Levels of anti-citrullinated protein antibodies and IgM rheumatoid factor are not associated with outcome in early arthritis patients: a cohort study

Introduction  

To investigate whether baseline levels of anti-citrullinated protein antibody (ACPA) or IgM rheumatoid factor (IgM-RF) and changes in the year thereafter are associated with disease activity, functional and radiographic outcome in early arthritis patients, and provide additional information over baseline autoantibody status.     

Protein,iron, and meat consumption and risk for rheumatoid arthritis: a prospective cohort study

A recent prospective study showed that higher consumption of red meat and total protein was associated with increased risk for inflammatory polyarthritis. We therefore prospectively examined the relationship between diet (in particular, protein, iron, and corresponding food sources) and incident rheumatoid arthritis (RA) among 82,063 women in the Nurses' Health Study. From 1980 to 2002, 546 incident cases of RA were confirmed by a connective tissue disease screening questionnaire and medical record review for American College of Rheumatology criteria for RA. Diet was assessed at baseline in 1980 and five additional times during follow up. We conducted Cox proportional hazards analyses to calculate the rate ratio of RA associated with intakes of protein (total, animal, and vegetable) and iron (total, dietary, from supplements, and heme iron) and their primary food sources, adjusting for age, smoking, body mass index, and reproductive factors. The multivariate models revealed no association between RA and any measure of protein or iron intake. In comparisons of highest with lowest quintiles of intake, the rate ratio for total protein was 1.17 (95% confidence interval 0.89–1.54; P for trend = 0.11) and for total iron it was 1.04 (95% confidence interval 0.77–1.41; P for trend = 0.82). Red meat, poultry, and fish were also not associated with RA risk. We were unable to confirm that there is an association between protein or meat and risk for RA in this large female cohort. Iron was also not associated with RA in this cohort.     

Mannose-binding lectin deficiency is associated with early onset of polyarticular juvenile rheumatoid arthritis: a cohort study

Background  

Mannose-binding lectin (MBL) is an innate immune protein. The aim of our study was to determine whether genetically determined MBL deficiency is associated with susceptibility to juvenile rheumatoid arthritis (JRA) and whether MBL2 genotypes are associated with JRA severity.     

Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study

Introduction

We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care.

Methods

The study involved a clinical assessment by a rheumatologist and a self-report questionnaire by patients. The clinical assessment included a review of clinical features of RA and exposure to DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included myocardial infarction, angina, coronary disease, coronary bypass surgery, and stroke. Traditional risk factors recorded were hypertension, hyperlipidemia, diabetes mellitus, smoking, physical inactivity, and body mass index. Unadjusted and adjusted hazard ratios (HRs) (95% confidence interval [CI]) for CV morbidity were calculated using Cox proportional hazard regression models.

Results

Between January 2005 and October 2006, the QUEST-RA project included 4,363 patients from 48 sites in 15 countries; 78% were female, more than 90% were Caucasian, and the mean age was 57 years. The prevalence for lifetime CV events in the entire sample was 3.2% for myocardial infarction, 1.9% for stroke, and 9.3% for any CV event. The prevalence for CV risk factors was 32% for hypertension, 14% for hyperlipidemia, 8% for diabetes, 43% for ever-smoking, 73% for physical inactivity, and 18% for obesity. Traditional risk factors except obesity and physical inactivity were significantly associated with CV morbidity. There was an association between any CV event and age and male gender and between extra-articular disease and myocardial infarction. Prolonged exposure to methotrexate (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0.59; 95% CI 0.43 to 0.79), sulfasalazine (HR 0.92; 95% CI 0.87 to 0.98), glucocorticoids (HR 0.95; 95% CI 0.92 to 0.98), and biologic agents (HR 0.42; 95% CI 0.21 to 0.81; P < 0.05) was associated with a reduction of the risk of CV morbidity; analyses were adjusted for traditional risk factors and countries.

Conclusion

In conclusion, prolonged use of treatments such as methotrexate, sulfasalazine, leflunomide, glucocorticoids, and tumor necrosis factor-alpha blockers appears to be associated with a reduced risk of CV disease. In addition to traditional risk factors, extra-articular disease was associated with the occurrence of myocardial infarction in patients with RA.     

