multiple logistic regression analyses found male sex (P=.031, OR 1.7, 95% CI 1.05-2.82), diagnosis in the first year of symptoms (P=.023, OR 1.7, 95% CI 1.07-2.69) and the initial DAS28 (P=.035) to be independent predictors for sustained remission. The 46% of the patients with RA followed in the HUGC Dr. Negrín are in persistent remission, being the early diagnosis a modifiable factor predictor of remission. Thus, an objective of the Rheumatology Service should be to improve the diagnostic delay of RA in the health area.

Common atherosclerosis genetic risk factors and subclinical atherosclerosis in rheumatoid arthritis: the relevance of disease duration

Rheumatoid arthritis (RA) is a common systemic autoimmune disease characterized by increased cardiovascular morbidity. Several previous studies assessed associations between common atherosclerotic genetic risk factors and subclinical atherosclerosis (SA) in RA patients, yet most of them gave negative results. We undertook a cross-sectional study to evaluate the association between previously reported SNPs and subclinical atherosclerosis in a cohort of Polish RA patients. 29 SNPs associated with atherosclerosis in general population were genotyped in 289 RA patients: 116 patients with SA (increased carotid intima–media thickness and/or presence of carotid plaque) and 173 patients without SA. To assess the cumulative effect of SNPs we calculated 3 weighted genetic risk scores: GRSIMT, GRSCP and GRSCAD, comprising intima–media thickness-associated SNPs, carotid plaque-associated SNPs and coronary artery disease-associated SNPs, respectively. None of the SNPs showed a significant association with SA. However, we found an association between SA and GRSIMT. Interestingly, this association was limited to patients with short disease duration (P = 0.00004 vs. P > 0.5, for comparison of GRSIMT among patients within the 1st quartile of disease duration vs. others, respectively). Patients within the 1st quartile of disease duration were more frequently disease modifying anti-rheumatic drugs (DMARDs)-naïve and less frequently treated with biologics. Our study suggests that in patients with early RA subclinical atherosclerosis may be driven by similar genetic factors as in general population, while in long-lasting disease, the role common genetic risk factors may decrease. Possibly, this effect may be due to the influence of DMARDs.

Early referral and control of disease\u2019s flares prevent Orthopedic and Hand Surgery Indication (OHSI) in a dynamic cohort of Hispanic early rheumatoid arthritis patients

BackgroundReconstructive joint surgery is an indicator of poor prognosis in rheumatoid arthritis (RA). Objectives of this study were to describe the incidence rate of orthopedic and hand surgery indication (OHSI) in an ongoing cohort of Hispanic early RA patients treated according to a T2T strategy and to investigate predictors.MethodsThrough February 2018, the cohort comprised 185 patients recruited from 2004 onwards, with variable follow-up, and rheumatic assessments at fixed intervals that included prospective determination of OHSI. Charts were reviewed by a single data abstractor. OHSI incidence rate was calculated. A case-control study nested within a cohort investigated the predictors; cases (OHSI patients) were paired with controls (1:4) according to age, sex and autoantibodies. A logistic regression model included baseline and cumulative (up to OHSI or equivalent) variables related to disease activity, treatment and to persistence with therapy. The IRB approved the study.ResultsPatients from the cohort were predominantly middle-aged (mean ± SD age: 38.5 ± 12.9 years) females (87.6%) with 5.4 ± 2.6 months of disease duration. The cohort contributed to 1538 patient-years of follow-up. Twelve patients received incidental OHSI at a follow-up of 85 ± 44.5 months. The OHSI incident global rate was 8/1000 patient-years. Longer symptom duration at cohort referral (OR: 1.313, 95%CI: 1.02–1.68, p = 0.032) and a higher number of flares/patient (OR: 1.608, 95%CI: 1.05–1.61, p = 0.015) predicted OHSI. OHSI patients had more severe flares than their counterparts, and the opposite figure was true for mild flares.ConclusionEarly referral for appropriate management and flare control may prevent OHSI in Hispanic recent-onset RA patients.

