Management Of Early Rheumatoid Arthritis Research Articles

O07 The increase in erythrocyte mean corpuscular volume by methotrexate is potentiated by hydroxychloroquine and is an early indicator of clinical response in rheumatoid arthritis

Background/Aims Rheumatologists are facing a significant challenge in the management of early rheumatoid arthritis (RA) due to limitations placed on outpatient visits during the COVID-19 pandemic. Frequent clinical assessments of disease activity are recommended during implementation of the treat to target strategy to achieve remission. A biomarker indicating response to methotrexate during the early phase of therapy could complement clinical examination. Methotrexate increases erythrocyte mean corpuscular volume (MCV), which is measured routinely, prompting us to investigate whether changes in MCV could act as an early indicator of response. Methods Patients with early RA who were started on methotrexate therapy were included from two independent cohorts. The larger cohort (discovery cohort, n = 655) was used to build the model and the second cohort (validation cohort, n = 225) was applied to test the prediction of the model. Conventional statistical, and machine learning approaches were adopted to identify key determinants that influence the potential relationship between MCV and clinical response, defined as attainment of remission or low disease activity, at six months after starting methotrexate. Results A LASSO penalised logistic regression model was built with the discovery cohort [area under the receiver operating characteristics (AUROC) curve = 0.76], where change of MCV from three months [Odds ratio (OR) 1.53 (95% CI 1.38-1.70)], concomitant use of hydroxychloroquine [OR 2.16 (95% CI 1.52 - 3.07, p < 0.001)], and seropositivity [OR 1.83 (95% CI 1.12 - 3.03, p = 0.02)] were associated with favourable methotrexate response [accuracy 81% (95% CI 76%-86%) of the model testing against discovery model]. Different machine learning classification methods were applied. Random forest exhibited the maximum accuracy and AUROC (89%, and 86%, respectively), confirming the above three predictors as the most significant. Two latent classes (class 1: smaller MCV increase and class 2: greater MCV increase) were identified based on the MCV changes over six months. Class 1 had fewer responders and a lower number of patients on hydroxychloroquine compared to class 2. The earliest time point of significant difference of MCV between responders and non-responders was three months [mean difference 1.43 (95% CI 0.57-2.3)]. Combination hydroxychloroquine and methotrexate caused the greatest increase in MCV with a difference between responders and non-responders at 2 months. Change of MCV at three months showed AUROC of 0.75 to predict treatment response to the combination of methotrexate and hydroxychloroquine at six months with an optimal cut-point of MCV 3.5 fL (95% CI 3.5-3.6) with 71% sensitivity and 75%, specificity. Conclusion Our data provides mechanistic insight into the synergistic clinical benefit of concomitant hydroxychloroquine with methotrexate, boosting the rise in erythrocyte MCV which could serve as an early biomarker of treatment response. Disclosure M.R. Shipa: Grants/research support; Versus arthritis. S. Yeoh: Grants/research support; Royal College of Physicians, Rosetrees Trust, NIHR University College London Hospitals Biomedical Research Centre, UCLH Charities. A. Embleton-Thirsk: None. D. Mukerjee: None. M.R. Ehrenstein: Grants/research support; University College London Hospital Biomedical Research Centre.

Value of MRI and ultrasound for prediction of therapeutic response and erosive progression in patients with early rheumatoid arthritis managed by an aggressive treat-to-target strategy

ObjectivesTo investigate if inflammation detected by MRI or ultrasound at rheumatoid arthritis (RA) onset is predictive of erosive progression or poor response to methotrexate monotherapy, and to investigate if subclinical...

