Rheumatoid Arthritis: Aletaha D

Aletaha D, Smolen JS. · Division of Rheumatology, Department of Internal Medicine III, University of Vienna, Vienna General Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria. · Clin Exp Rheumatol. · Pubmed #14969071 No free full text.

Abstract: The concept of early and aggressive therapy of rheumatoid arthritis (RA) has been well documented in the past years. It includes immediate DMARD institution after diagnosis, the use of the most effective DMARDs, and rapid switching of regimens if a level of disease activity close to remission is not achieved. In this review we briefly explore to what degree this new concept has been implemented in routine clinical care. Based on an observational dataset comprising 3342 DMARD courses, we present evidence of a change in DMARD patterns in newly diagnosed RA patients towards a higher prescription rate of more aggressive drugs like methotrexate (MTX), as well as a decreasing lag time until MTX was instituted in RA patients over the years. One consequence of recent changes in therapeutic strategies is that comparative analyses of formerly versus recently employed DMARDs will be considerably biased in observational studies. By contrast to changes in DMARD usage, survey data show neither a shortening of referral time nor a change in the approach to diagnose early RA. These data indicate a need for more dissemination of the early arthritis concept.

Aletaha D, Smolen JS. · Division of Rheumatology, Department of Internal Medicine III, University of Vienna, Vienna General Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria. · Curr Rheumatol Rep. · Pubmed #14609484 No free full text.

This publication has no abstract.

Aletaha D, Smolen JS. · Division of Rheumatology, Department of Internal Medicine III, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna. · Acta Med Austriaca. · Pubmed #11899747 No free full text.

Abstract: Our goal was to evaluate the state of nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis (RA), before the introduction of the coxibs. The prerequisite for inclusion was the presence of RA (ACR criteria) plus therapy with an NSAID with or without a disease modifying antirheumatic drug (DMARD). A total of 368 consecutive RA patients (81% women) from the outpatient clinic at the Vienna General Hospital were included. Rheumatoid factor was positive in 62%, the patients' mean age was 60 +/- 14 years. The period of observation was 1972-1998. Seventy-seven per cent of the patients had DMARD and NSAID therapy. NSAID therapy was dominated by diclofenac, accounting for 60% of all therapies. Eighteen other substances were applied more rarely. All NSAIDs together were given for 768 patient years (with a mean duration of therapy of 17 years +/- 21 months). Seventy-two per cent of the patients received GI-protective therapy mainly with histamine antagonists and sucralfate while on nonsteroidal therapy. NSAID toxicity mostly affected the GI tract. There was a similar incidence of GI-related adverse events between patients with and patients without GI protection, mainly dyspepsia and nausea. NSAIDs have the potential to cause adverse events in the GI tract. Therapy with histamine antagonists or sucralfate did not reduce the patients' rate of gastrointestinal adverse events.

Aletaha D, Funovits J, Breedveld FC, Sharp J, Segurado O, Smolen JS. · Division of Rheumatology, Medical University of Vienna, Vienna, Austria. · Arthritis Rheum. · Pubmed #19404938 No free full text.

Abstract: 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<or=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.

Dougados M, Schmidely N, Le Bars M, Lafosse C, Schiff M, Smolen JS, Aletaha D, van Riel P, Wells G. · Rene Descartes University, Medicine Faculty, UPRES-EA 4058, APHP, Cochin Hospital, Rheumatology B Department, Paris, France. · Ann Rheum Dis. · Pubmed #19074177 links to  free full text

