Composite Disease Activity Index Research Articles

THU0153 Improvements in disease activity score by baseline status: Pooled analysis of five phase 3 studies with tofacitinib (CP-690,550) in patients with active rheumatoid arthritis

BackgroundTofacitinib (CP-690,550) is a novel, oral Janus kinase inhibitor being investigated as a targeted immunomodulator in rheumatoid arthritis.ObjectivesTo assess efficacy of tofacitinib 5 and 10 mg twice-daily (BID) using disease...

AB0509 Comparative effectiveness of tocilizumab (TCZ) and rituximab (RTM) using different disease activity indices (DAS 28, SDAI and CDAI) in patients with rheumatoid arthritis (RA)

BackgroundHumanized anti-interleukin-6 (IL-6) receptor monoclonal antibody (TCZ) and chimeric monoclonal antibody against CD 20 positive B cells (RTM) are effective and safe preparations for the treatment of RA. Taking into...

FRI0132 A multi-biomarker disease activity score (the vectra DA algorithm score) reflects clinical remission for rheumatoid arthritis (RA) in the best study

BackgroundThe multi-biomarker disease activity (MBDA) score has been reported as a novel composite disease activity index for rheumatoid arthritis (RA). To date, we have reported a good correlation of the...

Clinical and Ultrasound‐Based Composite Disease Activity Indices in Rheumatoid Arthritis: Results From a Multicenter, Randomized Study

To evaluate the metrologic properties of composite disease activity indices in rheumatoid arthritis (RA), utilizing information derived from clinical, gray-scale (GS), and power Doppler (PD) ultrasound examinations, and to assess the classification of patients according to disease activity using such indices. This ancillary study utilized data from a multicenter, prospective, randomized, parallel-group study conducted in subjects with moderate RA randomized to receive etanercept and methotrexate (ETN + MTX) or usual care (various disease-modifying antirheumatic drugs [DMARDs]). In multimodal indices, the 28 swollen joint count was either supplemented or replaced by clinically nonswollen joints in which the presence of synovitis was detected either by GS and/or PD and was calculated according to the Disease Activity Score in 28 joints (DAS28) or the Simplified Disease Activity Index (SDAI). Reliability, external validity, and discriminative capacity were calculated at baseline/screening by intraclass correlation coefficient, Pearson's correlation, and standardized response mean, respectively. Data from 62 patients (mean ± SD age 53.8 ± 13.2 years, mean ± SD disease duration 8.8 ± 7.7 years, mean ± SD disease activity 4.6 ± 0.5 [DAS28] and 20.9 ± 5.9 [SDAI]) were analyzed, with 32 receiving ETN + MTX and 30 receiving DMARDs. The metrologic properties were at least as good for GS- and/or PD-based indices as for their clinical counterparts. Using GS- and PD-supplemented indices, an additional 67.8% and 32.3% of patients (DAS28-derived and SDAI-derived indices, respectively) could be classified as having high disease activity at the screening visit. Multimodal indices incorporating ultrasound and clinical data had similar metrologic properties to their clinical counterparts; certain indices allowed for a significantly larger number of patients to be classified to either high or moderate disease activity at the screening visit.

The development of candidate composite disease activity and responder indices for psoriatic arthritis (GRACE project)

ObjectiveTo develop new composite disease activity indices for psoriatic arthritis (PsA).MethodsData from routine clinic visits at multiple centres were collected in a systematic manner. Data included all domains identified as...

Comparison of composite disease activity indices for rheumatoid arthritis

To evaluate the composite disease activity indices for rheumatoid arthritis (RA), we compared disease activities and the changes therein calculated using the Disease Activity Score based on 28 joint counts using erythrocyte sedimentation rate (DAS28-ESR), DAS28-CRP (C-reactive protein), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) in a cohort of 1,412 patients with RA. The median (1st; 3rd quartile) scores were 4.20 (3.31; 5.14) for DAS28-ESR, 3.44 (2.59; 4.36) for DAS28-CRP, 13.6 (7.49; 21.1) for SDAI, and 12.0 (6.9; 18.9) for CDAI. Absolute scores and their changes were significantly correlated (p < 0.0001) in all combinations among these four disease activity indices; however, their correlations were lower in males than in females. Correlations between disease activity indices and the clinical and acute phase reactant variables were different according to disease activity index, sex and age. A comparison of the number of patients in each disease activity category according to the disease activity indices using kappa-statistics revealed an almost perfect agreement between SDAI and CDAI (κ = 0.871), a moderate agreement between DAS28-ESR and SDAI (κ = 0.415) or CDAI (κ = 0.427), but only fair agreement between DAS28-ESR and DAS28-CRP (κ = 0.329). For the selection of a disease activity index for an evaluation of RA patients, both the convenience and the characteristics of the respective disease activity index should be considered.

