Disease activity level, remission and response in established rheumatoid arthritis: Performance of various criteria sets in an observational cohort, treated with anti-TNF agents

<p>Abstract</p> <p>Background</p> <p>Most composite indices of disease activity and response criteria in RA have been validated and compared in clinical trials rather than routine care. We therefore wanted to compare the performance of the DAS28, SDAI and CDAI activity indices, their activity states, their response criteria, and also compare with the ACR response criteria in an observational clinical setting.</p> <p>Methods</p> <p>Agreement between the criteria sets was investigated using κ statistics in a non-randomized cohort of 1789 RA patients from southern Sweden, starting their first course of anti-TNF-treatment. Mean disease duration was 12 years. Completer analysis was used.</p> <p>Results</p> <p>Agreement between high, moderate and low activity states was moderate or substantial, with κ = 0.5 or better for all criteria. Agreement between SDAI and CDAI disease states was > 90% in these categories with κ > 0.8. DAS28 original and modified cut point remission had good agreement (κ = 0.91). Agreement between responses was substantial at the overall/ACR20 level (about 95%, κ = 0.7 or better) for all criteria. By contrast, agreement was poor between moderate and high level responses.</p> <p>Conclusion</p> <p>Disease activity states according to the various indices perform similarly and show substantial agreement at all levels except remission. Agreement between SDAI and CDAI states is excellent. Response criteria, applied at the individual patient level, are hard to interpret and show poor agreement, except at the lowest level of response. Thus, they should not be applied uncritically in clinical practice.</p

Symptom complexes in patients with seropositive arthralgia and in patients newly diagnosed with rheumatoid arthritis: a qualitative exploration of symptom development

Objective: The aim of this study was to explore symptoms and symptom development during the earliest phases of rheumatoid arthritis (RA) in patients with seropositive arthralgia and patients newly diagnosed with RA

Impact of patient global assessment on achieving remission in patients with rheumatoid arthritis: A multinational study using the METEOR database

OBJECTIVE: There is an ongoing debate about excluding patient's global assessment (PtGA) from composite and Boolean-based definitions of rheumatoid arthritis (RA) remission. This study aimed at determining the influence of PtGA on RA disease states, exploring differences across countries, and understanding the association between PtGA, measures of disease impact (symptoms), and markers of disease activity (inflammation). METHODS: Cross-sectional data from the Measurement of Efficacy of Treatment in the Era of Outcome in Rheumatology international database were used. We calculated the proportion of patients failing American College of Rheumatology/European League Against Rheumatism Boolean-based remission (4-variable remission) solely due to PtGA (PtGA-near-remission) in the overall sample and in the most representative countries (i.e., those with >3,000 patients in the database). Multivariable linear regression models were used to identify the main determinants of PtGA, grouped in predominantly inflammatory impact factors (28 tender joint counts, 28 swollen joint counts, and C-reactive protein level) and disease impact factors (pain and function). RESULTS: This study included 27,768 patients. Excluding PtGA from the Boolean-based definition (3-variable remission) increased the remission rate from 5.8% to 15.8%. The rate of PtGA-near-remission varied considerably between countries, from 1.7% in India to 17.9% in Portugal. One-third of the patients in PtGA-near-remission group scored PtGA >4 of 10. Pain and function were the main correlates of PtGA, with inflammation-related variables contributing less to the model (R2 = 0.57). CONCLUSION: PtGA is moderately related to joint inflammation overall, but only weakly so in low levels of disease activity. A considerable proportion of patients otherwise in biologic remission still perceive high PtGA, putting them at risk of excessive immunosuppressive treatment

Interpretation of DAS28 and its components in the assessment of inflammatory and non-inflammatory aspects of rheumatoid arthritis