Lipids and Atherogenic Indices Fluctuation in Rheumatoid Arthritis Patients on Long-Term Tocilizumab Treatment.

Rheumatoid arthritis (RA) patients are at high risk of cardiovascular (CV) events, and the chronic inflammatory state may generate quantitative and qualitative changes in lipoprotein fractions. The anti-IL-6 receptor tocilizumab (TCZ), even if effective in inflammation and joint damage prevention, determined significant alterations to RA patients' lipid levels in randomized controlled trials, but real-world data are lacking. We evaluated the changes in lipid fraction levels and disease activity in a longitudinal cohort of RA patients on long-term treatment with tocilizumab (TCZ) in a community setting. We retrospectively selected 40 naïve-biologic RA patients on treatment with intravenous TCZ compared to 20 RA patients on methotrexate treatment as the control group. Total cholesterol (Tot-Chol), low-density lipoproteins (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured at the baseline and at 12, 24, and 52 weeks thereafter. At the same points, 28-joint disease activity score (DAS28), clinical disease activity index (CDAI), and EULAR clinical responses were also assessed. During the first 24 weeks, we observed in TCZ-treated patients a progressive statistically significant (p < 0.001) increase in Tot-Chol, LDL, HDL, and TG, which returned close to the baseline at 52 weeks. But no changes in the lipid-related CV risk indices Tot-Chol/HDL and LDL/HDL ratios and the atherogenic index (log10 TG/HDL) were detectable. Notably, we observed a statistically significant negative correlation between changes in lipid fractions and DAS28 or CDAI. The prolonged treatment with TCZ was associated to a transient increase in cholesterol's fractions during the first 6 months of treatment, with inverse correlation to disease activity, but with no impact on surrogate lipid indices of atherogenic risk. These findings may aid clinicians in interpreting the RA patient's lipid profile in daily clinical practice.

Evaluation of a Methodologic Approach to Define an Inception Cohort of Rheumatoid Arthritis Patients Using Administrative Data.

Identifying incident rheumatoid arthritis (RA) is desirable in order to create inception cohorts. We evaluated an approach to identify incident RA in health plan claims data. Both Medicare and commercial claims data were linked to Corrona, a US RA registry. We evaluated the accuracy of year of RA onset in the registry (gold standard) versus different claims algorithms, varying International Classification of Diseases, Ninth Revision codes for RA/arthritis, duration of health plan enrollment preceding diagnosis (minimum of 1 versus 2 years), and use of RA medications. Results were reported as positive predictive values (PPVs) of the claims-based algorithm for incident RA. Depending on the algorithm tested and whether patients were enrolled in Medicare or the commercial health plan, the PPVs for incident RA ranged from 68-81%. A 2-year clean period free of all RA-related diagnoses and medications was somewhat more optimal although, by comparison, a 1-year clean period yielded similar PPVs and retained approximately 90% more RA patients for analysis. Claims-based algorithms can accurately identify incident RA.

Association between anti-citrullinated alpha enolase antibodies and clinical features in a cohort of patients with rheumatoid arthritis: a pilot study.

In recent years several antibodies against citrullinated peptides (ACPAs) have been identified in patients with rheumatoid arthritis (RA) and their pathogenic, diagnostic and prognostic significance is under intense investigation. Among ACPAs, those targeting citrullinated alpha enolase (anti-CEP1) have been identified in RA but data about their ability to predict the development of erosive disease are conflicting. Furthermore, no data are currently available concerning their possible association with extra-articular manifestations (EAMs) in RA. The aim of this study was to investigate the prevalence and significance of anti-CEP1 from a prognostic point of view. In this pilot study we confirmed that anti-CEP1 Abs are associated with higher prevalence of bone erosions, but we also provided the first evidence of an association between anti-CEP1 Abs and RA interstitial lung disease (ILD). These results provide the basis to investigate the association between anti-CEP1 Abs and EAMs in larger cohorts of RA patients to possibly confirm its role as biomarker for RA-ILD.

