RAPID3 (Routine Assessment of Patient Index Data) on an MDHAQ (Multidimensional Health Assessment Questionnaire): Agreement with DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index) activity categories,scored in five versus more than ninety seconds

Objective

To compare the Routine Assessment of Patient Index Data 3 (RAPID3) on a Multidimensional Health Assessment Questionnaire (MDHAQ) with the Disease Activity Score (DAS28), Clinical Disease Activity Index (CDAI), and individual core data set measures for correlations, agreement of activity levels, and time to score.

Methods

Four rheumatologists each assessed 50 patients with rheumatoid arthritis in “real‐time” clinical care. Patients completed an MDHAQ. The rheumatologist then calculated RAPID3 (physical function, pain, patient global estimate), performed a 28‐joint count, assigned a physician global estimate, and scored a CDAI, each timed by an observer. Erythrocyte sedimentation rate (ESR) was tested on the same date, and the DAS28‐ESR was computed later, again timed by an observer. Spearman's rank‐order correlations and comparisons of patients classified as high activity, moderate activity, low activity, and remission according to the DAS28, CDAI, and RAPID3 were computed and compared with kappa statistics. A second study of 25 “paper patients” was also performed to compare time to score the DAS28, CDAI, and RAPID3 on a 0–10 versus 0–30 scale. Mean and median times to score each index were computed.

Results

The 3 indices were correlated significantly, including agreement for >80% of patients for high/moderate activity. The mean time to perform a 28‐joint count was 94 seconds, and the mean times to score the DAS28, CDAI, RAPID3 on a 0–10 scale, and RAPID3 on a 0–30 scale were 114, 106, 9.6, and 4.6 seconds, respectively.

Conclusion

RAPID3 scores provide similar quantitative information to DAS28 and CDAI, while calculated on a 0–30 scale in about 5% of the time.     

Validation of RAPID3 using a Japanese version of Multidimensional Health Assessment Questionnaire with Japanese rheumatoid arthritis patients: Characteristics of RAPID3 compared to DAS28 and CDAI

Abstract

Objectives. To validate Routine Assessment of Patient Index Data 3 (RAPID3) using a Japanese version of Multidimensional Health Assessment Questionnaire (MDHAQ) with Japanese rheumatoid arthritis (RA) patients and to describe the characteristics of RAPID3 by comparison with Disease Activity Score 28 (DAS28) and Clinical Disease Activity Index (CDAI).

Methods. The original MDHAQ was translated into Japanese with minor cultural modifications and was translated back in English. Test–retest reliability was evaluated in 50 Japanese RA patients and further validation was performed in 350 Japanese RA patients recruited by seven rheumatologists. RAPID3, CDAI, and DAS28 were assessed on two consecutive visits.

Results. The test–retest reliability and the internal reliability of RAPID3 were excellent. Spearman's correlation coefficients between RAPID3 score versus CDAI score and DAS28 score were 0.761and 0.555. However, the agreement measured by kappa (weighted) for RAPID3 category versus CDAI category and for RAPID3 category versus DA28 category were 0.225 (0.382) and 0.187 (0.336). The sensitivity and specificity of “RAPID3 ≤ 3 and swollen joint ≤ 1” for predicting Boolean remission were 90.0% and 93.4%, respectively.

Conclusions. RAPID3 obtained by Japanese MDHAQ was validated with Japanese RA patients and the remission criteria were found to have excellent clinical utility in usual care.     

RAPID3 (Routine Assessment of Patient Index Data 3) severity categories and response criteria: Similar results to DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index) in the RAPID 1 (Rheumatoid Arthritis Prevention of Structural Damage) clinical trial of certolizumab pegol

Objective

To compare categories for activity/severity according to the Disease Activity Score 28‐joint count (DAS28), the Clinical Disease Activity Index (CDAI), and the Routine Assessment of Patient Index Data 3 (RAPID3), an index without formal joint counts calculated in 5 versus >100 seconds, as well as the European League Against Rheumatism (EULAR)– DAS28 and the RAPID3 response criteria, in the Rheumatoid Arthritis Prevention of Structural Damage (RAPID 1) clinical trial of certolizumab pegol (CZP).

