Patient perspective on remission in rheumatoid arthritis: Validation of patient reported outcome instruments to measure absence of disease activity.

OBJECTIVE: Patients have identified pain, fatigue and independence as the most important domains that need to be improved to define remission in rheumatoid arthritis (RA). This study identified and validated instruments for these domains and evaluated their added value to the ACR/EULAR Boolean remission definition. METHODS: Patients with a 28-joint Disease Activity Score (DAS28) ≤3.2 or in self-perceived remission (declaring their disease activity 'as good as gone') from the Netherlands, Portugal, Australia, and Canada, were assessed at 0, 3 and 6 months for patient-reported outcomes and the WHO-ILAR RA core set. Instrument validity was evaluated cross-sectionally, longitudinally and for the ability to predict future good outcome in terms of physical functioning. Logistic regression quantified the added value to Boolean remission. RESULTS: Of 246 patients, 152 were also assessed at 3, and 142 at 6 months. Most instruments demonstrated construct validity and discriminative capacity. Pain and fatigue were best captured by a simple numerical rating scale (NRS). Measurement of independence proved more complex, but a newly developed independence NRS was preferred. NRS for pain, fatigue and independence, in addition to or instead of patient global assessment did not add enough information to justify modification of the current Boolean definition of remission in RA. CONCLUSION: Key elements of the patient perspective on remission in RA can be captured by NRS pain, fatigue, and independence. Although this study did not find conclusive evidence to improve the current definition of remission in RA, the information from these instruments adds value to the physician's assessment of remission and further bridges the gap between physician and patient.

Prevalence and Characteristics of Metabolic Syndrome Differ in Men and Women with Early Rheumatoid Arthritis.

Objective: Metabolic syndrome (MetS) prevalence in early rheumatoid arthritis (ERA) is conflicting. The impact of sex, including menopause, has not been described. We estimated the prevalence and factors associated with MetS in men and women with ERA. Methods: A cross-sectional study of the Canadian Early Arthritis Cohort (CATCH) was performed. Participants with baseline data to estimate key MetS components were included. Sex-stratified logistic regression identified baseline variables associated with MetS. Results: The sample included 1543 participants; 71% were female and the mean age was 54 (SD 15) years. MetS prevalence was higher in men 188 (42%) than women 288 (26%, P < 0.0001) and increased with age. Frequent MetS components in men were hypertension (62%), impaired glucose tolerance (IGT, 40%), obesity (36%), and low high-density lipoprotein cholesterol (36%). Postmenopausal women had greater frequency of hypertension (65%), IGT (32%), and high triglycerides (21%) compared with premenopausal women (P < 0.001). In multivariate analysis, MetS was negatively associated with seropositivity and pulmonary disease in men. Increasing age was associated with MetS in women. In postmenopausal women, corticosteroid use was associated with MetS. Psychiatric comorbidity was associated with MetS in premenopausal women. MetS status was not explained by disease activity or core RA measures. Conclusion: The characteristics and associations of MetS differed in men and women with ERA. Sex differences, including postmenopausal status, should be considered in comorbidity screening. With this knowledge, the interplay of MetS, sex, and RA therapeutic response on cardiovascular outcomes should be investigated.

The influence of age at disease onset on disease activity and disability: results from the Ontario Best Practices Research Initiative.

