Search

IntroductionThe new American College for Rheumatology (ACR)/European League Against Rheumatism (EULAR) remission criteria are based on the assessment of 28 joints. A study was undertaken to study the consequences of remission misclassification due to residual disease activity in the feet on physical function and joint damage in the subsequent year in an observational early disease cohort.MethodsAll patients with rheumatoid arthritis at inclusion or at 1-year follow-up in the early arthritis cohort of the Jan van Breemen Institute, The Netherlands were included. ACR/EULAR remission definitions for trials and clinical practice were calculated twice, once using a 28-joint count and once using a 38-joint count that included the 10 metatarsophalangeal joints. Disease stability was defined as stable x-ray scores over 1 year (change ≤0 in Sharp/van der Heijde scores) and stable and low scores on the Health Assessment Questionnaire (HAQ change ≤0 and HAQ score consistently ≤0.5), all during the second year after inclusion. Analyses comprised residual disease activity (swollen or tender joints >0) in the feet of patients who fulfilled the candidate remission criteria using a 28-joint count and likelihood ratios of remission definitions to predict disease stability.ResultsOf 421 patients, 9–15% reached remission at 1 year using a 28-joint count. Of these, 26–40% showed activity in the feet. Misclassification due to reduced joint counts was observed in 2–3%. A state of remission increased the likelihood of stability of both x-ray and HAQ, with similar likelihood ratios for definitions using 38-joint counts and those using 28-joint counts.ConclusionThe ability of remission definitions with 28-joint counts versus 38-joint counts to predict long-term good radiological and functional outcome is similar. This confirms that inclusion of ankles and forefeet in the assessment of remission is not required, although inclusion of these joints in the examination is recommended.

Objective. To compare the efficacy of MTX and MTXþTNF inhibitors (TNFis) in elderly patients with RA with that in patients of younger age. Methods. Data from two large, randomized, controlled, double-blind trials in patients with early RA using adalimumab or infliximabþMTX or MTX alone were obtained and pooled. Composite disease activity indices were calculated at baseline and 1 year of treatment, and compared in groups of patients classified by quartiles of age with the highest age group comprising 61-82 years using analysis of variance or Kruskal- Wallis test. Results. Across all age quartiles, improvement on MTX was similar with respect to changes of composite disease activity indices, assess- ment of physical function and X-ray progression. Likewise, TNFiþMTX had similar effects across all age groups, but the effects of the combination were more profound than those of MTX monotherapy. Also in 10% of the patients with the highest age, primarily septuagenarians, improvement was seen to a similar degree as in the younger ones. Conclusions. Responsiveness of elderly patients with RA to MTX or TNFiþMTX is similar to that observed in patients of younger age. RA is the most common chronic inflammatory joint disease in adults, affecting 0.5-1% of the population. The incidence of RA increases with age, peaking between the fourth and sixth decade (1). Secular trends in time suggest that the mean age at diagnosis increases, as observed in a Finnish cohort, where the age of onset changed from a mean of 50 to almost 60 years during just one decade and the incidence rates declined in the younger age groups (2). These observations, in line with the increasing life expectancy in the industrialized world, suggest that the number of elderly patients requiring DMARD therapy will increase. The most important long-term consequence of RA is physical disability, which, however, is difficult to interpret. Disability has a component related to disease activity, which is reversible, and a component related to joint damage, which is irreversible (3). In elderly RA patients, the reasons of physical disability are even more complex, since the decline of physical function related to ageing must be considered (4). It has been suggested that RA in the elderly is a phenotypic variant and has an intrinsically different course compared with RA in younger individuals (5). This concept is further supported by reports on differences in the genetics of RA in the elderly (6). In light of these findings, it is of particular importance to under- stand the efficacy of DMARDs in elderly patients with established RA, since only DMARD therapy can effectively interfere with active disease, joint damage, and is able to prevent disability. The effect of DMARDs in elderly patients with RA has not been a main research focus over the past years, although two recent reports have found good clinical effects of disease modification, including the use of TNF inhibitors (TNFis), in elderly individuals (7, 8). However, the vast majority of these patients had longstand- ing disease; and in one of the studies, physical function in elderly RA patients did not improve. In contrast to studies of NSAIDs (9- 11), no major clinical trials have been designed addressing this particular population. Moreover, a recent review concluded that 'data are insufficient to provide much confidence in the potential beneficial effects of DMARDs in the elderly' (11). Therefore, older patients with RA are still less likely to receive DMARD treatment than their younger counterparts, and increas- ing age has been found to be an important determinant of less intensive RA care (12-14). As a consequence of applying less effective therapies, functional impairment might progress more rapidly in the elderly compared with younger patients with RA, especially since physical function is already naturally reduced in the elderly (4). The rapid decline in function could be further aggravated by a higher disease activity at onset. Together with an ineffective DMARD therapy, this may result in more radio- graphic damage as it has been observed in elderly when compared with younger patients with early RA (15). Based on these data, RA in the elderly could be viewed as not only being more severe, but also being less responsive to DMARD therapy. In the present study, we focused on patients with early RA to obviate potential effects of long disease duration on outcomes. We performed a subanalysis of pooled clinical trial data, and assessed the effect of age on the responsiveness of disease activity, physical function and joint damage in patients with early RA treated with MTX, or a combination of MTX with TNFi therapy.