Development of a preliminary composite disease activity index in psoriatic arthritis

ObjectivesTo develop a preliminary composite psoriatic disease activity index (CPDAI) for psoriasis and psoriatic arthritis.MethodsFive domains were assessed and specific instruments were employed for each domain to determine the extent...

Comparison of composite disease activity indices for rheumatoid arthritis

To evaluate the composite disease activity indices for rheumatoid arthritis (RA), we compared disease activities and the changes therein calculated using the Disease Activity Score based on 28 joint counts using erythrocyte sedimentation rate (DAS28-ESR), DAS28-CRP (C-reactive protein), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) in a cohort of 1,412 patients with RA. The median (1st; 3rd quartile) scores were 4.20 (3.31; 5.14) for DAS28-ESR, 3.44 (2.59; 4.36) for DAS28-CRP, 13.6 (7.49; 21.1) for SDAI, and 12.0 (6.9; 18.9) for CDAI. Absolute scores and their changes were significantly correlated (p < 0.0001) in all combinations among these four disease activity indices; however, their correlations were lower in males than in females. Correlations between disease activity indices and the clinical and acute phase reactant variables were different according to disease activity index, sex and age. A comparison of the number of patients in each disease activity category according to the disease activity indices using kappa-statistics revealed an almost perfect agreement between SDAI and CDAI (κ = 0.871), a moderate agreement between DAS28-ESR and SDAI (κ = 0.415) or CDAI (κ = 0.427), but only fair agreement between DAS28-ESR and DAS28-CRP (κ = 0.329). For the selection of a disease activity index for an evaluation of RA patients, both the convenience and the characteristics of the respective disease activity index should be considered.

Prognostic evaluation of early rheumatoid arthritis

The progression of rheumatoid arthritis (RA) is quite variable, ranging from very mild or subclinical forms (approx. 10%) to rapidly progressing and debilitating forms (10-15%). The majority of patients present with an intermediate stage with episodes of exacerbation separated by periods of relative inactivity, which evolves to progressive functional losses. To optimise the therapeutic management of early RA it is necessary to perform periodic evaluations of the clinical and laboratory test responses to the treatment instituted, as well as the parameters indicating disease prognosis. Composite measures are frequently used to evaluate the disease activity score (DAS), including the response criteria of the American College of Rheumatology (ACR), the response criteria and the DAS according to the European League Against Rheumatism (EULAR) and the composite indices of disease activity (CIDsA): DAS, the index of disease activity based on 28 joints (DAS 28), the simplified disease activity index (SDAI) and the clinical disease activity index (CDAI). The evaluation of prognosis includes investigation of the absence or occurrence of disease and joint damage remission. Due to the multifaceted nature of RA, no single clinical or laboratory parameter is able to describe satisfactorily the level of inflammatory activity or the disease prognosis at any given time.

Application of the GRAPPA Psoriatic Arthritis Treatment Recommendations in Clinical Practice

Psoriatic disease presents with a complex array of clinical features, including peripheral synovitis and skin psoriasis, but there is also variable involvement of the nail, dactylitis, enthesitis, and spinal disease. Composite assessment of disease activity and response taking into account the impact of the disease as a whole on an individual's health and quality of life is of vital importance. Following an extensive literature review, discussions, and consensus, the Group for Research in Psoriasis and Psoriatic Arthritis (GRAPPA) published guidelines to help clinicians make treatment decisions. The utility of these guidelines in routine clinical practice is further enhanced by incorporating them into a Composite Psoriatic Disease Activity Index (CPDAI). The potential application of the CPDAI in typical psoriatic disease patients is presented and discussed. Validation and possible modification of a composite disease activity and responder index is currently being undertaken by GRAPPA.