P229 The impact of early RA on lower limb kinematics

Abstract Background Despite advancements in the pharmacological management of early rheumatoid arthritis (RA), walking impairments remain a key feature of this disease. With limited published research analysing the impact of early RA on lower limb movement patterns during gait, more comprehensive data are required to optimise the recognition and targeted management of early musculoskeletal pathology in RA. This study compared lower limb biomechanical function in early RA participants to age and gender-matched healthy controls, determining explanatory relationships with measures of disease activity and physical function. Methods In a cross-sectional study using three-dimensional (3D) motion capture, lower limb kinematic data from 18 RA participants with disease duration ≤ 2 years were compared to 18 adults matched for age and gender. Standard clinical measures were used to collect data on disease activity, rheumatology physical function and self-reported physical impairment. Between-group differences in lower limb kinematics were investigated using principal component analysis (PCA). Explanatory variables of significantly altered lower limb kinematics in early RA were investigated using linear regression analysis. Results Of the lower limb parameters analysed, eversion of the rearfoot and midfoot were found to be significantly increased (p &amp;lt; 0.05) in early RA, with two principal components explaining 91.94% and 97.57% of the respective between-group variance. Rearfoot motion in early RA was explained by single regression models incorporating walking speed (R2 of 0.456, F ratio = 12.585, p = &amp;lt; 0.003), the footwear/impairment domain of the Leeds Foot Impact Scale (R2 = 0.358, F ratio = 8.371, p = &amp;lt;0.011) and rheumatoid factor (R2 = 0.358, F ratio = 8.371, p = &amp;lt;0.011). Midfoot eversion was explained by single regression models incorporating the timed walk test (R2 = 0.372, F ratio = 4.507, p = &amp;lt; 0.031), the percentage of gait at which toe-off occurred (R2 of 0.253, F ratio = 5.425, p = &amp;lt; 0.033) and walking speed (R2 = 0.235, F ratio = 4.912, p = &amp;lt; 0.042). Abduction of the rearfoot and midfoot were also significantly increased (p &amp;lt; 0.05) in early RA. Two principal components explained 97.67% and 97.2% of the respective between-group variance observed. No variables were found to explain altered motion at these sites. Dorsiflexion at the first metatarsophalangeal joint (MPJ) was significantly reduced (p &amp;lt; 0.05) in early RA, with a single principal component explaining 97.43% of between-group variance which was explained by a single regression model incorporating step length (R2 = 0.372, F ratio = 4.507, p = &amp;lt;0.031). Conclusion Within two years following diagnosis of RA, significant alterations in foot kinematics were observed despite management using current treat to target protocols. These alterations were of a greater magnitude than previously reported and were largely independent of current measures of disease activity, physical function and disease impact. Disclosures A.G. Izod Grants/research support; Dr William Scholl Research and Develpment Fund. C. Bowen None. K. Gallagher None. M. Seed None.

Clinical characteristics associated with drug-free sustained remission in patients with rheumatoid arthritis: Data from Korean Intensive Management of Early Rheumatoid Arthritis (KIMERA)

ObjectivesThere is limited information on treatment withdrawal in patients with rheumatoid arthritis (RA). This study investigated the clinical course after stopping disease-modifying anti-rheumatic drugs (DMARDs) in patients with well-controlled RA and the clinical features associated with disease flare. MethodsAmong patients in the Korean Intensive Management of Early Rheumatoid Arthritis (KIMERA) cohort, discontinuation of DMARDs was determined by a shared decision between patient and rheumatologist. Drug-free remission was defined as (1) non-use of DMARDs and corticosteroids, (2) Disease Activity Score in 28 joints (DAS28) <2.6, and (3) no evidence of synovitis. The maintenance rate of drug-free remission and the predictors for flare were evaluated using Cox proportional hazard models. ResultsOf 234 patients, 50 patients discontinued DMARDs. All but one using etanercept were treated with conventional synthetic DMARDs. The median follow-up duration was 30 months, and 31 patients (62%) experienced disease flare after stopping DMARDs. The maintenance rate of drug-free remission was 94.0%, 86.7%, and 46.1% at 12, 24, and 48 months, respectively. Disease flare was correlated with longer time to remission, failure of initial DMARDs, and longer duration of disease and higher disease activity at DMARD withdrawal (P = 0.001, 0.022, 0.010 and 0.037, respectively). In multivariate analyses, longer duration of disease (>24 months) and higher disease activity (DAS28 >2.26) at DMARD withdrawal was independently associated with disease flare. ConclusionDrug-free remission was feasible in selected patients with well-controlled RA. Patients with early RA and lower disease activity at DMARD withdrawal are more likely to maintain the drug-free remission.

The first national clinical audit for rheumatoid arthritis.