Anti-cyclic citrullinated peptide antibody titer predicts time to rheumatoid arthritis onset in patients with undifferentiated arthritis: results from a 2-year prospective study

Introduction

The diagnostic, predictive and prognostic role of anti-cyclic citrullinated peptide (CCP) antibodies in rheumatoid arthritis (RA) patients is widely accepted. Moreover, detection of these antibodies in subjects presenting with undifferentiated arthritis (UA) is associated with a significant risk to develop the disease. On the other hand, clinical and prognostic significance of evaluating anti-CCP levels in subjects with inflammatory arthritis at disease onset has not been fully clarified. The goal of this prospective study is to analyze the value and prognostic significance of anti-CCP titer quantification in UA subjects.

Methods

Serial anti-CCP assays were measured in 192 consecutive patients presenting with UA lasting less than 12 weeks. Clinical and serological data and arthritis outcome were evaluated every 6 months until two years of follow-up.

Results

Anti-CCP positivity, at both low and high titer, and arthritis of hand joints significantly predicted RA at two years, risk increasing in subjects with high anti-CCP titers at baseline. Moreover, time to RA diagnosis was shorter in patients with high anti-CCP2 titers at enrollment with respect to those with low antibody concentration.

Conclusions

Presence of anti-CCP antibodies, at both low and high concentration, is significantly associated with RA development in subjects with recent onset UA. However, time interval from the onset of the first symptoms to the fulfilment of the classification criteria appears to be directly related to the initial anti-CCP level.     

Plasmodium vivax and mixed infections are associated with severe malaria in children: a prospective cohort study from Papua New Guinea

Background

Severe malaria (SM) is classically associated with Plasmodium falciparum infection. Little information is available on the contribution of P. vivax to severe disease. There are some epidemiological indications that P. vivax or mixed infections protect against complications and deaths. A large morbidity surveillance conducted in an area where the four species coexist allowed us to estimate rates of SM among patients infected with one or several species.

Methods and Findings

This was a prospective cohort study conducted within the framework of the Malaria Vaccine Epidemiology and Evaluation Project. All presumptive malaria cases presenting at two rural health facilities over an 8-y period were investigated with history taking, clinical examination, and laboratory assessment. Case definition of SM was based on the World Health Organization (WHO) criteria adapted for the setting (i.e., clinical diagnosis of malaria associated with asexual blood stage parasitaemia and recent history of fits, or coma, or respiratory distress, or anaemia [haemoglobin < 5 g/dl]). Out of 17,201 presumptive malaria cases, 9,537 (55%) had a confirmed Plasmodium parasitaemia. Among those, 6.2% (95% confidence interval [CI] 5.7%–6.8%) fulfilled the case definition of SM, most of them in children <5 y. In this age group, the proportion of SM was 11.7% (10.4%–13.2%) for P. falciparum, 8.8% (7.1%–10.7%) for P. vivax, and 17.3% (11.7%–24.2%) for mixed P. falciparum and P. vivax infections. P. vivax SM presented more often with respiratory distress than did P. falciparum (60% versus 41%, p = 0.002), but less often with anaemia (19% versus 41%, p = 0.0001).

Conclusion

P. vivax monoinfections as well as mixed Plasmodium infections are associated with SM. There is no indication that mixed infections protected against SM. Interventions targeted toward P. falciparum only might be insufficient to eliminate the overall malaria burden, and especially severe disease, in areas where P. falciparum and P. vivax coexist.     

Risk of osteoporotic fracture in a large population-based cohort of patients with rheumatoid arthritis

Introduction  

Although osteoporosis has been reported to be more common in patients with rheumatoid arthritis (RA), little is known whether the risk of osteoporotic fractures in these patients differs by age, sex, and anatomic site.     

A simple algorithm to predict the development of radiological erosions in patients with early rheumatoid arthritis: prospective cohort study.

OBJECTIVE: To produce a practical algorithm to predict which patients with early rheumatoid arthritis will develop radiological erosions. DESIGN: Primary care based prospective cohort study. SETTING: All general practices in the Norwich Health Authority, Norfolk. SUBJECTS: 175 patients notified to the Norfolk Arthritis Register were visited by a metrologist soon after they had presented to their general practitioners with inflammatory polyarthritis, and again after a further 12 months. All the patients satisfied the American Rheumatism Association''s 1987 criteria for rheumatoid arthritis and were seen by a metrologist within six months of the onset of symptoms. The study population was randomly split into a prediction sample (n = 105) for generating the algorithm and a validation sample (n = 70) for testing it. MAIN OUTCOME MEASURES: Predictor variables measured at baseline included rheumatoid factor status, swelling of specific joint areas, duration of morning stiffness, nodules, disability score, age, sex, and disease duration when the patient first presented. The outcome variable was the presence of radiological erosions in the hands or feet, or both, after 12 months. RESULTS: A simple algorithm based on a combination of three variables--a positive rheumatoid factor test, swelling of at least two large joints, and a disease duration of more than three months--was best able to predict erosions. When the accuracy of this algorithm was tested with the validation sample, the erosion status of 79% of patients was predicted correctly. CONCLUSIONS: A simple algorithm based on three easily measured items of information can predict which patients are at high risk and which are at low risk of developing radiological erosions.     