Methods

Post hoc analyses were performed using correlations, cross‐tabulations, and kappa statistics. Patients (treated with CZP plus methotrexate [MTX] or placebo plus MTX) were classified at baseline and at 52 weeks as high, moderate, low activity/severity or remission, according to the DAS28 (>5.1, >3.2 to ≤5.1, 2.6 to ≤3.2, <2.6 [total range 0–10]), the CDAI (>22, >10 to ≤22, >2.8 to ≤10, ≤2.8 [total range 0–76]), and RAPID3 (>12, >6 to ≤12, >3 to ≤6, ≤3 [total range 0–30]), as well as for good, moderate, and poor EULAR‐DAS28 and proposed RAPID3 response criteria.

Results

All measures were correlated significantly: RAPID3 with DAS28 and CDAI (rho > 0.7), higher than erythrocyte sedimentation rate with C‐reactive protein level (rho = 0.47). At 52 weeks, DAS28, CDAI, and RAPID3 low activity/remission was seen in 30%, 44%, and 42% of CZP‐treated patients versus 3%, 7%, and 10% of control patients. Good, moderate, and poor EULAR‐DAS28 responses were seen in 30%, 51%, and 19% of CZP‐treated patients versus 3%, 28%, and 70% of control patients, and for RAPID3 in 39%, 30%, and 32% of CZP‐treated patients versus 8%, 16%, and 76% of control patients. Kappa and weighted kappa values ranged from 0.36–0.53, indicating fair to moderate agreement.

Conclusion

RAPID3, DAS28, and CDAI give similar results to distinguish CZP patients from controls in the RAPID 1 clinical trial. DAS28 is specific for clinical trials; RAPID3 appears pragmatically useful for usual care.     

Performance of Routine Assessment of Patient Index Data 3 (RAPID3) for assessment of rheumatoid arthritis in clinical practice: differential agreement of RAPID3 according to disease activity categories

To evaluate the performance of Routine Assessment of Patient Index Data 3 (RAPID3) with the disease activity score 28 (DAS28) and the clinical/simplified disease activity index (CDAI/SDAI) in a Korean population with rheumatoid arthritis (RA). Four hundred patients with RA were consecutively enrolled. All patients completed disease activity indices such as RAPID3, DAS28, SDAI, and CDAI. The kappa and/or weighted coefficients were used to assess agreement between RAPID3 and other disease activity indices. ANOVA, Mantel–Haenszel chi-square test, and Spearman’s partial correlation analysis were used for analyses. RAPID3 scores were significantly correlated with DAS28 (r = 0.62), SDAI (r = 0.74), and CDAI (r = 0.75; p < 0.0001 for all indices) and other activity measures including swollen/tender joint counts, erythrocyte sediment rate, and C-reactive protein. The weighted kappa coefficients of RAPID3 with DAS28, SDAI, and CDAI among the four disease activity categories were 0.33, 0.34, and 0.33, respectively. Kappa coefficients for RAPID3 in two disease activity categories increased more than four categories (κ = 0.40–0.42) indicating fair agreement. More than 86 % of patients with high-to-moderate disease activity in DAS28, CDAI, and SDAI had high-to-moderate disease activity using RAPID3 criteria. However, approximately 50 % of patients with remission-to-low disease activity in DAS28, CDAI, and SDAI showed remission-to-low disease activity in RAPID3. This study confirms RAPID3 as an informative disease activity index with equivalent values in DAS28, CDAI, and SDAI. RAPID3 reveals differential agreement in patients with lower disease activity.     