Abstract: OBJECTIVES: To evaluate different methods of reporting response to treatment or disease status for their ability to discriminate between active therapy and placebo, or to reflect structural progression or patient satisfaction with treatment using an exploratory analysis of the Abatacept in Inadequate Responders to Methotrexate (AIM) trial. METHODS: 424 active (abatacept approximately 10 mg/kg) and 214 placebo-treated patients with rheumatoid arthritis (RA) were evaluated. METHOD: of reporting included: (1) response (American College of Rheumatology (ACR) criteria) versus state (disease activity score in 28 joints (DAS28) criteria); (2) stringency (ACR20 vs 50 vs 70; moderate disease activity state (MDAS; DAS28 <5.1) vs low disease activity state (LDAS; DAS28 <or=3.2) vs DAS28-defined remission (DAS28 <2.6)); (3) time to onset (time to first ACR50/LDAS) and (4) sustainability of ACR50/LDAS for consecutive visits. Methods were assessed according to: (1) discriminatory capacity (number of patients needed to study (NNS)); (2) structural progression (Genant-modified Sharp score) and (3) patient satisfaction with treatment. Positive likelihood ratios (LR) evaluated the ability of the above methods to reflect structural damage and patient satisfaction. RESULTS: MDAS and ACR20 had the highest discriminatory capacity (NNS 49 and 69). Sustained LDAS best reflected no radiographic progression (positive LR >or=2). More stringent criteria (at least ACR50/LDAS), faster onset (<or=3 months) and sustainability (>3 visits) of ACR50/LDAS best reflected patient satisfaction (positive LR >10). CONCLUSIONS: The optimal method for reporting a measure of disease activity may differ depending on the outcome of interest. Time to onset and sustainability can be important factors when evaluating treatment response and disease status in patients with RA.

Schueller-Weidekamm C, Krestan C, Schueller G, Kapral T, Aletaha D, Kainberger F. · Department of Diagnostic Radiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. · AJR Am J Roentgenol. · Pubmed #17242261 links to  free full text

Abstract: OBJECTIVE: This study evaluates the value of contrast-enhanced pulse-inversion harmonic imaging (PIHI) to detect synovial vascularization and thus the therapeutic effects of prednisolone treatment on the inflammation in finger joints in rheumatoid arthritis (RA). MATERIALS AND METHODS: Before and after 7 days of mid- to high-dose steroid therapy, blood tests and clinical and sonographic examinations were assessed in 14 patients. Two hundred eighty finger joints (metacarpophalangeal [MCP] I-V, interphalangeal [IP], and proximal interphalangeal [PIP] II-V) were investigated on power Doppler sonography to determine, in each patient, the finger joint with the strongest hypervascularization and to score the synovial vascularization. Further dynamic examination of the selected joint was performed on PIHI after i.v. administration of a second-generation sonographic contrast medium. Vascularization was quantified by calculating the area under the time-intensity curves. The changes in signal intensities before and after therapy were correlated with clinical examinations (disease activity score [DAS]). RESULTS: The score of the joint with the strongest hypervascularization assessed by power Doppler sonography decreased significantly from 1.7 to 1.3 (p < 0.01); however, in six patients, no change was assessed after steroid therapy. In all patients, a significant reduction in PIHI signals was observed after therapy (p < 0.05). The baseline and follow-up median values of the area under the time-intensity curves were 8.56 +/- 1.28 and 7.65 +/- 0.66, respectively. The median values of the DAS decreased significantly from 4.90 +/- 0.86 to 3.6 +/- 1.0 (p < 0.01) 7 days after the steroid therapy. CONCLUSION: PIHI and power Doppler sonography enable the detection of synovial perfusion alterations after steroid therapy and, therefore, may be useful tools for the evaluation of active inflammation in RA and for the assessment of therapeutic response. However, minor changes of synovial vascularization can be better detected on PIHI than on power Doppler sonography.

