Early Rheumatoid Arthritis Study Research Articles

Risk of lung cancer in rheumatoid arthritis and in relation to autoantibody positivity and smoking

ObjectiveLung cancer is a common malignancy in rheumatoid arthritis (RA). Since smoking is a risk factor for both (seropositive) RA and lung cancer, it remains unclear whether RA, in itself,...

How do multiple long-term conditions impact on the cost-of-illness in early rheumatoid arthritis?

ObjectiveMultiple long-term conditions (MLTCs) are prevalent in rheumatoid arthritis (RA) and associated with worse outcomes and greater economic burden. However, little is known about the impact of MLTCs on the...

P198 The role of comorbidities alongside patient and disease characteristics on long-term disease activity in RA using UK inception cohort data

Abstract Background/Aims Control of disease activity in Rheumatoid Arthritis (RA) is crucial to prevent long-term joint damage and disability. European Alliance of Associations for Rheumatology (EULAR) guidelines recommend focus on disease activity when measuring health outcomes in people living with RA. Particularly, one of their four overarching principles targets clinical remission, defined as the absence of significant inflammatory disease activity, or low disease activity an acceptable alternative. In EULAR’s most recent guidelines (2014), attention was drawn to the role of comorbidities in RA disease management noting the “potential to preclude treatment intensification”. Besides this, recent work by the EULAR Task Force on difficult-to-treat RA recognises that comorbidities can influence the assessment of inflammatory activity in individuals with RA. This study aimed to identify early predictors of poor disease activity at five and 10 years, focussing on comorbidities alongside clinical/sociodemographic factors at first presentation. Methods Patients were recruited from two UK-based RA cohorts; Early Rheumatoid Arthritis Study (ERAS, 1986-2001) and Early Rheumatoid Arthritis Network (ERAN, 2002-2012). Participants were classified into two groups; low (<3.2) and moderate/high (≥3.2) Disease Activity Score (DAS28) at 5/10 years. Clinical information (e.g., rheumatoid nodules, erosions), sociodemographic factors (e.g., ethnicity, deprivation) and comorbidity burden (measured using the Rheumatic Diseases Comorbidity Index [RDCI]) were recorded at baseline and yearly thereafter. Multivariable logistic regression models (outcome; low versus DAS28≥3.2) were fitted using multiple imputation. Results 2,701 patients with RA were recruited (mean age 56.1 years, 66.9% female); 5-year follow-up data were available for 1,718 (63.4%) and 10-year for 820 (30.4%) patients. A higher proportion of individuals had DAS28≥3.2 values at 10 years than five (65.6% vs 59.7%). In multivariable analyses, baseline RDCI was not associated with DAS28 at five (OR 1.05, 95% CI 0.91 to 1.22) or 10 years (OR 0.99, 95% CI 0.75 to 1.31). Sociodemographic factors (female gender, worse deprivation) and poorer baseline HAQ were associated with DAS28≥3.2 at both timepoints, with no association found with age at onset. Being seropositive was associated with DAS28≥3.2 at 5 but not 10 years of follow-up. Conversely, a relationship existed between presence of erosions at baseline and 10-year DAS28 (OR 1.82, 95% CI 1.16 to 2.85). Conclusion This study found no association between baseline comorbidity burden and long-term RA disease activity. However, in models adjusted for comorbidity burden, associations with sociodemographic and clinical factors were demonstrated. These results build upon those relating to functional outcome and will accelerate the identification of those RA patients at increased risk of worse outcomes at initial rheumatology appointment. Additionally, these findings suggest that tailored intervention can be implemented in a timely manner, in line with national and international recommendations, potentially limiting permanent joint damage and disability to improve quality of life for individuals with RA. Disclosure A.D. Busby: None. J. Wason: None. A.G. Pratt: None. A. Young: None. J. Isaacs: None. E. Nikiphorou: None.