Calprotectin strongly and independently predicts relapse in rheumatoid arthritis and polyarticular psoriatic arthritis patients treated with tumor necrosis factor inhibitors: a 1-year prospective cohort study

Background

Calprotectin is a biomarker of disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) and predicts relapse in juvenile idiopathic arthritis. Higher drug trough serum levels are associated with a good response in patients treated with tumor necrosis factor inhibitors (TNFi). Power Doppler ultrasound synovitis is predictive of relapse and structural damage progression in patients in clinical remission. The purpose of this study was to analyze the accuracy of serum calprotectin levels, drug trough serum levels (TSL), and power Doppler (PD) activity as predictors of relapse in RA and PsA patients in remission or with low disease activity receiving TNFi.

Methods

This was a longitudinal, prospective, 1-year single-center study of 103 patients (47 RA, 56 PsA) receiving TNFi in remission or with low disease activity (28-joint Disease Activity Score (DAS28)?≤?3.2). The predictive value of serum calprotectin, TNFi TSL, and PD were assessed using receiver operating characteristic (ROC) analyses. To illustrate the predictive performance of calprotectin, TNFi TSL, and PD score, Kaplan-Meier curves were constructed from baseline to relapse. Associations between baseline factors and relapse were determined using Cox regression models. Multivariate models were constructed to analyze the effect of covariates and to fully adjust the association between calprotectin, TNFi TSL, and PD score with relapse. A generalized estimating equation model with an identity link for longitudinal continuous outcomes was used to assess the effect of covariates on TNFi TSL.

Results

Ninety-five patients completed 1 year of follow-up, of whom 12 experienced a relapse. At baseline, relapsers had higher calprotectin levels, lower TNFi TSL, and higher PD activity than nonrelapsers. ROC analysis showed calprotectin fully predicted relapse (area under the curve (AUC)?=?1.00). TNFi TSL and PD had an AUC of 0.790 (95% confidence interval (CI) 0.691–0.889) and 0.877 (95% CI 0.772–0.981), respectively. Survival analyses and log rank tests showed significant differences between groups according to calprotectin serum levels (p?<?0.001), TNFi TSL (p?=?0.004), and PD score (p?<?0.001). Univariate Cox regression models showed that time-to-remission/low disease activity (hazard ratio (HR)?=?1.17, p?<?0.001), calprotectin levels (HR?=?2.38, p?<?0.001), TNFi TSL (HR?=?0.47, p?=?0.018), and PD score (HR?=?1.31, p?<?0.001) were significantly associated with disease relapse. In the multivariate analysis, only baseline calprotectin levels independently predicted disease relapse (HR?=?2.41, p?=?0.002). The generalized estimating equation analysis showed that only disease activity by DAS28-erythrocyte sedimentation rate (ESR) was significantly associated with longitudinal changes in TNFi TSL (regression coefficient 0.26 (0.0676 to 0.0036), p?=?0.001).

Conclusion

Time-to-remission/low disease activity, calprotectin serum levels, TNFi TSL, and PD score were significantly associated with disease relapse. However, only baseline calprotectin serum levels independently predicted disease relapse in RA and PsA patients under TNFi therapy.