Kapral T, Stamm T, Machold KP, Montag K, Smolen JS, Aletaha D. · Department of Rheumatology, Internal Medicine III, Medical University of Vienna, Vienna, Austria. · Arthritis Res Ther. · Pubmed #16507172 links to  free full text

Abstract: Effectiveness of therapy with individual disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is limited, and the number of available DMARDs is finite. Therefore, at some stage during the lengthy course of RA, institution of traditional DMARDs that have previously been applied may have to be reconsidered. In the present study we investigated the effectiveness of re-employed methotrexate in patients with a history of previous methotrexate failure (original course). A total of 1,490 RA patients (80% female, 59% rheumatoid factor positive) were followed from their first presentation, yielding a total of 6,470 patient-years of observation. We identified patients in whom methotrexate was re-employed after at least one intermittent course of a different DMARD. We compared reasons for discontinuation, improvement in acute phase reactants, and cumulative retention rates of methotrexate therapy between the original course of methotrexate and its re-employment. Similar analyses were peformed for other DMARDs. Methotrexate was re-employed in 86 patients. Compared with the original courses, re-employment was associated with a reduced risk for treatment termination because of ineffectiveness (P = 0.02, by McNemar test), especially if the maximum methotrexate dose of the original course had been low (<12.5 mg/week; P = 0.02, by logistic regression). In a Cox regression model, re-employed MTX was associated with a significantly reduced hazard of treatment termination compared with the original course of methotrexate, adjusting for dose and year of employment (hazard ratio 0.64, 95% confidence interval 0.42-0.97; P = 0.04). These findings were not recapitulated in analyses of re-employment of other DMARDs. Re-employment of MTX despite prior inefficacy, but not re-employment of other DMARDs, is an effective therapeutic option, especially in those patients in whom the methotrexate dose of the original course was low.

Gülfe A, Aletaha D, Saxne T, Geborek P. · Dept of Rheumatology, Lund University Hospital, Lund, Sweden. · BMC Musculoskelet Disord. · Pubmed #19389230 links to  free full text

Abstract: BACKGROUND: 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. METHODS: Agreement between the criteria sets was investigated using kappa 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. RESULTS: Agreement between high, moderate and low activity states was moderate or substantial, with kappa = 0.5 or better for all criteria. Agreement between SDAI and CDAI disease states was > 90% in these categories with kappa > 0.8. DAS28 original and modified cut point remission had good agreement (kappa = 0.91). Agreement between responses was substantial at the overall/ACR20 level (about 95%, kappa = 0.7 or better) for all criteria. By contrast, agreement was poor between moderate and high level responses. CONCLUSION: 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.

Aletaha D, Funovits J, Ward MM, Smolen JS, Kvien TK. · Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria. · Arthritis Rheum. · Pubmed #19248136 No free full text.

Abstract: 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.

Smolen JS, Aletaha D. · Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, and 2nd Department of Medicine, Hietzing Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria. · Arthritis Res Ther. · Pubmed #19232060 links to  free full text

Abstract: The changes occurring in the field of rheumatoid arthritis (RA) over the past decade or two have encompassed new therapies and, in particular, a new look at the clinical characteristics of the disease in the context of therapeutic improvements. It has been shown that composite disease activity indices have special merits in following patients, that disease activity governs the evolution of joint damage, and that disability can be dissected into several components--among them disease activity and joint damage. It has also been revealed that aiming at any disease activity state other than remission (or, at worst, low disease activity) is associated with significant progression of joint destruction, that early recognition and appropriate therapy of RA are important facets of the overall strategy of optimal clinical control of the disease, and that tight control employing composite scores supports the optimization of the therapeutic approaches. Finally, with the advent of novel therapies, remission has become a reality and the treatment algorithms encompassing all of the above-mentioned aspects will allow us to achieve the rigorous aspirations of today and tomorrow.

Aletaha D, Smolen J. · Klinische Abteilung für Rheumatologie, Klinik für Innere Medizin 3, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090, Wien, Osterreich. · Z Rheumatol. · Pubmed #19148656 No free full text.

Abstract: Rheumatoid arthritis is a chronic disabling disease that results in considerable loss of physical function in patients over time. The ultimate goal of therapy is remission, a clinical state with a highly variable definition in the literature. For the purpose of achieving the best patient outcome, it is important to maintain the lowest possible disease activity. Therefore, stringent remission criteria should be chosen, which will lead to the best possible prevention of structural and functional decline. Standardised intensive therapeutic strategies and algorithms should form the basis for the administration of anti-rheumatic medication.