P203 Prevalence of lower limb disease activity and walking disability in the first two years of rheumatoid arthritis: results from the Scottish Early Rheumatoid Arthritis inception cohort

Abstract Background/Aims Lower limb synovitis and walking disability are reported as common in rheumatoid arthritis (RA), however there is a paucity of contemporary longitudinal studies reporting prevalence rates from disease onset. The aims of this study were to determine i) the prevalence of lower limb synovitis and walking disability from first presentation to 2 years, and ii) the prevalence of active foot/ankle disease amongst participants in Disease Activity Score-28 (DAS28)-remission. Methods The Scottish Early Rheumatoid Arthritis (SERA) study is an inception cohort of newly diagnosed inflammatory arthritis patients attending rheumatology units across Scotland. SERA data included demographics and 6-monthly clinical outcome data. Data from participants diagnosed with RA were included. Synovitis was determined using tender and swollen joint counts recorded at hips, knees, ankles and metatarsophalangeal (MTP) joints 2-5, and dichotomised as present (≥1) or absent (0). Walking disability was measured using the Health Assessment Questionnaire (HAQ) walking subscale (range 0-3) and dichotomised at present (≥1) or absent (0). Prevalence rates are expressed as percentages of participants. Subgroup analysis was performed to estimate the prevalence of foot/ankle joint swelling in participants who were in DAS28-remission (<2.6). Results A total of 932 participants (65.9% female) with a median (interquartile range [IQR]) age 59.5 years (49.5-68.1) were included, dropping to 391 at 2 years. Prevalence rates for lower limb synovitis and walking disability are reported in table 1. At 6 months, 138/816 (28.6%) participants met DAS28-remission criteria, followed by 124/691 (31.9%) at 1 year, 118/522 (39.2%) at 18 months, and 88/391 (39.5%) at 2 years. For those in DAS28-remission the prevalence of foot/ankle joint swelling was 10.3% at 6 months, 13.5% at 1 year, 17.6% at 18 months and 12% at 2 years. Conclusion Prevalence rates for knee, ankle and MTP joint swelling are initially high then stabilise, with largest reductions observed at 6 months. Joint tenderness prevalence rates follow a similar course but are consistently higher than joint swelling. Walking disability affects a significant proportion of patients throughout the first 2 years of RA. Clinically important rates of active foot/ankle disease are present amongst those classed in DAS28-remission. Disclosure N. Kelleher: None. G.J. Hendry: None.

Large joints are progressively involved in rheumatoid arthritis irrespective of rheumatoid factor status\u2014results from the early rheumatoid arthritis study

This study aimed to examine the progression of large joint involvement from early to established RA in terms of range of movement (ROM) and time to joint surgery, according to the presence of rheumatoid factor (RF). We used a historical longitudinal cohort of early RA patients. Patients were deemed RF negative if all repeated assessments were negative. The rate of progression from normal to any loss of range of movement (ROM) from years 3 to 14 were modelled using generalized estimating equations, for elbows, wrists, hips, knees and ankle, adjusting for confounders. Time to joint surgery was analysed using multivariable Cox models. A total of 1458 patients were included (66% female, mean age 55 years) and 74% were RF-positive. The prevalence of any loss of ROM, from year 3 through to 14 was highest in the wrist followed by ankle, knee, elbow and hip. Odds of loss of ROM increased over time in all joint regions assessed, at around 7–13% per year from year 3 to 14. Time to surgery was similar according to RF-status for the wrist and ankle, but RF-positive cases had a lower hazard of surgery at the elbow (HR 0.37, 0.15–0.90), hip (HR 0.69, 0.48–0.99) and after 10 years at the knee (HR 0.41, 0.25–0.68). Large joints become progressively involved in RA, most frequently affecting the wrist followed by ankle, which is overlooked in composite disease activity indices. RF-negative and positive cases progressed similarly. Treat-to-target approaches should be followed irrespective of RF status.

POS0530 HOW DOES MULTIMORBIDITY IMPACT ON THE DIRECT AND INDIRECT COSTS IN PATIENTS WITH RHEUMATOID ARTHRITIS?