Comparison of Serological Biomarkers in Rheumatoid Arthritis and Their Combination to Improve Diagnostic Performance.

The diagnosis of rheumatoid arthritis (RA) is based on a combined approach that includes serological markers such as rheumatoid factor (RF) and anti-citrullinated peptide/protein antibodies (ACPA). The goal of this study was to evaluate the clinical performance of several RF and ACPA immunoassays for the diagnosis of RA, as well as the diagnostic value of a combinatory approach with these markers. The study cohort included 1,655 patients from the Swiss Clinical Quality Management registry with sera from 968 patients with RA and 687 disease controls, including patients with axial spondyloarthritis (n = 450) and psoriatic arthritis (n = 237). ACPA were determined by anti-CCP2 IgG enzyme-linked immunosorbent assay (ELISA), QUANTA Flash® CCP3 IgG [chemiluminescent immunoassay (CIA)], and QUANTA Lite® CCP3 IgG ELISA. RF was determined by ELISA (QUANTA Lite® RF IgM, RF IgA, and RF IgG) and with two research use only CIAs (QUANTA Flash® RF IgM and RF IgA). All three ACPA assays showed good discrimination between RA patients and controls and good clinical performance. Overall, CCP3 performed better than CCP2. More pronounced differences were observed between the RF assays. We observed that CIA platforms for both RF IgM and RF IgA showed better performance than the ELISA platforms. Excellent and good total agreements were found between ELISA and CIA for CCP3 (total agreement 95.3%, kappa = 0.90), and between CCP2 and CCP3 ELISA (total agreement 86.6%, kappa = 0.73), respectively. RF IgM CIA and ELISA had a good qualitative agreement (86.5%, kappa = 0.73); RF IgA CIA and ELISA showed a moderate total agreement (78.5%, kappa = 0.53). When combinatory analyses were performed, the likelihood of RA increased with dual positivity and triple positivity and combining different markers resulted in higher odds ratio than the individual markers in all cases. ACPA and RF showed good clinical performance in this large Swiss cohort of RA patients and controls. Overall, the performance of CCP3 was superior to CCP2. The combination of these biomarkers in an interval model represents a potential tool for the diagnosis of RA patients.

Diagnostic utility of, and influence of tobacco usage and genetic predisposition on, immunoglobulin A, rheumatoid factor and anti-citrullinated peptide auto-antibodies in South African rheumatoid arthritis patients.

The immunoglobulin A isotypes of anti-cyclic citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF) are associated with disease severity and progression in Caucasian rheumatoid arthritis (RA) patients, as well as with genetic predisposition and tobacco use. To compare levels of ACPA-IgA and RF-IgA with those of ACPA-IgG and cRF in a cohort of black South African RA patients and healthy controls.To investigate the relationship between IGA autoantibodies and disease severity, genetic predisposition and tobacco use. RF-IgA and ACPA-IgA were determined in a cohort of predominantly black South African RA patients (n=75) in relation to serodiagnostic and prognostic potential, as well as tobacco use and genetic predisposition. Healthy control subjects were included to determine sensitivity, specificity and predictive values.ACPA-IgG/IgA and RF-IgA were determined by enzyme immunoassay and hs-CRP and cRF by nephelometry. Cotinine levels were determined by ELISA. The frequencies of ACPA-IgA and RF-IgA were 31% and 88% respectively compared to 88% for both types of traditional autoantibody procedures. ACPA-IgA was significantly higher (p=0.007) in patients with short disease duration, while linear regression analysis revealed a positive relationship with baseline disease activity scores. Levels of ACPA-IgG and ACPA-IgA were significantly higher in tobacco users who carried the HLA shared epitope. Although lacking in serodiagnostic superiority over cRF and ACPA-IgG, inclusion of RF-IgA and ACPA-IgA in autoantibody panels may provide insights into disease pathogenesis, interactions between tobacco usage and HLA genotype in the production of potentially disease-triggering ACPA-IgA antibodies.