Karonitsch T, Aletaha D, Boers M, Bombardieri S, Combe B, Dougados M, Emery P, Felson D, Gomez-Reino J, Keystone E, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Richards P, van Riel P, Siegel J, Smolen JS, Sokka T, van der Heijde D, van Vollenhoven R, Ward M, Wells G, Zink A, Landewe R. · Division of Rheumatology, Medical University of Vienna, Vienna, Austria. · Ann Rheum Dis. · Pubmed #18791056 No free full text.

Abstract: OBJECTIVE: To use an evidence-based and consensus-based approach to elaborate recommendations on how to report disease activity in clinical trials of patients with rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: After an initial expert meeting, during which relevant research questions were identified, a systematic literature search was performed using Medline, Embase and the Cochrane Library as sources. To ensure literature retrieved was comprehensive, we emphasised search algorithms that were sensitive rather than specific. The results of the literature search were discussed by the expert panel, modified and expanded, and were used as the basis for the elaboration of the recommendation in the consensus process. Finally, an independent ACR panel approved these items with some minor modifications. RESULTS: The following pieces of evidence were obtained from the literature search: (1) timing and the sustaining of a response is relevant to achieve better outcomes; (2) composite disease activity indices have been used to define low disease activity and remission and these definitions have been validated as has the American Rheumatism Association (ARA) remission criteria. The "patient-reported symptom state" (PASS) is not yet well validated; (3) evidence was obtained to identify those measures, scales and patient-reported instruments, for which there is a documented association with relevant outcomes; (4) baseline disease activity is associated with disease activity levels at the end of follow-up; and (5) there was not sufficient evidence relating the added benefit of MRI or ultrasound over clinical assessments. Most data stemmed from observational studies rather than clinical trials and literature review was supplemented by input from experts. The results served as the basis for the elaboration of the seven recommendations by the experts. CONCLUSIONS: The approach based on scientific evidence from the literature as well as on expert input provided sufficient information to derive recommendations on reporting disease activity in RA clinical trials. The methodology, results and conclusions of this project were endorsed by EULAR and the ACR.

Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C, Bombardieri S, Choi H, Combe B, Dougados M, Emery P, Gomez-Reino J, Keystone E, Koch G, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Michaud K, O'Dell J, Paulus H, Pincus T, Richards P, Simon L, Siegel J, Smolen JS, Sokka T, Strand V, Tugwell P, van der Heijde D, van Riel P, Vlad S, van Vollenhoven R, Ward M, Weinblatt M, Wells G, White B, Wolfe F, Zhang B, Zink A, Felson D. · Division of Rheumatology, Medical University of Vienna, Vienna, Austria. · Ann Rheum Dis. · Pubmed #18791055 No free full text.

Abstract: OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardised operating procedures, which use a three-step approach: (1) expert-based definition of relevant research questions (November 2006); (2) systematic literature search (November 2006 to May 2007); and (3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature the expert panel recommended that each trial should report the following items: (1) disease activity response and disease activity states; (2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; (3) baseline disease activity levels (in general); (4) the percentage of patients achieving a low disease activity state and remission; (5) time to onset of the primary outcome; (6) sustainability of the primary outcome; (7) fatigue. CONCLUSIONS: These recommendations endorsed by EULAR and ACR will help harmonise the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

Aletaha D, Funovits J, Smolen JS. · Medical University of Vienna, Vienna, Austria. · Arthritis Rheum. · Pubmed #18759299 No free full text.

Abstract: 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.

Smolen JS, Han C, van der Heijde DM, Emery P, Bathon JM, Keystone E, Maini RN, Kalden JR, Aletaha D, Baker D, Han J, Bala M, St Clair EW, Anonymous00041. · Department of Internal Medicine III, Medical University of Vienna, Austria. · Ann Rheum Dis. · Pubmed #18593759 No free full text.