Background:Comorbidities are prevalent in patients with rheumatoid arthritis (RA) and associated with worse outcomes as well as higher economic burden. Little is known about the impact of multimorbidity on the direct and indirect costs of RA. Evidence of the incremental scale of these multimorbidity costs will usefully inform RA interventions and policies.Objectives:The aim of this study was to describe how multimorbidity impacts on the cost-of-illness, including direct and indirect costs, in patients with RA.Methods:The Scottish Early Rheumatoid Arthritis (SERA) is a registry of patients newly presenting with RA since 2011. It contains data on patient characteristics, clinical outcomes, health-related quality of life, and employment status data. These data were linked to routinely recorded hospital admissions and primary care prescribing data. Direct costs were estimated by applying relevant unit costs to healthcare resource use quantities. Indirect cost estimates were obtained from information on employment status and hospital admissions, valued by age and sex specific wages. Two-part models (probit followed by generalized linear model) were used to estimate direct and indirect costs, adjusting for age, gender, and functional disability. The Charlson Comorbidity Index (CCI) score was calculated using patient ICD-10 diagnoses from hospital records. The number of comorbidities was categorized into “RA alone”, “single comorbidity” and “multimorbidity (>1 comorbidity)”.Results:Data were available for 1,150 patients, 65.7% were female and a mean age of 57.5±14 years. The majority of patients only had RA (54.1%), followed by a single comorbidity (23.4%) and multimorbidity (22.5%). Annual total costs were significantly higher for patients with multimorbidity (£6,669 95% CI £4,871-£8,466; OR 11.3 95% CI 8.14-15.87) and for patients with a single comorbidity (£2,075 95% CI £1,559-£2,591; OR 3.52 95% CI 2.61-4.79), when compared with RA alone (£590). The excess costs were mainly driven by direct costs (£6,281 versus £1,875 versus £556). Although the difference in indirect costs between patients with multimorbidity and a single comorbidity were not statistically significant (£1,218 versus £914, p=0.11), patients with multimorbidity were associated with significantly higher costs than those with RA only (£594, p<0.01).Conclusion:The presence of comorbidity contributes significant excess to both direct and indirect costs among RA patients. In particular, patients with multimorbidity incurred substantially higher direct costs than those with a single comorbidity or RA only.Acknowledgements:The study analysed the data from the Scottish Early Rheumatoid Arthritis (SERA) study with a linkage to routinely recorded health data from Information Service Division, National Service Scotland. We would like to thank all the patients, clinical and nursing colleagues who have contributed their time and support to the study, the SERA steering committee for the approval, and Allen Tervit from the Robertson Centre for Biostatistics, University of Glasgow for the timely technical supports.Disclosure of Interests:Ping-Hsuan Hsieh: None declared, Claudia Geue: None declared, Olivia Wu Consultant of: OW has received consultancy fees from Bayer, Lupin and Takeda outside the submitted work., Emma McIntosh: None declared

Factors associated with successful discontinuation of certolizumab pegol in early rheumatoid arthritis.

AimThe Certolizumab–Optimal Prevention of joint damage for Early Rheumatoid Arthritis (C‐OPERA) study demonstrated that in methotrexate (MTX)‐naïve early RA patients with poor prognostic factors, 1‐year certolizumab pegol (CZP) therapy added to the first year of 2‐year optimized MTX therapy brings radiographic and clinical benefits through 2 years even after stopping CZP. This exploratory analysis aimed to identify factors at baseline and at CZP discontinuation associated with successful CZP discontinuation.MethodsMTX‐naïve early RA patients with poor prognostic factors entered C‐OPERA (NCT01451203), a multicenter, randomized controlled trial. Patients were randomized to CZP + MTX (n = 159) or PBO + MTX (n = 157); those who completed the 1‐year, double‐blind period received MTX alone in Year 2 (CZP + MTX→MTX, n = 108; PBO + MTX→MTX, n = 71). Association between factors at baseline or at discontinuation of CZP and clinical/radiographic outcomes were evaluated by multiple logistic regression analysis. Predictive value cut‐offs were calculated using receiver operating characteristic analysis.ResultsSex (male) and low baseline Disease Activity Score of 28 joints – erythrocyte sedimentation rate (DAS28‐ESR) were associated with simple disease activity index (SDAI) remission (≤3.3), whereas high baseline DAS28‐ESR and modified total Sharp score (mTSS) were associated with clinically relevant radiographic progression (yearly progression mTSS > 3) at Week 104 (across both treatment arms). Low DAS28‐ESR (<2.1) and rheumatoid factor (RF; <74 IU/mL) at discontinuation of CZP were associated with SDAI remission at Week 104. At Week 104, SDAI remission was achieved by 75.0% (42/56) of patients with low DAS28‐ESR and RF at discontinuation, compared to 15.4% (2/13) of patients with high DAS28‐ESR and RF.ConclusionPatients with low RF and low disease activity after treatment with CZP + MTX may be able to discontinue CZP without risk of loss of response.