On the dynamics of nitrite, nitrate and other biomarkers of nitric oxide production in inflammatory bowel disease

Nitrite and nitrate are frequently used surrogate markers of nitric oxide (NO) production. Using rat models of acute and chronic DSS-induced colitis we examined the applicability of these and other NO-related metabolites, in tissues and blood, for the characterization of inflammatory bowel disease. Global NO dynamics were assessed by simultaneous quantification of nitrite, nitrate, nitroso and nitrosyl species over time in multiple compartments. NO metabolite levels were compared to a composite disease activity index (DAI) and contrasted with measurements of platelet aggregability, ascorbate redox status and the effects of 5-aminosalicylic acid (5-ASA). Nitroso products in the colon and in other organs responded in a manner consistent with the DAI. In contrast, nitrite and nitrate, in both intra- and extravascular compartments, exhibited variations that were not always in step with the DAI. Extravascular nitrite, in particular, demonstrated significant temporal instabilities, ranging from systemic drops to marked increases. The latter was particularly evident after cessation of the inflammatory stimulus and accompanied by profound ascorbate oxidation. Treatment with 5-ASA effectively reversed these fluctuations and the associated oxidative and nitrosative stress. Platelet activation was enhanced in both the acute and chronic model. Our results offer a first glimpse into the systemic nature of DSS-induced inflammation and reveal a greater complexity of NO metabolism than previously envisioned, with a clear dissociation of nitrite from other markers of NO production. The remarkable effectiveness of 5-ASA to abrogate the observed pattern of nitrite instability suggests a hitherto unrecognized role of this molecule in either development or resolution of inflammation. Its possible link to tissue oxygen consumption and the hypoxia that tends to accompany the inflammatory process warrants further investigation.

Response of elderly patients with rheumatoid arthritis to methotrexate or TNF inhibitors compared with younger patients

To compare the efficacy of MTX and MTX+TNF inhibitors (TNFis) in elderly patients with RA with that in patients of younger age. Data from two large, randomized, controlled, double-blind trials in patients with early RA using adalimumab or infliximab+MTX 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. Across all age quartiles, improvement on MTX was similar with respect to changes of composite disease activity indices, assessment of physical function and X-ray progression. Likewise, TNFi+MTX 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. Responsiveness of elderly patients with RA to MTX or TNFi+MTX is similar to that observed in patients of younger age.

Which Measure of Inflammation to Use? A Comparison of Erythrocyte Sedimentation Rate and C-Reactive Protein Measurements from Randomized Clinical Trials of Golimumab in Rheumatoid Arthritis

To assess clinical utility of measurements of C-reactive protein (CRP) versus Westergren erythrocyte sedimentation rate (ESR) in evaluating patients with rheumatoid arthritis (RA). Data from 3 randomized clinical trials of golimumab involving 1247 patients with RA in which ESR and CRP were obtained at baseline and Week 24, along with standard measures of clinical disease activity [swollen and tender joint counts, global disease activity assessment, composite Disease Activity Scores (DAS) and Clinical Disease Activity Index (CDAI)], were utilized. Result. Both ESR and CRP were significant predictors of swollen joint count (p < 0.001 for each). Only 4.5% of patients with no swollen joints had elevated CRP and normal ESR, but 15.2% had elevated ESR and normal CRP. ESR and CRP correlated significantly (Pearson r = 0.59, p < 0.001) with each other. DAS-ESR and DAS-CRP were highly correlated (r = 0.96, p < 0.001) with each other, although DAS-ESR values were slightly lower than the DAS-CRP values at the upper end of the range (DAS > 8). Both ESR and CRP were significantly associated with CDAI (p < 0.001 for each). It is not necessary to obtain both ESR and CRP measures for clinical disease activity assessment in clinical trials of RA. Neither test adds significantly to clinical measures of disease activity including joint counts and global assessments. Where available, the CRP alone may be preferred for disease activity assessment as a simple, validated, reproducible, non age-dependent test.

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

BackgroundMost 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.MethodsAgreement 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.ResultsAgreement 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.ConclusionDisease 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.

Drs. Neogi and Felson reply

We thank Dr. Kirwan for his insightful comments regarding potential concerns about relying on a physician global assessment for rheumatoid arthritis (RA) disease activity assessment. We agree that “which physician” is providing his/her global assessment is an important determinant of the validity and reliability of such an outcome. While we advocated the use of composite indices of disease activity over individual core … Address reprint requests to Dr. Neogi.

Developments in the clinical understanding of rheumatoid arthritis.

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.

Methods of deriving EULAR/ACR recommendations on reporting disease activity in clinical trials of patients with rheumatoid arthritis

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...