     

Early medication use in new-onset rheumatoid arthritis may delay joint replacement: results of a large population-based study

IntroductionUse of disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) may prevent joint damage and potentially reduce joint replacement surgeries. We assessed the association between RA drug use and joint replacement in Quebec, Canada.MethodsA cohort of new-onset RA patients was identified from Quebec’s physician billing and hospitalization databases from 2002–2011. The outcome was defined using procedure codes submitted by orthopedic surgeons. Medication use was obtained from pharmacy databases. We used alternative Cox regression models with time-dependent variables measuring the cumulative effects of past use during different time windows (one model focussing on the first year after cohort entry) for methotrexate (MTX), and other DMARDs. Models were adjusted for baseline sociodemographics, co-morbidity and prior health service use, time-dependent cumulative use of other drugs (anti-tumor necrosis factor [anti-TNF] agents, other biologics, cyclooxygenase-2 inhibitors [COXIBs], nonselective nonsteroidal antiinflammatory drugs [NSAIDs], and systemic steroids), and markers of disease severity.ResultsDuring follow-up, 608 joint replacements occurred among 11,333 patients (median follow-up: 4.6 years). The best-fitting model relied on the cumulative early use (within the first year after cohort entry) of MTX and of other DMARDs, with an interaction between MTX and other DMARDs. In this model, greater exposure within the first year, to either MTX (adjusted hazard ratio, HR = 0.95 per 1 month, 95 % confidence interval, 95 % CI 0.93-0.97) or other DMARDs (HR = 0.97, 95 % CI 0.95-0.99) was associated with longer time to joint replacement.ConclusionsOur results suggest that longer exposure to either methotrexate (MTX) or other DMARDs within the first year after RA diagnosis is associated with longer time to joint replacement surgery.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0713-3) contains supplementary material, which is available to authorized users.     

Physical activity and risk of rheumatoid arthritis in women: a population-based prospective study

IntroductionOnly one study has analysed the association between exercise and development of rheumatoid arthritis (RA), showing no association. Aim of this paper was to evaluate the association of physical activity in all its aspect with RA.MethodsTo examine this association, middle age and elderly women from the Swedish Mammography Cohort, a population-based prospective study, were analysed. Data on physical activity were collected in 1997 by self-administrated food-frequency questionnaire. Risk of RA associated with physical activity was estimated using Cox proportional hazard regression models.ResultsAmong 30,112 women born between 1914 and 1948 followed-up from January 1, 2003 to December 31, 2010, 201 RA cases were identified (226,477 person-years). There was a statistically significant 35% lower risk of RA (relative risk (RR), 0.65; 95% confidence interval (CI), 0.43-0.96) among women in the highest category of leisure-time activity (combining more than 20 minute per day of walking/bicycling (median 40–60 minute per day) and more than 1 hour per week of exercise (median 2–3 hours per week)) as compared to women in the lowest category (less than 20 minute per day of walking/bicycling and less than 1 hour per week of exercise). A non-statistically significant decreased risk was observed for household work (−32%) and work/occupation (−15%), while an increased risk was observed for leisure-time physical inactivity (+27%). Daily energy expenditure was not associated with risk of RA.ConclusionsThis prospective population-based cohort study of women supports the hypothesis that physical activity can be a protective factor in the etiology of rheumatoid arthritis. Our results add to accumulated evidence on benefits of modifiable leisure-time physical activity for prevention of many other chronic diseases.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0560-2) contains supplementary material, which is available to authorized users.     

Adherence to a treat-to-target strategy in early rheumatoid arthritis: results of the DREAM remission induction cohort

Introduction

Clinical trials have demonstrated that treatment-to-target (T2T) is effective in achieving remission in early rheumatoid arthritis (RA). However, the concept of T2T has not been fully implemented yet and the question is whether a T2T strategy is feasible in daily clinical practice. The objective of the study was to evaluate the adherence to a T2T strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) < 2.6) in early RA in daily practice. The recommendations regarding T2T included regular assessment of the DAS28 and advice regarding DAS28-driven treatment adjustments.

Methods

A medical chart review was performed among a random sample of 100 RA patients of the DREAM remission induction cohort. At all scheduled visits, it was determined whether the clinical decisions were compliant to the T2T recommendations.

Results

The 100 patients contributed to a total of 1,115 visits. The DAS28 was available in 97.9% (1,092/1,115) of the visits, of which the DAS28 was assessed at a frequency of at least every three months in 88.3% (964/1,092). Adherence to the treatment advice was observed in 69.3% (757/1,092) of the visits. In case of non-adherence when remission was present (19.5%, 108/553), most frequently medication was tapered off or discontinued when it should have been continued (7.2%, 40/553) or treatment was continued when it should have been tapered off or discontinued (6.2%, 34/553). In case of non-adherence when remission was absent (42.1%, 227/539), most frequently medication was not intensified when an intensification step should have been taken (34.9%, 188/539). The main reason for non-adherence was discordance between disease activity status according to the rheumatologist and DAS28.