Secular changes in the progression of clinical markers and patient-reported outcomes in early rheumatoid arthritis

ObjectivesTo examine secular trends in the progression of clinical and patient-reported outcomes in early RA.MethodsA total of 2701 patients recruited to the Early Rheumatoid Arthritis Study or Early Rheumatoid Arthritis Network with year of diagnosis from 1986 to 2011. The 5-year progression rates for patients diagnosed at different points in time were modelled using mixed-effects regression; 1990, 2002 and 2010, were compared. Clinical markers of disease included the 28-joint count DAS and the ESR. Patient-reported markers included the HAQ, visual analogue scale of pain and global health, and the Short-Form 36.ResultsStatistically significant improvements in both 28-joint count DAS and ESR were seen over the 5 years in patients diagnosed with RA compared with those diagnosed earlier. By 5 years, 59% of patients with diagnosis in 2010 were estimated to reach low disease activity compared with 48% with diagnosis in 2002 and 32% with diagnosis in 1990. Whilst HAQ demonstrated statistically significant improvements, these improvements were small, with similar proportions of patients achieving HAQ scores of ≤1.0 by 5 years with a diagnosis in 1990 compared with 2010. Levels of the visual analogue scale and the Mental Component Scores of the Short-Form 36 indicated similar, statistically non-significant levels over the 5 years, irrespective of year diagnosed.ConclusionThis study demonstrates improvements in inflammatory markers over time in early RA, in line with improved treatment strategies. These have not translated into similar improvements in patient-reported outcomes relating to either physical or mental health.

Early Targeted Combination Treatment With Conventional Synthetic Disease-Modifying Antirheumatic Drugs and Long-Term Outcomes in Rheumatoid Arthritis: Ten-Year Follow-Up Results of a Randomized Clinical Trial.

The short-term outcomes of remission-targeted treatments of rheumatoid arthritis (RA) are well-established, but the long-term success of such strategies is speculative, as is the role of early add-on biologics. We assessed the 10-year outcomes of patients with early RA treated with initial remission-targeted triple combination of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), 7.5-mg prednisolone, and additional infliximab (IFX) or placebo infusions. Ninety-nine patients with early, DMARD-naive RA were treated with a triple combination of csDMARDs and prednisolone and randomized to double-blind receipt of infusions of either IFX (the Finnish Rheumatoid Arthritis Combination Therapy Trial [FIN-RACo] + IFX) or placebo (FIN-RACo + placebo) during the first 6 months. After 2 years, the treatment strategies became unrestricted, but the treatment goal was strict remission in the TNF-Blocking Therapy in Combination With Disease-Modifying Antirheumatic Drugs in Early Rheumatoid Arthritis (NEO-RACo) study. At 10 years, the clinical and radiographic outcomes and the drug treatments used between 5 and 10 years were assessed. Ninety patients (91%) were followed after 2 years, 43 in the FIN-RACo + IFX and 47 in the FIN-RACo + placebo group. At 10 years, the respective proportions of patients in strict NEO-RACo remission and in Disease Activity Score using 28 joints remission in the FIN-RACo + IFX and FIN-RACo + placebo groups were 46% and 38% (P = 0.46) and 82% and 72% (P = 0.29), respectively. The mean total Sharp/van der Heijde score was 9.8 in the FIN-RACo + IFX and 7.3 in the FIN-RACo + placebo group (P = 0.34). During the 10-year follow-up, 26% of the FIN-RACo + IFX group and 30% of the FIN-RACo + placebo group had received biologics (P = 0.74). In early RA, excellent results can be maintained up until 10 years in most patients treated with initial combination csDMARDs and remission-targeted strategy, regardless of initial IFX/placebo infusions.

Remission vs low disease activity: function, quality of life and structural outcomes in the Early Rheumatoid Arthritis Study and Network.