Objective To compare the value of reporting treatment effects in rheumatoid arthritis (RA) as relative change from baseline (e.g., American College of Rheumatology [ACR] responder status) with the value of evaluating absolute disease activity states (e.g., remission). Methods We pooled data from several recent RA clinical trials and evaluated patients who had completed a 1-year treatment period (n = 629). We compared levels of functional impairment and radiographic progression among patients meeting the ACR 50% or 70% improvement criteria (ACR50 and ACR70 responders, respectively) who attained remission of disease, low disease activity, or moderate disease activity after 1 year, as assessed by the Simplified Disease Activity Index and the Disease Activity Score in 28 joints. Results Within the ACR50 and ACR70 responder groups, functional disability and radiographic progression were lowest in patients who had attained disease remission at 1 year, compared with those who had attained low or moderate disease activity. When patients attained the same disease activity category, physical function and radiographic progression did not differ significantly with different response states. Conclusion Functional and radiographic outcomes are different in patients depending on the disease activity category they attain, even if the same level of response (change from baseline) is achieved. Among patients who attain the same disease activity category, the degree of response they experience does not seem to matter. Assessing actual disease activity as well as disease activity states should constitute an integral part of clinical trial data reporting.

ObjectiveRemission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used definition of remission that is stringent but achievable and could be applied uniformly as an outcome measure in clinical trials. This work was undertaken to develop such a definition.MethodsA committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism, and the Outcome Measures in Rheumatology Initiative met to guide the process and review prespecified analyses from RA clinical trials. The committee requested a stringent definition (little, if any, active disease) and decided to use core set measures including, as a minimum, joint counts and levels of an acute-phase reactant to define remission. Members were surveyed to select the level of each core set measure that would be consistent with remission. Candidate definitions of remission were tested, including those that constituted a number of individual measures of remission (Boolean approach) as well as definitions using disease activity indexes. To select a definition of remission, trial data were analysed to examine the added contribution of patient-reported outcomes and the ability of candidate measures to predict later good radiographic and functional outcomes.ResultsSurvey results for the definition of remission suggested indexes at published thresholds and a count of core set measures, with each measure scored as 1 or less (eg, tender and swollen joint counts, C reactive protein (CRP) level, and global assessments on a 0–10 scale). Analyses suggested the need to include a patient-reported measure. Examination of 2-year follow-up data suggested that many candidate definitions performed comparably in terms of predicting later good radiographic and functional outcomes, although 28-joint Disease Activity Score–based measures of remission did not predict good radiographic outcomes as well as the other candidate definitions did. Given these and other considerations, we propose that a patient's RA can be defined as being in remission based on one of two definitions: (1) when scores on the tender joint count, swollen joint count, CRP (in mg/dl), and patient global assessment (0–10 scale) are all ≤1, or (2) when the score on the Simplified Disease Activity Index is ≤3.3.ConclusionWe propose two new definitions of remission, both of which can be uniformly applied and widely used in RA clinical trials. The authors recommend that one of these be selected as an outcome measure in each trial and that the results on both be reported for each trial.