Background: DAS28 is interpreted as the inflammatory disease activity of RA. Non-inflammatory pain mechanisms can confound assessment. We aimed to examine the use of DAS28 components or DAS28-derived measures that have been published as indices of non-inflammatory pain mechanisms, to inform interpretation of disease activity. Methods: Data were used from multiple observational epidemiology studies of people with RA. Statistical characteristics of DAS28 components and derived indices were assessed using baseline and follow up data from British Society for Rheumatology Biologics Registry participants [1] commencing anti-TNF therapy (n = 10813), or [2] changing between non-biologic DMARDs (n=2992), [3] Early Rheumatoid Arthritis Network participants (n=813), and [4] participants in a cross-sectional study exploring fibromyalgia and pain thresholds (n=45). Repeatability was tested in 34 patients with active RA. Derived indices were the proportion of DAS28 attributable to patient-reported components (DAS28-P), tender-swollen difference and tender:swollen ratio. Pressure pain detection threshold (PPT) was used as an index of pain sensitisation. Results: DAS28, tender joint count, visual analogue scale, DAS28-P, tender-swollen difference and tender:swollen ratio were more strongly associated with pain, PPT and fibromyalgia status than were swollen joint count or erythrocyte sedimentation rate. DAS28-P, tender-swollen difference and tender:swollen ratio better predicted pain over 1 year than did DAS28 or its individual components. Conclusions: DAS28 is strongly associated both with inflammation and with patient-reported outcomes. DAS28-derived indices such as tender-swollen difference are associated with non-inflammatory pain mechanisms, can predict future pain and should inform how DAS28 is interpreted as an index of inflammatory disease activity in RA

Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate

Contains fulltext : 80996.pdf (publisher's version ) (Closed access)OBJECTIVE: To validate and compare the definition of the Disease Activity Score 28 based on C-reactive protein (DAS28 (CRP)) to the definition based on erythrocyte sedimentation rate (ESR). METHODS: Data were analysed from two randomised, double-blind, placebo-controlled trials of abatacept of 6-month and 12-month duration in patients with rheumatoid arthritis. European League Against Rheumatism (EULAR) response criteria and the proportion of patients in remission (DAS28 <2.6) based on the two DAS28 definitions were examined. Trends in radiographic progression (erosion score, joint space narrowing score and total score) and physical function (Health Assessment Questionnaire Disability Index (HAQ-DI)) across the EULAR responder states (none, moderate and good) were analysed. RESULTS: There was general agreement in determining the EULAR responder state using both DAS28 definitions (kappa = 0.80, 95% CI 0.76 to 0.83). Overall, there was 82.4% agreement on the EULAR response criteria; when disagreements occurred, the DAS28 (CRP) yielded a better EULAR response more often then DAS28 (ESR) (12.6% vs 4.9%, respectively). There was also agreement in determining remission: kappa = 0.69 (95% CI 0.60 to 0.78). Radiographic progression decreased in patients treated with abatacept across EULAR states (from none to moderate to good) based on both definitions. For patients treated with placebo, the trend was not as pronounced, with radiographic scores higher for moderate vs non-responders. For physical function, similar trends were observed across the EULAR states for both DAS28 definitions. CONCLUSIONS: The DAS28 (CRP) has been validated against radiographic progression and physical function. While the DAS28 (CRP) yielded a better EULAR response more often than the DAS28 (ESR), the validation profile was similar to the DAS28 (ESR), indicating that both measures are useful for assessing disease activity in patients with rheumatoid arthritis

HDL cholesterol efflux capacity in rheumatoid arthritis patients: contributing factors and relationship with subclinical atherosclerosis