ObjectivesTo examine associations between function, quality of life and structural outcomes in patients achieving remission vs low disease activity in early RA.MethodsDemographic, clinical and radiographic variables were collected at baseline and then annually from the Early Rheumatoid Arthritis Study (ERAS) and Early Rheumatoid Arthritis Network (ERAN) inception cohorts in routine care from 1986 to 2012. Disease activity was categorized: mean DAS28 score between years 1 and 5: remission [mean remission DAS (mRDAS) <2.6] or low [mean low DAS (mLDAS) 2.6–3.2]; sustained low/remission DAS28 (sLDAS/sRDAS) at years 1 and 2; and sustained Boolean remission (sBR) at years 1 and 2. Changes in HAQ and Short Form 36 Health Survey Questionnaire [SF-36; physical (PCS) and mental (MCS) component score]) and total Sharp van der Heijde (SvdH) scores for each disease activity category were modelled using multi-level models. Covariates included year of onset, age, gender and DMARD use at first visit.ResultsOf 2701 patients, 562 (21%) were categorized mRDAS, 330 (12%) mLDAS, 279 (10%) sRDAS, 203 (7.5%) sLDAS and 93 (3%) sBR. Patients categorized as mRDAS had increasingly divergent improved HAQ, SF-36 PCS, MCS and total SvdH scores compared with mLDAS (P-values 0.001 to <0.0001, all time points). Patients categorized as sRDAS had better HAQ, SF-36 PCS and MCS scores (P-values 0.05 to <0.0001, all time points) and SvdH scores (P = 0.05, years 3–5) over sLDAS. sBR was associated with better HAQ, and SF-36 PCS and MCS scores over sLDAS (P-values 0.002 to <0.0001, all time points).ConclusionThese findings from routine care support ACR/EULAR guidelines that remission is a preferable goal over low disease activity in early RA.

A Swedish register-based, long-term inception cohort study of patients with rheumatoid arthritis - results of clinical relevance.

PurposeAt the end of the twentieth century, the outcome of rheumatoid arthritis (RA) was shown to be unsatisfactory and new therapeutic strategies were introduced. This initiated a register-based long-term study of early RA, the Better Anti-Rheumatic PharmacOTherapy (BARFOT) study. The aims were to evaluate the disease course and to acquire knowledge for improved care.Patients and methodsBARFOT is a multicentre observational study of patients with early RA, consecutively included 1992–2006. The patients are followed in daily practice according to a structured protocol for 15 years and data recorded in a web-based register. Also, through linkage of the BARFOT register to national registers we have acquired information on comorbidity and mortality.ResultsIn all, 2857 patients have been included and over 80 scientific articles have been published. Phenotypic characteristics at disease onset, i.e. gender, smoking habits and autoantibody profiles have been addressed. The disease course over 15 years was described. Early predictors for persistent disease activity, impaired function, joint damage and co-morbidities have been identified. Treatment strategies have been studied. A randomized sub-study gave strong support for the treatment of recent RA with low-dose prednisolone in combination with disease-modifying anti-rheumatic drug. Furthermore, the impact of lifestyle factors, such as smoking, alcohol consumption, body weight and physical activity has been addressed.ConclusionA register-based study like BARFOT has provided a basis for optimal long-term management of patients with RA. In addition, the register has made it possible to perform a diversity of studies of RA addressing various issues of major relevance to the patients.

Effectiveness of different combinations of DMARDs and glucocorticoid bridging in early rheumatoid arthritis: two-year results of CareRA.