Conclusions

The recommendations regarding T2T were successfully implemented and high adherence was observed. This demonstrates that a T2T strategy is feasible in RA in daily clinical practice.     

Increased mortality associated with HTLV-II infection in blood donors: a prospective cohort study

Background

The Sykes' monkey and related forms (Cercopithecus mitis) make up an abundant, widespread and morphologically diverse species complex in eastern Africa that naturally harbors a distinct simian immunodeficiency virus (SIVsyk). We carried out a retrospective serological survey of SIV infection from both wild and captive Sykes' monkeys from Kenya. We compared two commercially available, cross-reactive ELISA tests using HIV antigens with a novel SIVsyk antigen-specific Western blot assay and analyzed the data by origin, subspecies, age and sex.

Results

The SIVsyk antigen-specific Western blot assay detected more serum samples as positive than either of the cross-reactive ELISA assays. Using this assay, we found that seroprevalence is higher than previously reported, but extremely variable in wild populations (from 0.0 to 90.9%). Females were infected more often than males in both wild and captive populations. Seropositive infants were common. However, no seropositive juveniles were identified.

Conclusion

We have developed a specific and sensitive Western blot assay for anti-SIVsyk antibody detection. Sykes' monkeys are commonly infected with SIVsyk, but with extremely variable prevalence in the wild. Higher infection prevalence in females suggests predominantly sexual transmission. High infection prevalence in infants, but none in juveniles, suggests maternal antibodies, but little or no vertical transmission.     

Disease-modifying antirheumatic drugs are associated with a reduced risk for cardiovascular disease in patients with rheumatoid arthritis: a case control study

Rheumatoid arthritis (RA) is characterized by inflammation and an increased risk for cardiovascular disease (CVD). This study investigates possible associations between CVD and the use of conventional disease-modifying antirheumatic drugs (DMARDs) in RA. Using a case control design, 613 RA patients (5,649 patient-years) were studied, 72 with CVD and 541 without CVD. Data on RA, CVD and drug treatment were evaluated from time of RA diagnosis up to the first cardiovascular event or the end of the follow-up period. The dataset was categorized according to DMARD use: sulfasalazine (SSZ), hydroxychloroquine (HCQ) or methotrexate (MTX). Odds ratios (ORs) for CVD, corrected for age, gender, smoking and RA duration, were calculated per DMARD group. Patients who never used SSZ, HCQ or MTX were used as a reference group. MTX treatment was associated with a significant CVD risk reduction, with ORs (95% CI): 'MTX only', 0.16 (0.04 to 0.66); 'MTX and SSZ ever', 0.20 (0.08 to 0.51); and 'MTX, SSZ and HCQ ever', 0.20 (0.08 to 0.54). The risk reductions remained significant after additional correction for the presence of rheumatoid factor and erosions. After correction for hypertension, diabetes and hypercholesterolemia, 'MTX or SSZ ever' and 'MTX, SSZ and HCQ ever' showed significant CVD risk reduction. Rheumatoid factor positivity and erosions both increased CVD risk, with ORs of 2.04 (1.02 to 4.07) and 2.36 (0.92 to 6.08), respectively. MTX and, to a lesser extent, SSZ were associated with significantly lower CVD risk compared to RA patients who never used SSZ, HCQ or MTX. We hypothesize that DMARD use, in particular MTX use, results in powerful suppression of inflammation, thereby reducing the development of atherosclerosis and subsequently clinically overt CVD.     

Association of a quality improvement program with neonatal outcomes in extremely preterm infants: a prospective cohort study

Background:

We previously demonstrated improvement in bronchopulmonary dysplasia and nosocomial infection among preterm infants at 12 neonatal units using the Evidence-based Practice for Improving Quality (EPIQ). In the current study, we assessed the association of Canada-wide implementation of EPIQ with mortality and morbidity among preterm infants less than 29 weeks gestational age.

Methods:

This prospective cohort study included 6026 infants admitted to 25 Canadian units between 2008 and 2012 (baseline year, n = 1422; year 1, n = 1611; year 2, n = 1508; year 3, n = 1485). Following a 1-year baseline period and 6 months of training and planning, EPIQ was implemented over 3 years. Our primary outcome was a composite of neonatal mortality and any of bronchopulmonary dysplasia, severe neurologic injury, severe retinopathy of prematurity, necrotizing enterocolitis and nosocomial infection. We compared outcomes for baseline and year 3 using multivariable analyses.