Time to score quantitative rheumatoid arthritis measures: 28-Joint Count, Disease Activity Score, Health Assessment Questionnaire (HAQ), Multidimensional HAQ (MDHAQ), and Routine Assessment of Patient Index Data (RAPID) scores

OBJECTIVE: To analyze the time required to score different measures used to assess patients with rheumatoid arthritis (RA), as a guide to feasibility in standard care. The measures studied were a 28-Joint Count, Disease Activity Score (DAS), Health Assessment Questionnaire (HAQ), Multidimensional HAQ (MDHAQ), and various Routine Assessment of Patient Index Data (RAPID) scores derived from the MDHAQ. METHODS: Three rheumatologists at 3 sites performed and timed 28-joint counts in 20 different patients at each site. Each rheumatologist scored and timed identical data in 5 groups of 10 from the same 50 patients seen in standard clinical care, including 50 DAS28 indices using the DAS Website, 50 identical HAQ, and 50 identical MDHAQ from the same patients. The MDHAQ includes 10 activities self-assessed for physical function, 21 circle visual analog scales (VAS) (rather than 10 cm lines), and scoring templates on the questionnaire for physical function, patient self-report joint count and RAPID composite scores. RAPID3 includes the 3 Core Data Set measures, RAPID4 adds the self-report joint count to RAPID3, and RAPID5 adds a physician global estimate to RAPID4. RESULTS: The median number of seconds to complete a 28-joint count was 90, compared to 41.9 s for a HAQ, 9.6 s for an MDHAQ RAPID3, and 19.4 s for RAPID5. CONCLUSION: MDHAQ RAPID3 scores can be calculated in considerably less time than other RA measures, using scoring templates on the MDHAQ, to provide informative, feasible, quantitative measures for standard rheumatology clinical care.     

Reexamination of the assessment criteria for rheumatoid arthritis disease activity based on comparison of the Disease Activity Score 28 with other simpler assessment methods

Objective

To explore simpler and possibly more appropriate tools than the conventional Disease Activity Score 28 (DAS28) for assessing rheumatoid arthritis (RA) and to derive more reliable DAS28-based criteria.

Methods

The capabilities of assessing disease activities in 250 RA patients were compared between DAS28 and other methods, including the Simplified DA Index (SDAI), Clinical DA Index (CDAI), and Routine Assessment of Patient Index Data-3 (RAPID-3).

Results

SDAI and CDAI showed a good correlation and consistency with DAS28, whereas RAPID-3 yielded inferior results. In terms of remission criteria, DAS28 was less stringent than SDAI or CDAI; when RA remission was reexamined based on more stringent SDAI or CDAI criteria, cut-off values for DAS28-C-reactive protein of <1.72 were considered to be appropriate. The conventional DAS28 was considered to be appropriate for assessing low, middle and high disease activities because it provides criteria similar to or more stringent than those of other methods, while SDAI and CDAI were considered to be simpler and more appropriate criteria for assessing remission.

Conclusion

For assessing remission, DAS28-CRP provides the most appropriate criterion of the methods compared when the currently used cut-off value of 2.3 is lowered to a new value of 1.72.     

Correlation between rapid-3, DAS28, CDAI and SDAI as a measure of disease activity in a cohort of Colombian patients with rheumatoid arthritis

The objective of this study is to correlate the patient-driven tool Routine Assessment of Patient Index Data 3 (RAPID-3) with other common tools used in daily practice to measure disease activity in rheumatoid arthritis (RA).One hundred nineteen RA patients according to 1987 American College of Rheumatology criteria who consecutively attended a RA outpatient clinic between August and December 2015 were evaluated. Data was stored in an electronic form that included demographic information, comorbidities, concomitant medication, and laboratory results. The disease activity was determined by tender and swollen joint count, pain and disease activity visual analog scales (VAS), disease activity score 28 (DAS28), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and multidimensional health assessment questionnaire (MDHAQ). Correlations between RAPID-3 and other disease activity tools were assessed. Mean age was 61 ± 13.8 years with a median disease duration of 14 years (IQR 5–21), 77% were females. Median scores were MDHAQ 0.5 (IQR 0.1–1.2), DAS 28 3.8 (IQR 2.7–5.1), and RAPID-3 12.3 (IQR 6–19). A strong correlation was obtained between RAPID-3 and DAS 28 (r 0.719, p < 0.001), CDAI (r 0.752, p < 0.001), and SDAI (r 0.758, p < 0.001). RAPID-3 had a high correlation with tools regularly used for disease activity assessment of RA patients in daily practice. The ease of its application favors routine use as it does not require laboratory results and joint counts.     