To investigate whether MTX should be combined with an additional DMARD and bridging glucocorticoids as initial treatment for patients with early RA to induce an effective long-term response. The Care in early RA study is a two-year investigator-initiated pragmatic multicentre randomized trial. Early RA patients, naïve to DMARDs and glucocorticoids, were stratified based on prognostic factors. High-risk patients were randomized to COBRA-Classic (n = 98): MTX, sulfasalazine, prednisone step-down from 60 mg; COBRA-Slim (n = 98): MTX, prednisone step-down from 30 mg; or COBRA-Avant-Garde (n = 93): MTX, leflunomide, prednisone step-down from 30 mg. Low-risk patients were randomized to COBRA-Slim (n = 43); or Tight Step Up (TSU) (n = 47): MTX without prednisone. Clinical/radiological outcomes at year 2, sustainability of response, safety and treatment adaptations were assessed. In the high-risk group 71/98 (72%) patients achieved a DAS28-CRP < 2.6 with COBRA-Slim compared with 64/98 (65%) with COBRA-Classic and 69/93 (74%) with COBRA-Avant-Garde (P = 1.00). Other clinical/radiological outcomes and sustainability of response were similar. COBRA-Slim treatment resulted in less therapy-related adverse events compared with COBRA-Classic (P = 0.02) or COBRA-Avant-Garde (P = 0.005). In the low-risk group, 29/43 (67%) patients on COBRA-Slim and 34/47 (72%) on TSU achieved a DAS28-CRP < 2.6 (P = 1.00). On COBRA-Slim, low-risk patients had lower longitudinal DAS28-CRP scores over 2 years, a lower need for glucocorticoid injections and a comparable safety profile compared with TSU. All regimens combining DMARDs with glucocorticoids were effective for patients with early RA up to 2 years. The COBRA-Slim regimen, MTX monotherapy with glucocorticoid bridging, provided the best balance between efficacy and safety, irrespective of patients' prognosis. ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT01172639.

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...

Normal mortality of the COBRA early rheumatoid arthritis trial cohort after 23 years of follow-up

ObjectivesMortality in patients with rheumatoid arthritis (RA) is higher than in the general population. We investigated mortality in the COBRA-trial cohort after 23 years follow-up, compared with a reference sample...

Validation of methods for converting the original Disease Activity Score (DAS) to the DAS28

The Disease Activity Score (DAS) is integral in tailoring the clinical management of rheumatoid arthritis (RA) patients and is an important measure in clinical research. Different versions have been developed over the years to improve reliability and ease of use. Combining the original DAS and the newer DAS28 data in both contemporary and historical studies is important for both primary and secondary data analyses. As such, a methodologically robust means of converting the old DAS to the new DAS28 measure would be invaluable. Using data from The Early RA Study (ERAS), a sub-sample of patients with both DAS and DAS28 data were used to develop new regression imputation formulas using the total DAS score (univariate), and using the separate components of the DAS score (multivariate). DAS were transformed to DAS28 using an existing formula quoted in the literature, and the newly developed formulas. Bland and Altman plots were used to compare the transformed DAS with the recorded DAS28 to ascertain levels of agreement. The current transformation formula tended to overestimate the true DAS28 score, particularly at the higher end of the scale. A formula which uses all separate components of the DAS was found to estimate the scores with a higher level of precision. A new formula is proposed that can be used by other early RA cohorts to convert the original DAS to DAS28.

The association of obesity with disease activity, functional ability and quality of life in early rheumatoid arthritis: data from the Early Rheumatoid Arthritis Study/Early Rheumatoid Arthritis Network UK prospective cohorts.

To examine associations between BMI and disease activity, functional ability and quality of life in RA. Data from two consecutive, similarly designed UK multicentre RA inception cohorts were used: the Early RA Study (ERAS) and the Early RA Network (ERAN). Recruitment figures/median follow-up for the ERAS and ERAN were 1465/10 years (maximum 25 years), and 1236/6 years (maximum 10 years), respectively. Standard demographic and clinical variables were recorded at baseline and annually. Multilevel piecewise longitudinal models with a change point at 2 years were used with the 28-joint DAS (DAS28), ESR, HAQ and 36-item Short Form Health Survey (SF-36) physical (PCS) and mental (MCS) components as dependent variables. BMI was examined in separate models as both continuous and categorical variables (based on World Health Organization definitions) and up to 5 years from disease onset. BMI data from 2386 newly diagnosed RA patients (11 348 measures) showed an increase in BMI of 0.27 U annually (95% CI 0.21, 0.33). Baseline obesity was associated with a significant reduction in the odds of achieving a low year 2 DAS28 [OR 0.52 (95% CI 0.41, 0.650)]. At year 2, HAQ and SF-36 PCS scores were significantly worse but not at year 5 in patients obese at baseline. Obesity at year 2 was associated with higher DAS28 scores at year 2, but not at year 5, and also associated with significantly higher HAQ and SF-36 PCS scores at years 2 and 5. Obesity prevalence is rising in early RA and associates with worse disease activity, function and health-related quality of life, with a significant negative impact on achieving a low DAS28. The data argue strongly for obesity management to become central to treatment strategies in RA.