PMS26 - Costs and Trends in the Usage of Biological Therapy for Rheumatoid Arthritis - A Retrospective Study

Rheumatoid arthritis (RA) autoimmune disorder is characterized by joint pain, stiffness, and impaired functionality. The disease is characterized for its variability in terms of the cost therapy, especially the biological one, compared to other treatment alternatives. We aimed to examine the costs in patients with RA receiving biological therapy and to describe global change in Disease Activity Score 28 (DAS28). Under a T2T model, we followed patients with RA receiving biological therapy during 12 months; each patient had a minimum of 6 follow-up visits. Clinical follow-up was defined according to DAS28 as follows: every 3-5 weeks (DAS28>5.1), every 7-9 weeks (DAS28≥3.1 and ≤5.1), and every 11-13 weeks (DAS28< 3.1). Tender joint count, swollen joint count and DAS28 were measured on each visit. We stratified patients in four groups: remission, low disease activity (LDA), moderate disease activity (MDA) and severe disease activity (SDA). Means and standard deviations were estimated for continuous variables and categorical variables were presented as percentages. We assessed the overall drug expenses; costs were presented in US dollars at the official rate of exchange for December 2017. 606 were included, 83% were female, mean age was 60 years ±11. We achieved remission in 29.63 % of patients, and 22.56% in LDA (at overall 52.2% of response rate). Regarding therapy, 27% received Certolizumab, followed by Etanercept 17%, Abatacept 13%, Rituximab 9% Tocilizumab 9%, Golimumab and Tofacitinib 7%, adalimumab 6% and infliximab 4%. The cost therapy for 12 months was 5.039.840 Million/Dollars for all patients. Our study showed an evident global improvement of DAS28 in a cohort of RA patients receiving biological therapy. Although the therapy is effective, ratios of cost-effectiveness should be considered by stakeholders; further research is needed using a greater sample to verify our results.

Factors affecting walking ability in female patients with rheumatoid arthritis.

ObjectiveTo determine the factors associated with gait parameters in female patients with rheumatoid arthritis (RA).MethodsThe gait analysis was performed in a large cohort of RA patients, and three basic gait parameters (step length, cadence and gait speed) were calculated. Clinical and laboratory data were also collected. Factors associated with gait parameters were analyzed using multivariable linear regression in the three models with forced entry. Then, we divided those patients with Health Assessment Questionnaire disability index (HAQ) scores ≤ 0.5 into two groups according to their gait speed that were compared to identify the characteristics of patients with a good HAQ score but poor walking ability.ResultsA total of 318 female patients were analyzed. Knee extension strength had the strongest positive association with all three gait parameters (P < 0.0001), while methotrexate use was also positively associated with all three gait parameters (step length: P < 0.05, cadence: P < 0.05 in model 1 and 2; P < 0.01 in model 3, gait speed: P < 0.01). The disease activity score was negatively associated with step length and gait speed (step length, gait speed: P < 0.01 in model 1 and 2; P < 0.05 in model 3). 26% of patients with good HAQ scores showed slow gait speed. Patients with good HAQ scores and slow gait speed had higher disease activity scores (P < 0.05) and lower knee extension strength (P < 0.0001) than those with good HAQ scores and normal gait speed.ConclusionsHigh knee extension strength, low disease activity and administration of methotrexate were strongly associated with good walking ability in female patients with RA. And, even if patients showed good HAQ scores, about quarter of those patients had poor walking ability, and they showed higher disease activity, lower knee extension strength, compared to the patients with normal gait speed.

Variables associated with subclinical atherosclerosis in a cohort of rheumatoid arthritis patients: Sex-specific associations and differential effects of disease activity and age.