Abstract: OBJECTIVE: To examine the association of radiographic progression and disease activity states in patients with rheumatoid arthritis (RA) treated with methotrexate with or without infliximab. METHODS: Patients (n = 1049) with active RA for 3 years or less and no previous methotrexate treatment were randomly assigned (4 : 5 : 5) to receive methotrexate plus placebo or methotrexate plus infliximab 3 or 6 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter to week 46. Disease activity was classified by the simplified disease activity index as remission (< or =3.3), low (>3.3 to < or =11), moderate (>11 to < or =26), high (>26). Radiographic progression was measured as a change from baseline to week 54 in total Sharp score. RESULTS: At weeks 14 and 54, more patients receiving methotrexate plus infliximab than methotrexate plus placebo were in remission (10.7% versus 2.8% week 14; 21.3% versus 12.3% week 54; p<0.001 for both). Methotrexate plus placebo halted radiographic progression only if patients achieved remission within 3 months, whereas methotrexate plus infliximab also halted or minimised progression in patients with low or moderate activity, respectively. Patients with persistently high disease activity levels had much less progression of joint damage if treated with methotrexate plus infliximab versus methotrexate monotherapy. Even with infliximab plus methotrexate there was a direct relationship between disease activity and radiographic changes, although the slope was deflected when compared with methotrexate monotherapy. CONCLUSION: With methotrexate, joint damage progresses even at low and moderate disease activity levels, whereas methotrexate plus infliximab inhibits radiographic progression across all disease activity states.

Aletaha D, Smolen J. · Department of Internal Medicine 3 at Medical University of Vienna, Austria. · Nat Clin Pract Rheumatol. · Pubmed #18493270 No free full text.

This publication has no abstract.

Wells G, Becker JC, Teng J, Dougados M, Schiff M, Smolen J, Aletaha D, van Riel PL. · Department of Epidemiology and Community Medicine, University of Ottawa, Canada. · Ann Rheum Dis. · Pubmed #18490431 links to  free full text

Abstract: 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.

Wolf J, Kapral T, Grisar J, Stamm T, Koeller M, Smolen JS, Aletaha D. · Second Department of Medicine, Hietzing Hospital, Vienna, Austria. · Clin Exp Rheumatol. · Pubmed #18328156 No free full text.

Abstract: BACKGROUND: Despite low-dose gluco-corticoid (GC) treatment, many patients with rheumatoid arthritis (RA) require additional flare therapy with GC at higher doses. Since low dose GC has been suggested to confer resistance to higher doses, we aimed to assess if resistance was detectable on the clinical level in patients with active RA. METHODS: Eighty-nine patients with active RA (Disease Activity Score 28, DAS28>3.2; mean age 54.5 years, mean duration of RA 9.7 years) were consecutively enrolled into a one-week trial of a total of 250 mg prednisolone. We compared improvement of the DAS28 and the Simplified Disease Activity Index (SDAI) in groups of patients with (n=41) and without (n=48) low-dose GC at baseline (by t-test). In addition, we analyzed changes of all individual core set measures of disease activity using multivariate statistics. RESULTS: All clinical, serological and functional measures improved significantly over one week (p<0.001). Baseline RA activity of patients with and without low-dose GC was on average +/- standard deviation similar among the two groups (DAS28: 4.8+/-1.2 and 4.9+/-1.1; mean SDAI: 26.1+/-14.0 and 25.9+/-13.0, respectively), and likewise there was no difference between the two groups in the final disease activity reached, for both the DAS28 (1.4+/-1.1 vs. 1.1+/-1.0; p=0.14) and the SDAI (11.1+/-13.4 vs. 11.1+/-11.4; p=0.99). Improvement in all individual measures was also not different using a multivariate model (p=0.26). CONCLUSION: Pre-treatment with low-dose GC does not appear to portend GC resistance at least clinically, since the responsiveness to GC boosts is unaffected.

Stamm TA, Aletaha D, Pflugbeil S, Kapral T, Montag K, Machold KP, Smolen JS. · Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. · Clin Exp Rheumatol. · Pubmed #18021511 No free full text.