The first national audit for rheumatoid and early inflammatory arthritis has benchmarked care for the first 3 months of follow-up activity from first presentation to a rheumatology service. Access to care, management of early rheumatoid arthritis and support for self care were measured against National Institute for Health and Care Excellence quality standards; impact of early arthritis and experience of care were measured using patient-reported outcome and experience measures. The results demonstrate delays in referral and accessing specialist care and the need for service improvement in treating to target, suppression of high levels of disease activity and support for self-care. Improvements in patient-reported outcomes within 3 months and high levels of overall satisfaction were reported but these results were affected by low response rates. This article presents a summary of the national data from the audit and discusses the implications for nursing practice.

Epidemiological evaluation quality of life in patients suffering from early rheumatoid arthritis: a pragmatic, prospective, randomized, blind allocation controlled of a modular program group intervention.

OBJECTIVES:Epidemiology has taken on new roles in the management of health care services. In this study, we developed a non-pharmacological self-management modular program group intervention and evaluated its efficacy as an adjunct therapy in patients suffering from early rheumatoid arthritis (RA).METHODS:Patients were randomized to either participate in a non-equivalent intervention group along with the standard of care or only receive standard-of-care treatment at a community rheumatology center. The outcomes measured were a pain visual analog scale (VAS), patient general health (GH) on a VAS, and the Short Form 36 Health Survey version 2 scale measuring quality of life. These parameters were evaluated in the first week to obtain baseline values, and at 20, 32, 48, and 60 weeks to evaluate the efficacy of the intervention group.RESULTS:The patients were randomized, with 100 patients in the intervention group and 106 in the control group. The intervention and control groups were similar with regard to the percentage of women (86% vs. 89.6%), tobacco usage (25% vs. 19.8%), mean age (42.6±13.2 years vs. 46.6±10.9 years), and disease duration (15.3±6.7 months vs. 14.5±6.6 months). The mean outcomes were significantly different between the two groups, and post-hoc pairwise analysis demonstrated significant deterioration in the control group in contrast to improvement in the intervention group at the second, third, fourth, and fifth evaluations. Improvements were often seen as early as the 12-week and 24-week follow-up visits.CONCLUSIONS:Epidemiology contributes to the evaluation of how well specific therapies or other health interventions prevent or control health problems. The modular program group intervention implemented in this study appears to be a suitable and feasible method to facilitate much more comprehensive management of early RA in socioeconomically challenged communities.

A general practice perspective on early rheumatoid arthritis management: A qualitative study from Flanders

ABSTRACTBackground: General practitioners (GPs) may play a crucial role in early recognition, rapid referral and intensive treatment follow-up of patients with rheumatoid arthritis (RA). To improve early RA management, perceived barriers in general practice must be addressed. However, the general practice perspective on early RA management remains understudied.Objective: To explore GPs’ experiences, beliefs and attitudes regarding detection, referral, and intensive treatment for early RA.Methods: In 2014, a qualitative study was conducted by means of individual, in depth, face-to-face interviews of a purposive sample of 13 Flemish GPs. Interviews were audio-recorded, transcribed verbatim and coded using the constant comparative method.Results: GPs applied multiple assessment techniques for early RA detection and regularly prescribed non-steroidal anti-inflammatory drugs if they suspected early RA. However, GPs felt unconfident about their detection skills because early RA symptoms are often unclear, diagnostic tests could provide inconclusive results and the incidence is low in general practice. GPs mentioned various approaches and multiple factors determining their referral decision. Perceived referral barriers included limited availability of rheumatology services and long waiting times. GPs considered intensive treatment initiation to be the expertise of rheumatologists. Reported key barriers to intensive treatment included patients’ resistance and non-adherence, lack of GP involvement and unsatisfactory collaboration with rheumatology services.Conclusion: GPs acknowledge the importance of an early and intensive treatment, but experience various barriers in the management of early RA. GPs should enhance their skills to detect early RA and should actively be involved in early RA care.