ObjectiveTo advance the study of variables associated with subclinical atherosclerosis in rheumatoid arthritis (RA) with special consideration for the degree of disease activity, age and gender.MethodsThe carotid intima-media thickness (cIMT) and the presence of carotid atherosclerotic plaques along with clinical and biochemical characteristics were determined in 214 RA patients.ResultsAdjusted analysis reveals that men had a 0.059 mm significantly increased cIMT compared with women (p = 0.001; R2 = 3.8%) and that age was associated with cIMT (β = 0.0048 mm; p = 0.0001; R2 = 16%). Interestingly, we observed a significant interaction between gender and age. Thus, the effect of age on cIMT was significantly increased (12%) in men compared with women (p-value for interaction term = 0.041). Moreover, adjusted multivariable linear regression analysis revealed that disease activity score (DAS28) was significantly associated with cIMT in women (β = 0.021; p = 0.018: R2 = 0.03) but not men. In particular, women with high disease activity had a 0.079 mm increased cIMT compared with women in remission (p = 0.026). In addition, men in remission had a 0.134 mm increased cIMT compared with women in remission (p = 0.003; R2 = 8.7%). Active patients did not exhibit differences in cIMT values. Furthermore, 43% of patients presented carotid plaques. The variables independently associated with carotid plaques were age, smoking, health assessment questionnaire, erythrocyte sedimentation rate and rheumatoid factor (p<0.0001; R2 = 46%).ConclusionIn our cohort of patients with RA, DAS28 and age are differentially associated with cIMT in men and women. Our findings could explain the contradictory results that have previously been published in the literature.

Clinical Correlates, Outcomes, and Predictors of Inflammatory Ocular Disease Associated with Rheumatoid Arthritis in the Biologic Era.

Inflammatory ocular disease (IOD) is a rare but severe extraarticular manifestation of rheumatoid arthritis (ExRA) with high mortality. The aim of our study was to examine clinical characteristics of IOD in rheumatoid arthritis (RA) and their effect on disease severity and outcomes in recent years. A retrospective cohort of RA patients with IOD evaluated between 1996 and 2013 was assembled and compared to RA comparators without IOD and matched for age, sex, and disease duration. We identified 92 patients (69% female; mean age 62 yrs) with IOD: 33 scleritis, 23 episcleritis, 21 peripheral ulcerative keratitis (PUK), 14 uveitis, and 1 with orbital inflammation. The majority of patients with scleritis, episcleritis, and PUK was seropositive versus uveitis (> 80% vs 62%, p = 0.048). PUK and scleritis were more symptomatic compared to episcleritis and uveitis, and often required systemic therapy. Time to resolution was longer in scleritis than episcleritis (p = 0.01). PUK, scleritis, and uveitis had severe ocular sequelae. Prevalence of severe ExRA (18% vs 4%, p = 0.004) and dry eye syndrome (42% vs 26%, p = 0.024) was higher among patients with IOD than comparators. The incidence of new ExRA over 5-year followup was also higher among cases (29% vs 11%, p = 0.022). Ten-year survival was similar among RA patients with and without IOD (66% vs 64%, p = 0.56), with no differences noted among IOD subtypes. This large single-center study highlights the variable presentation and outcomes of IOD in RA. Although ocular complications are associated with significant morbidity, it is reassuring that survival among those with IOD is now similar to those without ocular disease.

Chronic disease list conditions in patients with rheumatoid arthritis in the private healthcare sector of South Africa.

Little is known about the burden of rheumatoid arthritis (RA) in South Africa. The aim of this study was to establish the prevalence of RA and coexisting chronic disease list (CDL) conditions in the private health sector of South Africa. A retrospective, cross-sectional analysis was performed on medicine claims data from 1 January 2014 to 31 December 2014 to establish the prevalence of RA. The cohort of RA patients was then divided into those with and those without CDL conditions, to determine the number and type of CDL conditions per patient, stratified by age group and gender. A total 4352 (0.5%) patients had RA, of whom 69.3% (3016) presented with CDL conditions. Patients had a median age of 61.31years (3.38; 98.51), and 74.8% were female. Patients with CDL conditions were older than those patients without (p < 0.001; Cohen's d = 0.674). Gender had no influence on the presence of CDL conditions (p = 0.456). Men had relatively higher odds for hyperlipidemia (OR 1.83; CI 1.33-2.51; p < 0.001) and lower odds for asthma (OR 0.83; CI 0.48-1.42; p = 0.490) than women. In combination with hyperlipidemia, the odds for asthma were reversed and strongly increased (OR 6.74; CI 2.07-21.93; p = 0.002). The odds for men having concomitant hyperlipidemia, hypertension, type 2 diabetes mellitus and hypothyroidism were insignificant and low (OR 0.40; CI 0.16-1.02; p = 0.055); however, in the absence of hypothyroidism, the odds increased to 3.26 (CI 2.25-4.71; p < 0.001). Hypothyroidism was an important discriminating factor for comorbidity in men with RA. This study may contribute to the body of evidence about the burden of RA and coexisting chronic conditions in South Africa.