Value of Disease Activity Score 28 (DAS28) and DAS28-3 compared to American College of Rheumatology-defined remission in rheumatoid arthritis

OBJECTIVE: To assess the criteria for remission based on Disease Activity Score 28 (DAS28) and DAS28-3 (excluding patients' evaluation of disease activity) compared to American College of Rheumatology (ACR) preliminary criteria in established rheumatoid arthritis (RA), and to examine the value of each ACR criterion individually. METHODS: The EMECAR study was designed to assess the burden of comorbidity and inflammatory activity for RA in Spain. A random sample of 788 patients with RA from 34 Spanish centers was selected. Remission was defined by preliminary ACR criteria applied specifically and the clinical activity assessed by the DAS28 and the DAS28-3. A receiver operating characteristics curve analysis was performed to identify cutoff values with the highest usefulness in defining remission on both DAS indices. RESULTS: Thirty-two patients (4.1%) were in ACR-defined remission, 62 (7.9%) if fatigue was excluded from the criteria. The frequency of any single criterion that patients in remission fulfilled: no fatigue and joint pain by anamnesis in 31 patients (96.9%); morning stiffness < 15 min in 26 (81.3%); no swelling in joints in 21 (65.6%); normal erythrocyte sedimentation rate (ESR) in 29 (90.6%); and no joint tenderness in 21 (65.6%) patients. The positive predictive value for remission of each criterion: normal ESR 6.5%; morning stiffness < 15 min 8.4%; no fatigue 8.7%; no joint tenderness 13%; no swelling in joints 15.8%; and no joint pain by anamnesis 27.7%. The DAS28 cutoff values with higher discriminatory power for remission were 3.14 (sensitivity 87%; specificity 67%) when all the ACR criteria were used, and 2.81 (sensitivity 84%; specificity 81%) when fatigue was omitted. The equivalent cutoffs for the DAS28-3 were 3.52 (sensitivity 84%; specificity 66%) and 2.95 (sensitivity 82%; specificity 83%), respectively. CONCLUSION: DAS28 and DAS28-3 are good tools to define remission in established RA. No joint pain by anamnesis is the criterion with the highest value in defining remission, while normal ESR, an absence of morning stiffness, and fatigue are the least effective.     

A proposed continuous quality improvement approach to assessment and management of patients with rheumatoid arthritis without formal joint counts, based on quantitative routine assessment of patient index data (RAPID) scores on a multidimensional health assessment questionnaire (MDHAQ)

A continuous quality improvement approach is proposed for the assessment and management of patients with rheumatoid arthritis (RA) based on scores on a one-page patient self-report multidimensional health assessment questionnaire (MDHAQ), without formal joint counts. The approach includes five simple steps before the patient is seen by the physician: (1) an MDHAQ is completed by every patient at every visit; (2) scores are calculated for patient function, pain, and global estimate, with options for a self-report joint count and other scales; (3) scores are entered on flow sheets with data from prior visits, which might also include laboratory and medication information; (4) scores are compiled into an index termed Routine Assessment of Patient Index Data (RAPID), analogous to a Disease Activity Score (DAS); (5) RAPID scores are classified to guide treatment decisions. RAPID 3 includes the three patient-reported outcome (PRO) measures in the RA Core Data Set - physical function, pain, and global estimate. RAPID 4 adds a self-report joint count, and RAPID 5, a physician global estimate. RAPID 3 can be calculated in about 10 seconds, RAPID 4 in about 19 seconds, and RAPID 5 in about 20 seconds. RAPID 3, RAPID 4, and RAPID 5 give similar results to distinguish active from control treatments in RA clinical trials, at levels similar to American College of Rheumatology or DAS improvement criteria, and are all correlated significantly with DAS28 (rho=0.62-0.64, P<0.001). A proposed classification of RAPID scores, analogous to four DAS28 categories, includes: 'near remission' (0-1), 'low severity' (1.01-2), 'moderate severity' (2.01-4), and 'high severity' (>4). RAPID scoring is feasible in standard clinical care to support continuous quality improvement.     