Results:

In adjusted analyses comparing baseline with year 3, the composite outcome (70% v. 65%; adjusted odds ratio [OR] 0.63, 95% confidence interval [CI] 0.51 to 0.79), severe retinopathy (17% v. 13%; OR 0.60, 95% CI 0.45 to 0.79), necrotizing enterocolitis (10% v. 8%; OR 0.73, 95% CI 0.52 to 0.98) and nosocomial infections (32% v. 24%; OR 0.63, 95% CI 0.48 to 0.82) were significantly reduced. The composite outcome was lower among infants born at 26 to 28 weeks gestation (62% v. 52%; OR 0.62, 95% CI 0.49 to 0.78) but not among infants born at less than 26 weeks gestational age (90% v. 88%; OR 0.73, 95% CI 0.44 to 1.20).

Interpretation:

EPIQ methodology was generalizable within Canada and was associated with significantly lower likelihood of the composite outcome, severe retinopathy, necrotizing enterocolitis and nosocomial infections. Infants born at 26 to 28 weeks gestational age benefited the most.Rates of neonatal mortality and morbidity have not improved substantially over the past decade, despite advances in neonatal and perinatal care.^1–3 To improve infant outcomes, quality improvement initiatives have been implemented in neonatal units, but their success has varied.^4–6 A common approach is to form collaborative neonatal networks and to use quality improvement methods to address variations in practice and outcomes.^7–9 Commonly used quality improvement methods include identifying the best available evidence, adapting practice change to the organization, collaborative learning, and audit and feedback of information implemented in iterative “plan, do, study, act” cycles.¹⁰We previously developed and tested the Evidence-based Practice for Improving Quality (EPIQ) in 12 neonatal units in a cluster randomized trial.¹¹ EPIQ is a multifaceted quality improvement approach that combines the best available evidence with institution-specific data to identify institution-specific needs. Sites targeting nosocomial infection achieved a 32% reduction in infections, and sites targeting bronchopulmonary dysplasia achieved a 15% reduction in that condition. Five units that did not participate formed a comparison group and showed no improvement for either outcome.¹¹In the current study, our objective was to assess the generalizability of EPIQ to other neonatal units in Canada and to determine any association with improvements in mortality and morbidity among preterm neonates born at less than 29 weeks gestational age.     

Disease evolution in mixed connective tissue disease: results from a long-term nationwide prospective cohort study

Background

The phenotypic stability of mixed connective tissue disease (MCTD) is not clear, and knowledge about disease activity and remission is scarce. We aimed to establish the occurrence of evolution from MCTD to another defined rheumatic condition, and the prevalence and durability of remission after long-term observation.

Methods

In this large population-based prospective observational MCTD cohort study (N?=?118), disease conversion was defined by the development of new auto-antibodies and clinical features compliant with another well-defined rheumatic condition. Remission was defined by a combination of systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K) of 0 and European League Against Rheumatism scleroderma trials and research (EUSTAR) activity index <2.5. Predictors of phenotypic stability and disease remission were assessed by logistic regression.

Results

Among 118 patients, 14 (12%) developed another well-defined rheumatic condition other than MCTD after mean disease duration of 17 (SD 9) years. Puffy hands predicted a stable MCTD phenotype in univariable regression analysis (OR 7, CI 2–27, P?=?.010). Disease activity defined by SLEDAI-2 K, decreased gradually across the observation period and?>?90% of patients had EUSTAR activity index <2.5. There were 13% patients in remission throughout the whole mean observation period of 7 (SD 2) years. The strongest predictor of remission was percentage of predicted higher forced vital capacity.

Conclusions

Our results strengthen the view of MCTD as a relatively stable disease entity. Long-term remission in MCTD is not frequent; however, the low SLEDAI-2 K and EUSTAR scores during the observation period suggests that the disease runs a milder course than systemic lupus erythematosus and systemic sclerosis.

     

Rituximab in patients with rheumatoid arthritis in routine practice (GERINIS): six-year results from a prospective,multicentre, non-interventional study in 2,484 patients

Introduction

The aim of this study was to evaluate the safety and efficacy of rituximab (RTX) in a large cohort of patients with rheumatoid arthritis in routine care, and to monitor changes in daily practice since the introduction of RTX therapy.