OBJECTIVE: /st> To apply a data-driven approach to investigate, in patients newly presenting with undifferentiated inflammatory synovitis, key variables that discriminate the subset of patients at sufficiently high risk of persistent or erosive disease for the purpose of developing new criteria for rheumatoid arthritis (RA). METHODS: /st> In this first phase of the collaborative effort of the American College of Rheumatology and European League Against Rheumatism to develop new criteria for RA, a pooled analysis of early arthritis cohorts made available by the respective investigators is presented. All the variables associated with the gold standard of treatment with methotrexate during the first year after enrolment were first identified. Principal component analysis was then used to identify among the significant variables those sets that represent similar domains. In a final step, from each domain one representative variable was extracted, all of which were then tested for their independent effects in a multivariate regression model. From the OR in that final model, the relative weight of each variable was estimated. RESULTS: /st> The final domains and variables identified by this process (and their relative weights) were: swelling of a metacarpophalangeal joint (MCP; 1.5), swelling of a proximal interphalangeal joint (PIP; 1.5), swelling of the wrist (1.5), tenderness of the hand (ie, MCP, PIP or wrist (2)), acute phase reaction (ie, C reactive protein or erythrocyte sedimentation rate and weights for moderate or high elevations of either one (1 for moderate, 2 for high elevation)) and serological abnormalities (ie, rheumatoid factors or anti-citrullinated protein antibodies, again with separate weights for moderate or high elevations (2 and 4, respectively)). CONCLUSION: /st> The results of this first phase were subsequently used in the second phase of the project, which is reported in a separate methodological paper, and for derivation of the final set of criteria

Background and objectives Instruments for measuring disease activity in psoriatic arthritis (PsA) are not yet firmly established, and most of the currently employed ones have been derived for rheumatoid arthritis. Some of these instruments are based on 28 joint counts, which do not capture joints frequently affected in PsA. Therefore, the reliability and validity of DAREA (for ‘Disease Activity index for REactive Arthritis’), which was originally developed for reactive arthritis and employs a 66/68 joint count, was tested in patients with PsA. Methods Trial data from the Infliximab Multinational Psoriatic Arthritis Controlled Trial were analysed. Results were then independently validated using an observational data set. DAREA was compared to other composite indices regarding correlations with core set variables, sensitivity to change and criterion validity. Results Good correlation of the DAREA with single items of disease activity, other composite scores (r=0.6−0.9) and physical function (Health Assessment Questionnaire; r=0.5) was found. Likewise, DAREA was at least as sensitive to change as the other indices and more so in patients with distal interphalangeal joint involvement. Additionally, DAREA correlated well with radiographic changes. Conclusion The analyses of this study provide evidence of the utility and validity of the DAREA for PsA disease activity assessment. A second name should therefore be assigned to this score: DAPSA (for ‘Disease Activity index for PSoriatic Arthritis’).

Objective Joint damage is related to disease activity in rheumatoid arthritis (RA), but the degree of its progression and the temporal associations between disease activity and joint damage are unclear. The aim of this study was to evaluate whether there is a latency in the effect of disease activity on radiographic progression in patients with RA. Methods Data were obtained from the PREMIER trial, a 2-year randomized, controlled clinical trial of adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in early RA. Radiographic progression of joint damage was calculated using the modified total Sharp score in a subset of patients whose disease was in remission (Simplified Disease Activity Index ≤3.3) in the second year of the trial. The progression of damage in the second year was compared between groups of patients whose disease was already in remission for an additional period of 3, 6, or 9 months during the first year. Analysis of variance was used to test for a linear trend. Results Among 794 patients with early RA, 119 (15%) achieved sustained remission during the second year, with no difference in radiographic progression across the 3 treatment groups. Radiographic progression in the second year was significantly different between patients with 3, 6, or 9 additional months of remission during year 1 (mean change in the modified Sharp score 1.19 in those with 3 additional months of remission versus 0.20 in those with 6 additional months of remission and −0.32 in those with 9 additional months of remission; P < 0.05). The results were supported by similar findings in a series of sensitivity analyses. Conclusion These data indicate that the level of disease activity as well as the duration of remission affect subsequent progression of radiographic damage in RA. This latency between disease activity and its effects on radiographic progression should be considered when evaluating radiographic outcomes in trials of RA.