Revising DAS28 scores for remission in rheumatoid arthritis

Current initiatives to treat rheumatoid arthritis (RA) to target remission have resulted in the widespread use of composite outcome measures to quantify disease activity. Simplified Disease Activity Index (SDAI) ≤3.3 is the gold standard of remission. Previous work has suggested that the remission threshold of DAS28-ESR or DAS28-CRP ≤2.6 is known to be not strict enough and should be revised. There is no previous study that looks at the equivalent DAS28-CRP value that best reflects SDAI remission in a real-life cohort. Consecutive cases fulfilling ACR/EULAR classification criteria for RA from one centre were included if they had an optimum number of visits with recording of all raw data to calculate DAS28-ESR, DAS28-CRP and SDAI. Data from seven visits each of 76 patients, providing 532 data points was examined. Spearman’s correlation between DAS28-ESR, DAS28-CRP and SDAI was 0.91–0.97 (p?<?0.001). A Bland-Altman plot demonstrated a mean difference of 0.37 units between DAS28-ESR and DAS28-CRP (p?<?0.001). ROC and kappa analysis provided values of 2.58 and 2.55 for DAS28-ESR4V and 2.09 and 2.05 for DAS28-CRP4V for SDAI value of 3.3, respectively. The two versions of DAS28 using ESR and CRP and SDAI correlate but are not equivalent or interchangeable for an individual patient. The DAS28-CRP overestimates remission and should be revised downwards to a proposed value of 2.1.     

Visualization of DAS28, SDAI,and CDAI: the magic carpets of rheumatoid arthritis

There has been continuous debate regarding the applicability of various composite measures for the assessment of disease activity in rheumatoid arthritis (RA). In order to further dissect this issue, we numerically and graphically modeled 28-joint disease activity scale (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI) by three-dimensional (3D) plotting. We wished to graphically visualize the relative contribution of various elements in the three activity indices to each other. We calculated DAS28 (3 variables), SDAI, and CDAI by the standard equations. We plotted 3D “carpets” showing all combinations of the corresponding variables yielding to DAS28?=?5.1, DAS28?=?3.2, DAS28?=?2.6, SDAI?=?26, SDAI?=?11, and SDAI?=?3.3. We also plotted the 3D carpet for CDAI. In patients with high or moderate disease activity, erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) was not a major confounding factor when calculating DAS28 and SDAI, respectively. In contrast, ESR and CRP highly overshadowed changes in joint counts and global assessments in patients with low disease activity (LDA) or those in remission. No reliable assessment of LDA can be performed in cases where ESR >54 mm/h or CRP >20 mg/dl. Similarly, remission cannot be determined if ESR >19 mm/h or CRP >5 mg/dl. As CDAI does not include acute phase reactants, CDAI may be a useful tool even in states of remission or LDA. Our results suggest that acute phase reactants are indeed major confounding factors and should be omitted when assessing RA disease activity at least in special cases.     