Validation and reliability of the Timed Up and Go test for measuring objective functional impairment in patients with long-standing rheumatoid arthritis: a cross-sectional study.

This study aimed to validate the Timed Up and Go test (TUG) for measuring objective functional impairment in patients with established rheumatoid arthritis (RA) based on a prospective observational cohort of RA patients undergoing joint surgery. We collected data on demographics, Health Assessment Questionnaire Disability Index (HAQ-DI), and associations between TUG and HAQ-DI and other patient-reported outcomes, including European Quality of life scale (EQ-5D) were determined. Cut-off values of TUG for HAQ remission (HAQ-DI ≤0.5), normal HAQ (HAQ-DI ≤0.25), and the absence of disability in each HAQ-DI category were also determined by age. A total of 435 patients were enrolled and analyzed. Mean age was 64.2 years, mean disease duration was 17.1 years, mean HAQ-DI was 1.14, and mean TUG was 11.1 sec. TUG was significantly correlated with aging, EQ-5D, and HAQ-DI categories related to lower limb function (arising, walking, reach and activity). After adjusting for age and sex, mean TUG values were 9.0 sec (95% CI, 7.7-10.3) in patients with HAQ remission and 8.7 sec (7.4-10.4) in those with normal HAQ. By age, mean TUG values for HAQ remission were 7.2 sec (5.9-8.5) in young patients (≤61 years), 9.1 sec (7.6-10.5) in middle-aged patients (62-70 years) and 10.0 sec (5.7-14.2) in old patients (≥71 years). TUG was significantly associated with functional impairment and aging in patients with long-standing RA. Thus, TUG could be useful in setting treatment goals for joint surgery and rehabilitation in established RA patients.

The risk of malignancy and its incidence in early rheumatoid arthritis patients treated with biologic DMARDs

BackgroundTreatment with disease-modifying anti-rheumatic drugs (DMARDs) has raised concerns about the risk of malignancies in rheumatoid arthritis (RA) patients. However, the association between biologic DMARDs (bDMARDs) and malignancy in previous reports remains controversial. Therefore we aimed to estimate the incidence of malignancy in early RA patients and to evaluate the relative risk of malignancy with use of bDMARDs.MethodsA retrospective cohort of incident RA patients was established using the Korean National Claims Database. Among a total of 14,081 RA patients identified, 1684 patients with a history of malignancy were excluded. We calculated the incidence rate of overall and individual malignancies. The standardized incidence ratio (SIR) of malignancies in bDMARD users was compared to that in nonusers. Multivariable logistic regression analysis was used to evaluate the impact of bDMARDs on the development of malignancies in early RA patients.ResultsA total of 12,397 early RA patients without a history of malignancy were enrolled. During 41,599 person-years (PY) of follow-up, 725 malignancies developed in 561 patients (174.3/10,000 PY) and 21 hematologic malignancies developed (5.0/10,000 PY). Patients treated with bDMARDs had a significantly lower incidence of overall malignancy compared to those not treated with bDMARDs (SIR 0.45 (95% CI 0.28–0.70)). However, this relationship was not significant with regard to hematologic malignancies (SIR 2.65 (95% CI 0.55–7.76)). On multivariable analysis, bDMARD use was a protective factor against the development of overall malignancy (odds ratio 0.42 (95% CI 0.25–0.73)). However, bDMARD use had no significant protective effect against the development of hematologic malignancies (odds ratio 1.69 (95% CI 0.38–7.59)).ConclusionsIn early RA patients, bDMARD use decreases the overall risk of developing malignancies; however, it does not affect the risk of developing hematologic malignancies.