Background: Lipid profiles appear to be altered in rheumatoid arthritis (RA) patients because of disease activity and inflammation. Cholesterol efflux capacity (CEC), which is the ability of high-density lipoprotein cholesterol to accept cholesterol from macrophages, has been linked not only to cardiovascular events in the general population but also to being impaired in patients with RA. The aim of this study was to establish whether CEC is related to subclinical carotid atherosclerosis in patients with RA. Methods: We conducted a cross-sectional study that encompassed 401 individuals, including 178 patients with RA and 223 sex-matched control subjects. CEC, using an in vitro assay, lipoprotein serum concentrations, and standard lipid profile, was assessed in patients and control subjects. Carotid intima-media thickness (CIMT) and carotid plaques were assessed in patients with RA. A multivariable analysis was performed to evaluate the relationship of CEC with RA-related data, lipid profile, and subclinical carotid atherosclerosis. Results: Mean (SD) CEC was not significantly different between patients with RA (18.9 ± 9.0%) and control subjects (16.9 ± 10.4%) (p = 0.11). Patients with RA with low (? coefficient ?5.2 [?10.0 to 0.3]%, p = 0.039) and moderate disease activity (? coefficient ?4.6 [?8.5 to 0.7]%, p = 0.020) were associated with lower levels of CEC than patients in remission. Although no association with CIMT was found, higher CEC was independently associated with a lower risk for the presence of carotid plaque in patients with RA (odds ratio 0.94 [95% CI 0.89?0.98], p = 0.015). Conclusions: CEC is independently associated with carotid plaque in patients with RA

A core set of risk factors in individuals at risk of rheumatoid arthritis: a systematic literature review informing the EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis

Background There is significant interest in determining risk factors in individuals at risk of rheumatoid arthritis (RA). A core set of risk factors for clinical arthritis development has not been defined. Methods A literature search and systematic literature review (SLR) was conducted to identify risk factors in individuals at risk of RA using Medline, Embase, PubMed and Central databases. Results 3854 articles were identified by the literature search. After screening of titles, 138 abstracts were reviewed and 96 articles finally included. Fifty-three articles included data on risk factors including autoantibodies, subclinical inflammation on imaging, clinical features, serum and cellular biomarkers and genetic markers. Risk factors were dependent on the at-risk population. There was good evidence for serum anticitrullinated protein antibodies (ACPA) levels, as risk factors for arthritis in all at-risk populations (n=13 articles). Subclinical inflammation on ultrasound (n=12) and MRI (n=6) was reported as a risk factor in multiple studies in at-risk individuals with musculoskeletal (MSK) symptoms and undifferentiated arthritis (UA). Clinical features were reported as a risk factor in at-risk individuals with MSK symptoms and UA (n=13). Other risk factors, including serum and cellular markers were less frequently reported. Conclusions Risk factors for arthritis development in RA are specific to the at-risk population. Serum ACPA confers risk in all populations; subclinical inflammation on imaging and clinical features confer risk in at-risk individuals with MSK symptoms. This SLR informed the EULAR taskforce for points to consider on conducting clinical trials and studies in individuals at risk of RA

Characteristics of difficult-to-treat rheumatoid arthritis: results of an international survey

Objectives: Patients with difficult-to-treat rheumatoid arthritis (RA) remain symptomatic despite treatment according to current European League Against Rheumatism (EULAR) management recommendations. These focus on early phases of the disease and pharmacological management. We aimed to identify characteristics of difficult-to-treat RA and issues to be addressed in its workup and management that are not covered by current management recommendations. Methods: An international survey was conducted among rheumatologists with multiple-choice questions on disease characteristics of difficult-to-treat RA. Using open questions, additional items to be addressed and items missing in current management recommendations were identified. Results: 410 respondents completed the survey: 50% selected disease activity score assessing 28 joints &gt;3.2 OR presence of signs suggestive of active disease as characteristics of difficult-to-treat RA; 42% selected fatigue; 48% selected failure to ≥2 conventional synthetic disease-modifying antirheumatic drugs (DMARDs) AND ≥2 biological/targeted synthetic DMARDs; 89% selected inability to taper glucocorticoids below 5 mg or 10 mg prednisone equivalent daily. Interfering comorbidities, extra-articular manifestations and polypharmacy were identified as important issues missing in current management recommendations. Conclusions: There is wide variation in concepts of difficult-to-treat RA. Several important issues regarding these patients are not addressed by current EULAR recommendations