Methods

This was a multicentre, prospective, non-interventional study conducted under routine practice conditions in Germany. Efficacy was evaluated using Disease Activity Score in 28 joints (DAS28) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Safety was assessed by recording adverse drug reactions (ADRs). Physician and patient global efficacy and tolerability assessments were also evaluated.

Results

Overall, 2,484 patients (76.7% female, mean age 56.4 years, mean disease duration 11.7 years) received RTX treatment (22.7% monotherapy). The total observation period was approximately six-years (median follow-up 14.7 months). RTX treatment led to improvements in DAS28 and HAQ-DI that were sustained over multiple courses. DAS28 improvements positively correlated with higher rheumatoid factor levels up to 50 IU/ml. Response and tolerability were rated good/very good by the majority of physicians and patients. Mean treatment intervals were 10.5 and 6.8 months for the first and last 400 enrolled patients, respectively. Infections were the most frequently reported ADRs (9.1%; 11.39/100 patient-years); approximately 1% of patients per course discontinued therapy due to ADRs.

Conclusions

Prolonged RTX treatment in routine care is associated with good efficacy and tolerability, as measured by conventional parameters and by physicians’ and patients’ global assessments. Rheumatoid factor status served as a distinct and quantitative biomarker of RTX responsiveness. With growing experience, physicians repeated treatments earlier in patients with less severe disease activity.     

Poor knowledge of methotrexate associated with older age and limited English-language proficiency in a diverse rheumatoid arthritis cohort

Introduction

Our objective was to determine rheumatoid arthritis (RA) patients’ understanding of methotrexate and assess whether knowledge varies by age, education, English language proficiency, or other disease-related factors.

Methods

Adults with RA (n = 135) who were enrollees of an observational cohort completed a structured telephone interview in their preferred language between August 2007 and July 2009. All subjects who reported taking methotrexate were asked 11 questions about the medication in addition to demographics, education level, and language proficiency. Primary outcome was a total score below the 50^th percentile (considered inadequate methotrexate knowledge). Bivariable and multivariable logistic regressions were performed. Covariates included demographics, language proficiency, education, and disease characteristics.

Results

Of 135 subjects, 83% were female, with a mean age of 55 ± 14 years. The majority spoke English (64%), followed by 22% Spanish and 14% Cantonese or Mandarin. Limited English language proficiency (LEP) was reported in 42%. Mean methotrexate knowledge score was 5.4 ± 2.6 (range, 0 to 10); 73 (54%) had a score lower than 5 (of 10). Age older than 55, less than high school education, LEP, better function, and biologic use were independently associated with poor knowledge.

Conclusions

In a diverse RA cohort, overall methotrexate knowledge was poor. Older age and limited proficiency in English were significant correlates of poor knowledge. Identification of language barriers and improved clinician-patient communication around methotrexate dosing and side effects may lead to improved safety and enhanced benefits of this commonly used RA medication.     

Usage of skin care products and risk of rheumatoid arthritis: results from the Swedish EIRA study

Introduction

The aim of this study was to investigate the association between exposure to cosmetics, often containing mineral oil, and the risk of developing rheumatoid arthritis (RA). The study was performed against the background that occupational exposure to mineral oil has recently been shown to be associated with an increased risk for RA in man, and that injection of or percutaneous exposure to mineral-oil-containing cosmetics can induce arthritis in certain rat strains.

Methods

A population-based case-control study of incident cases of RA was performed among the population aged 18 to 70 years in a defined area of Sweden during May 1996 to December 2003. A case was defined as an individual from the study base, who received for the first time a diagnosis of RA according to the 1987 American College of Rheumatology criteria. Controls were randomly selected from the study base with consideration taken for age, gender and residential area. Cases (n = 1,419) and controls (n = 1,674) answered an extensive questionnaire regarding environmental and lifestyle factors including habits of cosmetic usage. The relative risk of developing RA was calculated for subjects with different cosmetic usage compared with subjects with low or no usage. Analysis was also performed stratifying the cases for presence/absence of rheumatoid factor and antibodies to citrulline-containing peptides.

Results

The relative risks of developing RA associated with use of cosmetics were all close to one, both for women and men, for different exposure categories, and in relation to different subgroups of RA.

Conclusion

This study does not support the hypothesis that ordinary usage of common cosmetics as body lotions, skin creams, and ointments, often containing mineral oil, increase the risk for RA in the population in general. We cannot exclude, however, that these cosmetics can contribute to arthritis in individuals carrying certain genotypes or simultaneously being exposed to other arthritis-inducing environmental agents.