Disease activity trajectories in early rheumatoid arthritis following intensive DMARD therapy over 3 years: association with persistence to therapy.

To identify the disease activity trajectories during intensive triple disease modifying anti-rheumatic drug (DMARD) therapy over 3 years in rheumatoid arthritis (RA) patients and to evaluate the association with treatment persistence. Disease Activity Score in 28 joints, baseline risk factors and medication usage were obtained from a longitudinal observational cohort of early RA patients, most of whom were treated with combination DMARD therapy consisting of methotrexate, sulfasalazine and hydroxychloroquine. Persistence of each DMARD was defined as the duration of time from initiation to cessation. A group-based trajectory modelling technique was used to identify disease activity trajectories. Three disease activity trajectories (good [43.8%], moderate [39.7%] and poor [16.5%]) were identified in a cohort of 297 patients. Most baseline risk factors, medication usage, the rate of treatment persistence and the effect of persistence on disease activity differed among patients in each of the three trajectories. Although the rate of persistence was higher in the trajectory with a good outcome, the association with persistence was more pronounced among patients who were in the poor outcome trajectory. Persistence with at least two or all three baseline DMARDs was associated with a decrease in disease activity to a broadly similar degree in all trajectories. After correction for other baseline prognostic factors, persistence with initial DMARDs contributes to heterogeneity in disease activity trajectory and there was an association between persistence with initial DMARD therapy and lower long-term disease activity.

Patient\u2019s perspective of sustained remission in rheumatoid arthritis

BackgroundDuring the course of rheumatoid arthritis (RA), patients have profound negative effects on their patient-reported-outcomes (PRO); in addition, the impact of sustained remission (SR) on PROs may differ for each particular outcome. The objectives of this study were to identify SR from an inception cohort of RA patients and to examine the impact of SR in an ample spectrum of PROs.MethodsThe study was developed in a well characterized and ongoing cohort of RA patients with recent onset disease recruited from 2004 onwards. In November 2016, the cohort included 187 patients, of whom 145 had at least 30 months of follow-up, with complete rheumatic assessments at regular intervals in addition to a pain visual analogue scale (PVAS), overall disease-VAS (OVAS), health assessment questionnaire (HAQ), Short-Form 36v2 Survey (SF-36) and fatigue assessment. First SR was defined according to the DAS28 cut-offs (DAS28-SR) and ACR/EULAR 2011 Boolean definition (B-SR), if maintained for at least 12 consecutive months. The dependent t test and Mc Nemar’s tests were used for comparisons between related groups. Local IRB approval was obtained.ResultsMore patients achieved DAS28-SR than B-SR: 78 vs. 63, respectively. Fifty patients met both SR definitions. Follow-up to DAS28-SR was shorter than to B-SR and the duration of DAS28-SR was longer, p ≤ 0.023 for all comparisons.At SR, patients had PRO proxy to normal values; the percentage of patients with normal PRO varied from 97% (95% CI: 91–99) for HAQ to 50% (95% CI: 39–61) for absence of fatigue.In DAS28-SR patients, acute reactant phases within the normal range were detected very early (after 1.5–2.9 months). HAQ, PVAS, OVAS and SF-36 were scored within the normal range after 6–7 months. The absence of fatigue was detected at 8.7 months of follow-up, which was similar to DAS28-SR. In the 63 patients with B-SR, a similar pattern was observed. The follow-up to outcomes of the 50 patients who met both SR definitions was similar, but the absence of fatigue and physical component SF-36 normalization were achieved earlier in B-SR patients (p ≤ 0.02).ConclusionsThe impact of SR on PRO differs accordingly to each particular outcome.