This study aims to compare characteristics between late-onset rheumatoid arthritis (RA) and young-onset RA and determine the association between age at disease onset and disease severity. We cross-sectionally studied 971 patients at the time of entry into the Ontario Best Practices Research Initiative, a registry of RA patients followed up in routine care. We restricted patients to ≤5 years of disease duration. Late-onset RA was defined as an onset ≥60 years of age and young-onset RA <60 years. Group differences were compared, and multivariate linear regression models were used to test the influence of age at onset on Disease Activity Score in 28 Joints with erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), and Health Assessment Questionnaire (HAQ) scores. The swollen joint count (6.2 vs. 5.3), acute phase reactants (C-reactive protein (CRP) 17.4 vs. 11.8 mg/L, ESR 30.6 vs. 21.5 mm/h), and comorbidity burden were higher in late-onset RA compared to young-onset RA (p < 0.01). Mean DAS28-ESR (4.6 vs. 4.3) and HAQ (1.2 vs. 1.1) scores were higher in late-onset RA patients (p < 0.05). Late-onset RA patients received more initial disease-modifying antirheumatic drug (DMARD) monotherapy and corticosteroids in comparison to greater DMARD/biologic combination therapy in young-onset RA patients (p < 0.05). Adjusted multivariate analyses showed that late-onset RA was independently associated with higher mean DAS28-ESR and HAQ scores, but not CDAI. Late-onset RA patients have greater disease activity that may contribute to disability early in the disease course. Despite this, initial treatment consists of less combination DMARD and biologic use in late-onset RA patients. This may have implications for future response to therapy and development of joint damage, disability, and comorbidities in this group.

Multinational evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative.

OBJECTIVE: To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA). METHODS: 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008-9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007-2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 39,756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA. CONCLUSIONS: Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use.

Efficacy of initial methotrexate monotherapy versus combination therapy with a biological agent in early rheumatoid arthritis: a meta-analysis of clinical and radiographic remission.

OBJECTIVE: The target outcome in early rheumatoid arthritis (ERA) is now remission. This meta-analysis compared the efficacy of initial methotrexate monotherapy versus combination therapy (methotrexate plus biological agent) for clinical remission and radiographic non-progression among ERA patients with minimal or no previous methotrexate exposure. METHODS: A systematic search was performed for randomised controlled trials of ERA using predefined criteria. A random effects model was used to pool the risk ratio (RR) for clinical and radiographic remission at 52-56 weeks of follow-up. RESULTS: Seven trials of combination therapy with infliximab, adalimumab, etanercept or abatacept were included. The majority of studies defined clinical remission as a 28-joint disease activity score (DAS28) of 2.6 or less. Radiographic non-progression was primarily defined as a modified total Sharp score change of less than 0.5 units. All trials demonstrated risk estimates in favour of combination therapy: the pooled RR for achieving clinical remission was 1.74 (95% CI 1.54 to 1.98) and for radiographic non-progression was 1.30 (95% CI 1.01 to 1.68). Significant heterogeneity among studies for the latter outcome was detected (p<0.001). CONCLUSIONS: The efficacy of combination therapy with a biological agent is superior to methotrexate monotherapy for remission. Combination therapy has a greater initial effect on clinical remission than radiographic non-progression. Uniform definitions of remission are needed and the proportion of subjects who achieve the combined endpoint of clinical and radiographic remission should be considered as a meaningful outcome in future studies of ERA.

Validation of a prediction rule for development of rheumatoid arthritis in patients with early undifferentiated arthritis.

OBJECTIVE: To validate a model which predicts progression from undifferentiated arthritis (UA) to RA, in a Canadian UA cohort. METHODS: The prediction rule, comprising variables which are scored from 0 to 13, with higher scores reflecting an increased risk of RA, was applied to baseline characteristics of all patients with UA. Progression to RA was determined at 6 months. RESULTS: 105 patients were identified. By 6 months, 80 (76%) had developed RA while 25 (24%) had developed another diagnosis. Number of tender and swollen joints, rheumatoid factor positivity, anti-cyclic citrullinated peptide positivity, poor functional status and high disease activity were associated with development of RA (p<0.01). Median prediction score was 8.0 for progressors, 5.0 for non-progressors. With these cut-off points, 18 (72%) patients with scores < or =5 did not develop RA, while 35 (97%) with scores > or =8 did develop RA. CONCLUSIONS: High scores in our cohort predicted those who progressed to RA by 6 months. Baseline scores > or =8 corresponded with higher rates of progression.