A 4-year non-randomized comparative phase-IV study of early rheumatoid arthritis: integrative anthroposophic medicine for patients with preference against DMARDs versus conventional therapy including DMARDs for patients without preference

BackgroundWhile disease-modifying antirheumatic drugs (DMARDs) are a mainstay of therapy for rheumatoid arthritis (RA), some patients with early RA refuse DMARDs. In anthroposophic medicine (AM), a treatment strategy for early RA without DMARDs has been developed. Preliminary data suggest that RA symptoms and inflammatory markers can be reduced under AM, without DMARDs.Patients and methodsTwo hundred and fifty-one self-selected patients aged 16–70 years, starting treatment for RA of <3 years duration, without prior DMARD therapy, participated in a prospective, non-randomized, comparative Phase IV study. C-patients were treated in clinics offering conventional therapy including DMARDs, while A-patients had chosen treatment in anthroposophic clinics, without DMARDs. Both groups received corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). Primary outcomes were intensity of RA symptoms measured by self-rating on visual analog scales, C-reactive protein, radiological progression, study withdrawals, serious adverse events (SAE), and adverse drug reactions in months 0–48.ResultsThe groups were similar in most baseline characteristics, while A-patients had longer disease duration (mean 15.1 vs 10.8 months, p<0.0001), slightly more bone destruction, and a much higher proportion of women (94.6% vs 69.7%, p<0.0001). In months 0–12, corticosteroids were used by 45.7% and 81.6% (p<0.0001) and NSAIDs by 52.8% and 68.5% (p=0.0191) of A- and C-patients, respectively. During follow-up, both groups not only had marked reduction of RA symptoms and C-reactive protein, but also some radiological disease progression. Also, 6.2% of A-patients needed DMARDs. Apart from adverse drug reactions (50.4% and 69.7% of A- and C-patients, respectively, p=0.0020), none of the primary outcomes showed any significant between-group difference.ConclusionStudy results suggest that for most patients preferring anthroposophic treatment, satisfactory results can be achieved without use of DMARDs and with less use of corticosteroids and NSAIDs than in conventional care.LimitationBecause of the non-randomized study design, with A-patients choosing anthroposophic treatment, one cannot infer how this treatment would have worked for C-patients.

Reductions in Radiographic Progression in Early Rheumatoid Arthritis Over Twenty-Five Years: Changing Contribution From Rheumatoid Factor in Two Multicenter UK Inception Cohorts.

To assess the 5-year progression of erosions and joint space narrowing (JSN) and their associations with rheumatoid factor (RF) status in 2 large, multicenter, early rheumatoid arthritis cohorts, spanning 25 years. Radiographic joint damage was recorded using the Sharp/van der Heijde (SHS) method in the Early Rheumatoid Arthritis Study (ERAS), 1986-2001, and the Early Rheumatoid Arthritis Network (ERAN), 2002-2013. Mixed-effects negative binomial regression estimated changes in radiographic damage over 5 years, including erosions and JSN, separately. RF, along with age, sex, and baseline markers of disease activity were controlled for. A total of 1,216 patients from ERAS and 446 from ERAN had radiographic data. Compared to ERAS, ERAN patients had a lower mean total SHS score at baseline (ERAN 6.2 versus ERAS 10.5; P < 0.001) and mean annual rate of change (ERAN 2.5 per year versus ERAS 6.9 per year; P < 0.001). Seventy-four percent of ERAS and 27% of ERAN patients progressed ≥5 units. Lower scores at baseline in ERAN were largely driven by reductions in JSN (ERAS 3.9 versus ERAN 1.2; P < 0.001), along with erosions (ERAS 1.9 versus ERAN 0.8; P < 0.001). RF was associated with greater progression in each cohort, but the absolute difference in mean annual rate of change for RF-positive patients was substantially higher for ERAS (RF positive 8.6 versus RF negative 5.1; P < 0.001), relative to ERAN (RF positive 2.0 versus RF negative 1.9; P = 0.855). Radiographic progression was shown to be significantly reduced between the 2 cohorts, and was associated with lower baseline damage and other factors, including changes in early disease-modifying antirheumatic drug use. The impact of RF status as a prognostic marker of clinically meaningful change in radiographic progression has markedly diminished in the context of more modern treatment.