Abstract: As resources in health care systems become increasingly scarce, rheumatologists may need to provide evidence that their quality of care uses the allocated resources effectively by achieving a good outcome for patients with rheumatoid arthritis (RA). In order to assess quality, it has been recommended in other areas of medicine to gather data according to appropriate outcome measures, preferably in electronic databases, enabling identification of benchmarks to compare the outcome quality of different clinical settings.Available electronic applications commonly comprise a database for data processing and storage, as well as a tool for regularly measuring and following disease activity in individual patients. Access to aggregated data makes it possible to monitor disease activity in individual patients over time in relation to treatment. In addition, electronic applications should allow the extraction of patient data according to special characteristics for analysis. In this way, such electronic applications can provide a central database that can be used for monitoring patients in routine care, case studies or general research, as well as facilitating comparisons of quality of care in different centres or in different countries for reference purposes.

Heiberg T, Kvien TK, Mowinckel P, Aletaha D, Smolen JS, Hagen KB. · Department of Research and Education, Ullevål University Hospital, N- 0407 Oslo, Norway. · Ann Rheum Dis. · Pubmed #17965118 No free full text.

Abstract: BACKGROUND: Established thresholds for low levels of disease activity need to be examined from a patients' perspective. OBJECTIVE: To identify new cut-off points for patients' perception of satisfactory condition (patient acceptable symptom state (PASS)) in composite indices and patient-reported outcomes, and to examine the agreement between the new PASS cut-off points for composite indices and existing thresholds for remission, low and moderate disease activity. METHODS: Patients with rheumatoid arthritis from a treatment register (n = 1496, 72.1% women, mean (SD) age 53.9 (13.5) years, disease duration 7.6 (9.1) years, 28-joint Disease Activity Score (DAS28) 4.98 (1.36)) responded during follow-up (12, 24 and 52 weeks) to a global dichotomised question on satisfactory condition (PASS). New PASS cut-off points were identified with the 75th centile estimation and receiver operating characteristic analyses for a variety of outcome measures, and cut-off points for composite indices were examined for agreement with the low disease activity threshold (1.625) of the Patient Activity Scale (PAS) and thresholds for remission, low and moderate disease activity in DAS28, Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI). RESULTS: New PASS cut-off points for DAS28, SDAI and CDAI were in the moderate range of disease activity, and the cut-off point was 3.56 for PAS. Agreement between thresholds for disease activity levels and the PASS cut-off points was best for low disease activity (accuracy 64.5-74.6), and better for moderate disease activity (accuracy 61.3-67.2) than for remission (accuracy 30.7-45.8). CONCLUSION: The current PASS concept seems to be in the range of moderate disease activity.

Stamm T, Mathis M, Aletaha D, Kloppenburg M, Machold K, Smolen J. · Vienna Medical University, Vienna, Austria. · Arthritis Rheum. · Pubmed #17907208 links to  free full text

Abstract: OBJECTIVE: To determine which self-report instruments best explain hand functioning measured by a generic comprehensive hand function test. METHODS: Six questionnaires currently used in hand osteoarthritis (OA), namely, the Arthritis Impact Measurement Scales 2 Short Form (AIMS2-SF), the Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Cochin scale, the Functional Index of Hand OA (FIHOA), the Health Assessment Questionnaire (HAQ), and the Score for Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (SACRAH), were administered once in 100 patients with hand OA together with the Jebsen-Taylor Hand Function Test (JTHFT). In addition, 3 other hand function tests with short administration time were used: the Moberg Picking-Up Test (MPUT), the Button Test (BT), and grip strength. The Short Form 36 was used to describe health status. The relationship between the instruments and the JTHFT was determined by correlation analyses. RESULTS: AIMS2-SF total scores had the highest raw correlation coefficient to the JTHFT, followed by AIMS2-SF upper body limitation subscale, SACRAH stiffness subscale, and SACRAH total score. If controlled for age, the HAQ had the highest correlation coefficient. Of the 3 short hand function tests, the MPUT showed the highest raw correlation coefficient to the JTHFT; if controlled for age, the BT had the highest correlation coefficient. CONCLUSION: To comprehensively assess hand functioning in patients with hand OA, we recommend using both a self-report instrument used more generally in various arthritides and a self-report instrument specifically developed for hand OA. If a short test is preferred, we recommend using the MPUT or BT.