Acute phase reactants add little to composite disease activity indices for rheumatoid arthritis: validation of a clinical activity score

IntroductionFrequent assessments of rheumatoid arthritis (RA) disease activity allow timely adaptation of therapy, which is essential in preventing disease progression. However, values of acute phase reactants (APRs) are needed to calculate current composite activity indices, such as the Disease Activity Score (DAS)28, the DAS28-CRP (i.e. the DAS28 using C-reactive protein instead of erythrocyte sedimentation rate) and the Simplified Disease Activity Index (SDAI). We hypothesized that APRs make limited contribution to the SDAI, and that an SDAI-modification eliminating APRs – termed the Clinical Disease Activity Index (CDAI; i.e. the sum of tender and swollen joint counts [28 joints] and patient and physician global assessments [in cm]) – would have comparable validity in clinical cohorts.MethodData sources comprised an observational cohort of 767 RA patients (average disease duration 8.1 ± 10.6 years), and an independent inception cohort of 106 patients (disease duration 11.5 ± 12.5 weeks) who were followed prospectively.ResultsOur clinically based hypothesis was statistically supported: APRs accounted only for 15% of the DAS28, and for 5% of the SDAI and the DAS28-CRP. In both cohorts the CDAI correlated strongly with DAS28 (R = 0.89–0.90) and comparably to the correlation of SDAI with DAS28 (R = 0.90–0.91). In additional analyses, the CDAI when compared to the SDAI and the DAS28 agreed with a weighted kappa of 0.70 and 0.79, respectively, and comparably to the agreement between DAS28 and DAS28-CRP. All three scores correlated similarly with Health Assessment Questionnaire (HAQ) scores (R = 0.45–0.47). The average changes in all scores were greater in patients with better American College of Rheumatology response (P < 0.0001, analysis of variance; discriminant validity). All scores exhibited similar correlations with radiological progression (construct validity) over 3 years (R = 0.54–0.58; P < 0.0001).ConclusionAPRs add little information on top (and independent) of the combination of clinical variables included in the SDAI. A purely clinical score is a valid measure of disease activity and will have its greatest merits in clinical practice rather than research, where APRs are usually always available. The CDAI may facilitate immediate and consistent treatment decisions and help to improve patient outcomes in the longer term.

Monoclonal anti‐TNFα Antibody as a Probe of Pathogenesis and Therapy of Rheumatoid Disease

Rheumatoid arthritis is a common cause of chronic disability for which current therapies are of limited value in controlling the disease process and outcome. Our initial approach to understanding the pathogenesis of RA and defining a novel therapeutic target was to investigate the role of cytokines by blocking their action with antibodies on cultured synovial-derived mononuclear cells in vitro. These investigations suggested that neutralization of TNF alpha with antibodies significantly inhibited the generation of other pro-inflammatory cytokines also over-produced, such as, IL-1, GM-CSF, IL-6 and IL-8. The implication that blockade of a single cytokine, TNF alpha might have far-reaching effects on multiple cytokines and thereby exert significant anti-inflammatory and protective effects on cartilage and bone of joints, was tested in arthritic DBA/1 mice immunized with collagen II. Impressive amelioration of joint swelling and joint erosions in this model encouraged clinical trials with a monoclonal anti-TNF alpha antibody. The cA2 chimeric anti-TNF alpha high-affinity antibody was initially tested in an open-label study at a dose of 20 mg/kg on 20 patients, with substantial and universal benefit. Subsequently, a randomized placebo-controlled double-blind trial was performed on 73 patients comparing a single intravenous injection of placebo (0.1% human serum albumin) with two doses of cA2. Using a composite disease activity index, at 4 weeks post infusion, 8% of patients receiving placebo improved compared with 44% receiving 1 mg/kg cA/2 and 79% receiving 10 mg/kg. Between 2 to 4 repeated cycles of cA2 were administered to 7 patients and all patients showed improvement of a similar magnitude with each cycle. These data support our proposition that TNF alpha is implicated in the pathogenesis of RA, and is thus a key therapeutic target. Monoclonal anti-TNF alpha antibodies control disease flares and are candidate agents for longer-term control of RA, although repeated therapy with cA2 is associated with anti-idiotypic responses in 50% of patients and a trend toward shortening of the duration of response. In the DBA/1 arthritic mice, synergy of action of anti-TNF and anti-CD4 is observed together with suppression of an anti-globulin response, indicating one way in which benefit might be augmented in the future.