Are illness perception and coping style associated with the delay between symptom onset and the first general practitioner consultation in early rheumatoid arthritis management? An exploratory study within the CareRA trial

Objectives: Persons who are later diagnosed with early rheumatoid arthritis (ERA) often delay their first contact with a health professional after symptom onset. Besides initial symptoms, psychosocial characteristics of individuals may influence their help-seeking behaviour. We explored the role of disease characteristics, illness perception, and coping in patient-related delay before treatment initiation in recently diagnosed patients with ERA.Method: This exploratory, cross-sectional study included 112 patients with ERA from the Care for early RA (CareRA) trial for whom complete data on patient-related delay, coping, and illness perception were available. In addition to baseline sociodemographic and clinical data, the patients’ psychosocial profiles were assessed with the Utrecht Coping List (UCL) and the revised Illness Perception Questionnaire (IPQ-R). Correlations were measured by Spearman’s rho. Using regression analyses, we weighted the association of variables with patient-related delay.Results: Patient-related delay was positively correlated with perceptions of causality including psychological attributions (r = 0.301, p = 0.001), risk factors (r = 0.189, p = 0.045), immunity (r = 0.261, p = 0.005), and passive coping (r = 0.222, p = 0.018). It was negatively correlated with the 28 swollen joint count (SJC28; r = −0.194, p = 0.040), perceptions of treatment control (r = −0.271, p = 0.004), and illness coherence (r = −0.208, p = 0.028). Clinical and psychosocial variables explained 15% and 18%, respectively, of the variability in patient-related delay.Conclusions: Aside from a lower SJC, a longer patient-related delay was correlated with a passive coping style, a strong conviction of symptom causality, poor expected treatment control, and a feeling of limited illness coherence. Psychosocial aspects influence individuals’ help-seeking behaviour and are worth considering when aiming for a reduction in ERA treatment delay.

Can the publication of guidelines change the management of early rheumatoid arthritis? An interrupted time series analysis from the United Kingdom.

To assess whether publication of national treatment guidelines improved the management of early RA in the UK. Incident diagnoses of RA in persons aged over 18 years from 1995 to 2010 were identified from the Clinical Practice Research Datalink. Using a natural experimental study design, interrupted time series analysis was used to assess whether trends in the proportion of patients receiving DMARDs, within 3 and 12 months of diagnosis, changed following publication of British Society for Rheumatology guidelines in 2006. Between 1995 and 2010, 11 772 incident cases of RA were identified. There was a progressive increase in the proportion of patients prescribed any DMARD within 12 months from 43.3% in 1995 to 78.5% in 2010. After publication of the British Society for Rheumatology guidelines, the proportion of patients prescribed any DMARD within 12 months increased by 4.2% (P = 0.053). Prior to the guidance, prescribing was increasing by 1.64% per year, compared with 3.55% per year after publication (P < 0.001). Guidelines published by a national body can improve the proportion of patients receiving DMARD treatment in the first year after diagnosis of RA.

Hypovitaminosis D in recent onset rheumatoid arthritis is predictive of reduced response to treatment and increased disease activity: a 12month follow-up study.

BackgroundVitamin D displays immunomodulatory activities and has been proposed as a potential player in the pathogenesis of rheumatoid arthritis (RA). A negative association between serum 25(OH) vitamin D levels and RA activity was demonstrated but longitudinal studies investigating the role of vitamin D levels in predicting RA activity and response to treatment are lacking. Therefore, this study was designed to test the hypothesis of an association between serum 25(OH) vitamin D levels at RA diagnosis and disease activity evaluated by clinimetric, laboratory and ultrasound (US) parameters and to detect the prevalence of remission and response to treatment after 12 months follow-up.MethodsThis is a longitudinal, retrospective study on data obtained from thirty-seven patients with early RA treatment-naïve. Serum inflammatory markers, auto-antibodies and 25(OH) vitamin D levels were obtained at baseline. Hypovitaminosis D was diagnosed for 25(OH) vitamin D levels < 20 ng/ml. Tender joint count (TJCs), swollen joint count (SJCs), Visual Analog Scales (VAS), Disease Activity Score (DAS) 28 score were assessed at baseline and 12 months after diagnosis. Joints synovitis and power-Doppler were evaluated at baseline and 12 months later.ResultsAt baseline mean 25(OH) vitamin D levels were 24.4 ± 11.9 ng/ml; 35% of study subjects had hypovitaminosis D which strongly associated with higher RA activity and lower prevalence of remission and response to treatment (all p-values < 0.001). The percentage of patients not presenting a reduction of the US synovitis score after 12 months from diagnosis was significantly higher among patients with hypovitaminosis D than in those with normal serum 25(OH) vitamin D at baseline.ConclusionsIn patients with early RA and basal hypovitaminosis D after 12 months follow-up reduction of disease activity and percentage of remission and response to treatment were significantly lower than those observed in patients with normal vitamin D levels. These results provide further support to the immunomodulatory action of vitamin D in RA and suggest a role of basal vitamin D status in the prediction of disease evolution. Vitamin D measurement and possibly vitamin D supplementation should be considered an additional option in the management of early RA patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-015-0505-6) contains supplementary material, which is available to authorized users.