Aletaha D, Funovits J, Keystone EC, Smolen JS. · Medical University of Vienna, Vienna, Austria. · Arthritis Rheum. · Pubmed #17907167 links to  free full text

Abstract: OBJECTIVE: To assess whether disease activity levels at treatment initiation or during the first 3 months of therapy predict disease activity at 1 year after treatment initiation. METHODS: Pooled patient data from early rheumatoid arthritis (RA) clinical trials (n = 1,342) of methotrexate (MTX), tumor necrosis factor (TNF) inhibitor monotherapy (adalimumab and etanercept), and the combination of the two (adalimumab or infliximab plus MTX) were used for the primary analyses. Pooled data from clinical trials of MTX and of TNF inhibitor plus MTX in late RA (n = 712) were used for validation of the results. Disease activity was primarily assessed using the Simplified Disease Activity Index (SDAI); in addition, we calculated the Disease Activity Score 28-joint assessment (DAS28) and the Clinical Disease Activity Index (CDAI). Associations of disease activity measures at baseline and at 1, 2, 3, and 6 months with disease activity values or disease activity states at 1 year were performed using Spearman's rank correlation, analysis of variance, and diagnostic testing procedures, including receiver operating characteristic (ROC) curve analyses, and probit analysis. RESULTS: Correlations with SDAI values at end point were significant (P < 0.0001) at baseline, and increased to r = approximately 0.6 at 3 months. The area under the ROC curve indicated a high diagnostic test yield with respect to the 1-year outcome (area under the ROC curve approximately 0.8). At all time points, including baseline, the group of patients who achieved remission at 1 year had lower average SDAI values than did those whose disease activity was high at 1 year. The groups achieving low or moderate disease activities at 1 year had SDAI values lying between. Baseline disease activity was less associated with disease activity at the end point for treatment with TNF inhibitor plus MTX, indicating its effectiveness over a broader range of baseline disease activity, but the association with end point disease activity was similar to that in the MTX treatment group at 1 month after treatment initiation. The data were similar when scores on the DAS28 and CDAI were used and were fully validated in the independent cohort of patients with late RA. CONCLUSION: The level of disease activity at baseline and especially during the first 3 months of treatment is significantly related to the level of disease activity at 1 year. Patients who reach a moderate or low disease activity status after 3-6 months of therapy may require switching to alternative therapies. Our findings indicate that intensive and dynamic treatment strategies that include a closer look at disease activity at 3 months in patients with early and late RA is warranted.

Aletaha D, Smolen JS. · Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. · Best Pract Res Clin Rheumatol. · Pubmed #17678828 No free full text.

Abstract: Rheumatoid arthritis (RA) disease activity plays a central role in causing disability both directly and via indirect effects mediated through joint damage, a major sequel of persistent active disease. Evaluation of RA disease activity is therefore important to predict the outcome and effectiveness of therapeutic interventions during follow-up. However, disease activity assessment is among the greatest challenges in the care of patients with RA. We regard measurement of activity as an essential element of following the fate of joint diseases like RA. This evaluation can be facilitated by the use of reduced joint counts and simple indices, such as the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI). These scores are validated outcomes for RA and allow the assessment of: actual disease activity, response to therapy, and achievement of particular states such as remission. The simplicity of these scores enables patients to understand the level of their disease activity, as assessed by the rheumatologist, and to correlate increments and decrements of disease activity directly with all aspects of the disease.