Secular Changes in Clinical Features at Presentation of Rheumatoid Arthritis: Increase in Comorbidity But Improved Inflammatory States.

To examine secular trends in demographics, clinical manifestations, and comorbidity on first presentation of rheumatoid arthritis (RA) prior to disease-modifying antirheumatic drug treatment. A total of 2,701 patients were recruited over 25 years to 2 UK-based RA inception cohorts: the Early Rheumatoid Arthritis Study (9 centers; 1986-2001) and the Early Rheumatoid Arthritis Network (23 centers; 2002-2012). Trends in demographic and baseline clinical/laboratory and radiographic variables and comorbidities were estimated using mixed-effects models, including random effects for recruitment center. Age at onset increased from 53.2 to 57.7 years in 1990 and 2010, respectively (2.6 months/year; 95% confidence interval [95% CI] 1.2, 4.1). Sex ratio, the proportion living in deprived areas, and smoking status were unchanged (P > 0.05) and there were no changes in the proportion seropositive or erosive at baseline (P > 0.05). After controlling for treatment at the time of assessment, erythrocyte sedimentation rate decreased and hemoglobin increased over time (P > 0.05); however, the Health Assessment Questionnaire (HAQ), the Disease Activity Score (DAS), the DAS in 28 joints, and joint counts were unchanged (P > 0.05). The overall prevalence of comorbidity increased from 29.0% in 1990 to 50.7% in 2010, mainly due to cardiovascular and non-cardiac vascular conditions, including hypertension. There was a significant increase in body mass index (0.15 units/year; 95% CI 0.11, 0.18), resulting in an increase in the prevalence of obesity from 13.3% in 1990 to 33.6% in 2010. Age at onset and comorbidity burden, especially obesity, have increased at RA presentation over 25 years, reflecting wider demographic trends at the population level. In contrast, there were no accompanying changes in disease severity assessed by composite markers of disease activity, radiographic erosions, seropositivity, or HAQ at presentation. Treatment strategies in early RA should take greater account of the impact of comorbidity on outcomes.

The Scottish Early Rheumatoid Arthritis (SERA) Study: an inception cohort and biobank.

BackgroundThe Scottish Early Rheumatoid Arthritis (SERA) study is an inception cohort of rheumatoid (RA) and undifferentiated arthritis (UA) patients that aims to provide a contemporary description of phenotype and outcome and facilitate discovery of phenotypic and prognostic biomarkersMethodsDemographic and clinical outcome data are collected from newly diagnosed RA/UA patients every 6 months from around Scotland. Health service utilization data is acquired from Information Services Division, NHS National Services Scotland. Plain radiographs of hands and feet are collected at baseline and 12 months. Additional samples of whole blood, plasma, serum and filtered urine are collected at baseline, 6 and 12 monthsResultsResults are available for 1073 patients; at baseline, 76 % were classified as RA and 24 % as UA. Median time from onset to first review was 163 days (IQR97-323). Methotrexate was first-line DMARD for 75 % patients. Disease activity, functional ability and health-related quality of life improved significantly between baseline and 24 months, however the proportion in any employment fell (51 to 38 %, p = 0.0005). 24 % patients reported symptoms of anxiety and/or depression at baseline. 35/391 (9 %) patients exhibited rapid radiographic progression after 12 months. The SERA Biobank has accrued 60,612 samplesConclusionsIn routine care, newly diagnosed RA/UA patients experience significant improvements in disease activity, functional ability and health-related quality of life but have high rates of psychiatric symptoms and declining employment rates. The co-existence of a multi-domain description of phenotype and a comprehensive biobank will facilitate multi-platform translational research to identify predictive markers of phenotype and prognosisElectronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-1318-y) contains supplementary material, which is available to authorized users.