Objective To analyze the minimum clinically important improvement (MCII) of disease activity measures in rheumatoid arthritis (RA) using patient-derived anchors, and to assess whether criteria for improvement differ with baseline disease activity. Methods We used data from a Norwegian observational database comprising 1,050 patients (73% women, 65% rheumatoid factor-positive, mean duration of RA 7.7 years). At 3 months after initiation of therapy, patients indicated whether their condition had improved, had considerably improved, was unchanged, had worsened, or had considerably worsened. We used receiver operating characteristic curve analysis to determine the MCII for the Disease Activity Score based on the assessment of 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI), and analyzed the effects of different levels of baseline disease activity on the MCII. Results On average, patients started with high disease activity and improved significantly during treatment (American College of Rheumatology 20%, 50%, and 70% improvement criteria responses were 37%, 17%, and 5%, respectively). The overall mean (95% confidence interval [95% CI]) thresholds for MCII after 3 months for the DAS28, SDAI, and CDAI were 1.20 (95% CI 1.18–1.22), 10.95 (95% CI 10.69–11.20), and 10.76 (95% CI 10.49–11.04), respectively, and the mean (95% CI) thresholds for major responses were 1.82 (95% CI 1.80–1.83), 15.82 (95% CI 15.65–16.00), and 15.00 (95% CI 14.82–15.18), respectively. With increasing disease activity, much higher changes in disease activity were needed to achieve MCII according to patient judgment. Conclusion The perception of improvement of disease activity of patients with RA is considerably different depending on the disease activity level at which they start.

Joint destruction in rheumatoid arthritis is comprised of cartilage and bone damage, which can be evaluated radiographically separately by the joint space narrowing (JSN) and erosion (ERO) scores. It is currently unclear to which extent these components affect irreversible functional disability. The aim of the present work was to determine these contributions.Data, kindly provided by the sponsors, was evaluated from several randomised controlled clinical trials on adalimumab, etanercept, infliximab and leflunomide. Patients who reached stringent remission according to the Simplified Disease Activity Index (SDAI≤3.3) were extracted to eliminate the activity related (ie, reversible) component of disability. In these patients, residual Health Assessment Questionnaire Disability Index (HAQ-DI) score at the time of remission (to reflect the level of 'irreversible' disability) was determined and related to baseline measures of ERO and JSN scores univariately, by stratification and in adjusted regression models.A total of 748 patients who achieved a state of remission were analysed (16.3% of the total pooled population of 4602 patients). In the univariate analyses, mean residual HAQ-DI values in remission were significantly larger in higher tertiles of JSN and ERO (ERO: 0.21, 0.25, 0.35; JSN: 0.19, 0.24, 0.39; p0.001 for both). In stratified analyses, mean residual HAQ-DI scores were larger in higher tertiles of JSN within the first tertile of ERO (0.18, 0.25, 0.29; p=0.05), as well as the second (0.21, 0.24, 0.29; p=0.19) and the third (0.12, 0.23, 0.42; p0.001). In contrast, there was no such trend across ERO tertiles within the first JSN tertile (0.18, 0.21, 0.12; p=0.99) and the second tertile (0.25, 0.24, 0.23; p=0.77), and only marginally within the third tertile of JSN (0.29, 0.29, 0.42; p=0.07). Adjusted multivariate regression models supported the significant association of JSN on residual disability.Cartilage damage appears to be the more clearly associated with irreversible physical disability than bony damage. These data suggest that particular attention should be given to therapeutic interference with cartilage destruction.