Glucocorticoids in Early Rheumatoid Arthritis: Are the Benefits of Joint-Sparing Effects Offset by the Adverse Effect of Osteoporosis? The Effects on Bone in the Utrecht Study and the CAMERA-II Study

This paper reviews the clinical effects on bone of 10 mg of prednisone daily in early rheumatoid arthritis, given for 2 years in the Utrecht Study and in the second CAMERA (Computer- Assisted Management in Early Rheumatoid Arthritis) Study, and addresses the question whether there were joint-sparing effects and whether these were offset by adverse effects, especially osteoporosis. We conclude that a 2-year adjunct treatment with 10 mg of prednisone daily increases the benefits of disease-modifying antirheumatic drug therapy and has joint-sparing properties, even if added to the tight control methotrexate-based strategy aiming for remission. Importantly, with good control of inflammation and adequate use of calcium, vitamin D and bisphosphonates - according to national or international guidelines - steroid-induced osteoporosis is rare over 2 years.

SAT0088 Economic Evaluation of A Tight-Control Treatment Strategy Using an Imaging Device (HANDSCAN) for Monitoring Joint Inflammation in Early Rheumatoid Arthritis

BackgroundNowadays treat-to-target by means of tight-control is generally accepted as the standard treatment principle in early rheumatoid arthritis (RA) (Schoels et.al.). However, this requires frequent (monthly) visits including comprehensive clinical...

SAT0042 Comparison between Two Clinical Pathways for the Management of Early Rheumatoid Arthritis: Routine Care versus Early Arthritis Clinic

BackgroundThere is no doubt that the Early Arthritis Clinic (EAC) institution has provided a better awareness about early arthritis (EA) in term of potential evolution in Rheumatoid Arthritis (RA). However,...

Glucocorticoids in the treatment of rheumatoid arthritis: still used after 65 years

Glucocorticoids (GCs) have been used for over 65 years in the treatment of rheumatoid arthritis (RA). There is by now good evidence for their disease-modifying effects, especially in early RA. When used in a dosage of 5-10 mg, most adverse effects can adequately be monitored, though accurate monitoring and awareness for infections are important. In this paper, the Utrecht and computer-assisted management in early rheumatoid arthritis (CAMERA) studies are discussed; the Utrecht study was the first of these studies in which 10 mg prednisone daily was compared to placebo in patients with early RA. A clear disease-modifying effect was shown. In the CAMERA II study, patients with early RA were treated with a tight-control scheme of climbing dosages of methotrexate plus either 10 mg prednisone daily or placebo. After 2 years, 70% of the patients treated with a tight-control strategy without GCs had no erosions versus 82% of the patients treated with additional prednisone. Remission was reached more often and earlier on in the strategy with prednisone compared to the strategy with placebo.

Five-year Favorable Outcome of Patients with Early Rheumatoid Arthritis in the 2000s: Data from the ESPOIR Cohort