Kapral T, Dernoschnig F, Machold KP, Stamm T, Schoels M, Smolen JS, Aletaha D. · Department of Rheumatology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. · Arthritis Res Ther. · Pubmed #17662115 links to  free full text

Abstract: Current treatment strategies aim to achieve clinical remission in order to prevent the long-term consequences of rheumatoid arthritis (RA). Several composite indices are available to assess remission. All of them include joint counts as the assessment of the major 'organ' involved in RA, but some employ reduced joint counts, such as the 28-joint count, which excludes ankles and feet. The aim of the present study was to determine the relevance of excluding joints of the ankles and feet in the assessment of RA disease activity and remission. Using a longitudinal observational RA dataset, we analyzed 767 patients (80% female, 60% rheumatoid factor-positive), for whom joint counts had been recorded at 2,754 visits. We determined the number of affected joints by the 28-JC and the 32-JC, the latter including ankles and combined metatarso-phalangeal joints (as a block on each side). Several findings were supportive of the validity of the 28-joint count: (a) Absence of joint swelling on the 28-joint scale had a specificity of 98.1% and a positive predictive value (PPV) of 94.1% for the absence of swelling also on the 32-joint scale. For absence of tender joints, the specificity and PPV were 96.1% and 91.7%, respectively. (b) Patients with swollen or tender joints in the 32-JC, despite no joint activity in the 28-JC, were clearly different with regard to other disease activity measures. In particular, the patient global assessment of disease activity was higher in these individuals. Thus, the difference in the joint count was not relevant for composite disease activity assessment. (c) The disease activity score based on 28 joints (DAS28) may reach levels higher than 2.6 in patients with feet swelling since these patients often have other findings that raise DAS28. (d) The frequency of remission did not change when the 28-JC was replaced by 32-JC in the composite indices. (e) The changes in joint activity over time were almost identical in longitudinal analysis. The assessment of the ankles and feet is an important part in the clinical evaluation of patients with RA. However, reduced joint counts are appropriate and valid tools for formal disease activity assessment, such as done in composite indices.

Mierau M, Schoels M, Gonda G, Fuchs J, Aletaha D, Smolen JS. · 2nd Department of Medicine, Hietzing Hospital, Vienna, Austria. · Rheumatology (Oxford). · Pubmed #17341506 links to  free full text

Abstract: OBJECTIVE: Remission constitutes the best achievable state in patients with rheumatoid arthritis. We aimed at evaluating sustained remission in a large cohort of patients followed prospectively in clinical practice and to evaluate available instruments to define remission for their stringency in defining this state. PATIENTS AND METHODS: We analysed remission and sustained remission in 621 patients who had two consecutive and complete clinical observations; the average period between the two visits was 92 days (median; quartiles: 82; 105). Remission was evaluated according to modified ACR (mACR), 28 Joint Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) criteria. Sustained remission was defined as remission at both consecutive visits. Patients were treated with traditional disease- modifying antirheumatic drugs, mainly methotrexate, and partly with biological agents (approximately 11%). RESULTS: Remissions at any one of the two visits were seen in 33.5% of patients by SDAI or CDAI, 42.7% by DAS28, and 38.6% by mACR criteria (P < 0.01). Sustained remission was observed in much lower proportions of patients (between 16.7 and 19.6%, dependent on the instrument). Agreement between classifications of remission by kappa-statistics was very good for SDAI vs CDAI, good for DAS28 vs SDAI or CDAI, and only moderate for mACR vs the three other scores. Residual swollen joints were observed in 15% of patients in DAS28 remission (range 1-9), 6% of patients in mACR remission (range 1-8), but only approximately 5% of patients in CDAI or SDAI remission (range 1-2) (P < 0.01). CONCLUSION: Sustained remission can be observed in 17-20% of patients in clinical practice. CDAI and SDAI remission criteria are more stringent than DAS28 and mACR criteria, since they allow for lesser residual disease activity. Consequently, smaller proportions of patients are classified as in remission by SDAI and CDAI than by DAS28 and mACR criteria. Sustained remission is an achievable goal in clinical practice even with the most stringent of the definitions studied.