To report the 5-year outcome of a large prospective cohort of patients with very early rheumatoid arthritis (RA), and to identify factors predictive of outcome. Patients were recruited if they had early arthritis of < 6 months' duration, had a high probability of developing RA, and had never been prescribed disease-modifying antirheumatic drugs (DMARD) or steroids. Logistic regression analysis was used to determine factors that predict outcome. We included 813 patients from December 2002 to April 2005. Age was 48.1 ± 12.6 years, delay before referral 103.1 ± 52.4 days, 28-joint Disease Activity Score (DAS28) 5.1 ± 1.3, Health Assessment Questionnaire (HAQ) 1.0 ± 0.7; 45.8% and 38.7% had rheumatoid factor or antibodies to cyclic citrullinated peptide (anti-CCP), respectively; 22% had hand or foot erosions; 78.5% fulfilled the American College of Rheumatology/European League Against Rheumatism criteria for RA at baseline and 93.8% during followup. At 5 years, 573 patients were evaluated. The outcome was mild for most patients: disease activity (median DAS28 = 2.5) and HAQ disability (median 0.3) were well controlled over time; 50.6% achieved DAS28 remission and 64.7% low disease activity. Radiographic progression was low (2.9 Sharp unit/year) and only a few patients required joint surgery. Nevertheless, some patients developed new comorbidities. During the 5 years, 82.7% of patients had received at least 1 DMARD (methotrexate, 65.9%), 18.3% a biological DMARD, and about 60% prednisone at least once. Anti-CCP was the best predictor of remaining in the cohort for 5 years, of prescription of synthetic or biologic DMARD, and of radiographic progression. The 5-year outcome of an early RA cohort in the 2000s was described. Anti-CCP was a robust predictor of outcome. The generally good 5-year outcome could be related to early referral and early effective treatment, key processes in the management of early RA in daily practice.

Rheumatoid Arthritis

0.5% to 0.8% of all adults suffer from rheumatoid arthritis (RA). The main considerations for persons with new-onset RA are early diagnosis, disease-modifying anti-rheumatic drugs (DMARDs), remission, and interdisciplinary treatment. As part of the process of creating a new S3 guideline on the management of early RA and a new S1 guideline on stage-adapted pharmacotherapy for RA, the authors conducted a selective search and review of the literature and specifically updated it to 20 March 2013. In patients presenting with joint inflammation, the diagnosis of RA can be directly confirmed (positive predictive value, 85% to 97%), and its prognosis assessed, on the basis of the following findings: joint examination, acute phase reaction, serology (rheumatoid factor [RF], antibody against citrullinated peptides/proteins [ACPA], and duration of symptoms (ACR/Eular classification criteria, 2010). Early, remission-oriented and adapted treatment with DMARDs ("treating to target") leads to several years of normal bodily function without disability in 40% to 60% of patients. Treatment by an interdisciplinary team promotes the achievement of this goal. The risks associated with this form of treatment are low, with a dropout rate of less than 1 per 100 patient-years. Life-threatening complications are rare. Early diagnosis, intervention with DMARDs in the first three months of disease, and the achievement of a remission minimize the adverse sequelae of RA. The sequential introduction of DMARDs, including biological agents in non-responders, as part of a treat-to-target concept optimizes the long-term outcome, as has been demonstrated in clinical trials for periods of up to eight years.

SAT0044 Five-Year Favourable Outcome of Patients with Early Rheumatoid Arthritis in the 2000S: Data from the Espoir Cohort

ObjectivesTo report the 5-year outcome of a large prospective cohort of patients with very early rheumatoid arthritis (RA), and to identify predictive factors of outcome.MethodsPatients were recruited if they had...

AB0262 PTPN22 1858C>T polymorphism is a negative biomarker of (eular good) response to methotrexate in a cohort of early rheumatoid arthritis

BackgroundA tight control strategy is necessary for an optimal management of early rheumatoid arthritis (ERA). However, it is not sufficient because there is a huge need of biomarkers in order...

OP0237-HPR Upper Limb Exercise, Education and Self Management in Early Rheumatoid Arthritis (The Extra Programme)- Results from a Randomised Controlled Trial

BackgroundUpper limb dysfunction occurs early in people with rheumatoid arthritis (RA) and deteriorates as disease progresses, impacting on independence. Exercise is a key component in the management of upper limb...

SAT0060 Tight Control Schedules Could be a Burden to Patients with Early RA, but they do not Negatively Impact the Improved Quality of Life Via Decreased Disease Activity - Results from the Camera Trials

BackgroundTight control with treat-to-target as treatment strategy is widely used to prevent a severe outcome of rheumatoid arthritis (RA). Our CAMERA (Computer Assisted Management of Early Rheumatoid Arthritis)1 study demonstrated...