Assessment of the validity of the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) as a disease activity index of rheumatoid arthritis in the efficacy evaluation of 24-week treatment with tocilizumab: subanalysis of the SATORI study

As tocilizumab (TCZ) greatly inhibits inflammatory markers, methods of evaluating rheumatoid arthritis (RA) disease activity that include inflammatory markers may overestimate the effect of TCZ treatment. We have evaluated the impact of inflammatory markers on the efficacy of TCZ by comparing the efficacy indicated by the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) with that indicated by the clinical and simplified disease activity indexes (CDAI and SDAI, respectively) and the American College of Rheumatology (ACR) core set criteria in a double-blind study of TCZ—the SATORI study. The Spearman correlation coefficient between DAS28-ESR and CDAI was comparable between that at week 24 and that at baseline [correlation coefficient at baseline and week 24 was 0.823 (p < 0.0001) and 0.818 (p < 0.0001), respectively]. A large difference between the DAS28 remission rate and CDAI remission rate was observed at week 24. However, these results are comparable to those of a previous study conducted with non-TCZ-treated patients. Moreover, the same results were obtained in the comparison between the DAS28-ESR and SDAI, even though the SDAI includes an inflammatory parameter as a component. These results confirm that the DAS28-ESR has a validity comparable to that of other methods in terms of evaluating the RA treatment efficacy of TCZ, despite its strong inflammatory marker-inhibiting effects.     

Assessment of the validity of the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) as a disease activity index of rheumatoid arthritis in the efficacy evaluation of 24-week treatment with tocilizumab: subanalysis of the SATORI study

Abstract

As tocilizumab (TCZ) greatly inhibits inflammatory markers, methods of evaluating rheumatoid arthritis (RA) disease activity that include inflammatory markers may overestimate the effect of TCZ treatment. We have evaluated the impact of inflammatory markers on the efficacy of TCZ by comparing the efficacy indicated by the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) with that indicated by the clinical and simplified disease activity indexes (CDAI and SDAI, respectively) and the American College of Rheumatology (ACR) core set criteria in a double-blind study of TCZ—the SATORI study. The Spearman correlation coefficient between DAS28-ESR and CDAI was comparable between that at week 24 and that at baseline [correlation coefficient at baseline and week 24 was 0.823 (p < 0.0001) and 0.818 (p < 0.0001), respectively]. A large difference between the DAS28 remission rate and CDAI remission rate was observed at week 24. However, these results are comparable to those of a previous study conducted with non-TCZ-treated patients. Moreover, the same results were obtained in the comparison between the DAS28-ESR and SDAI, even though the SDAI includes an inflammatory parameter as a component. These results confirm that the DAS28-ESR has a validity comparable to that of other methods in terms of evaluating the RA treatment efficacy of TCZ, despite its strong inflammatory marker-inhibiting effects.     

Interleukin‐6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: The role of acute‐phase reactants

Objective

To determine the effects of tocilizumab on rheumatoid arthritis (RA) disease activity and remission assessment, using measures that do or do not comprise acute‐phase reactants.

Methods

Simplified Disease Activity Index (SDAI) scores, Clinical Disease Activity Index (CDAI) scores, and the Disease Activity Score in 28 joints (DAS28) were calculated using data from tocilizumab trials in patients with RA in whom disease had remained active despite treatment with disease‐modifying antirheumatic drugs. The CDAI does not contain an acute‐phase reactant component. Disease activity states, including remission, were defined using established cut points; for the DAS28, an alternative cut point of <2.4 was also used.

Results

Changes in the DAS28, the SDAI score, and the CDAI score among patients receiving tocilizumab were significantly higher than those among patients receiving placebo, and the magnitude of these changes was similar for the SDAI and the CDAI. Among patients who achieved 50% improvement in disease activity according to the American College of Rheumatology criteria, only ∼20% required a reduction in acute‐phase reactant values in order to fulfill the criteria. However, DAS28 remission rates were higher (even when using the lower cut point) than the SDAI and CDAI remission rates. Only a minority of tocilizumab‐treated patients with DAS28 remission also had disease remission according to the SDAI (26%) or CDAI (∼21%). With infliximab treatment, SDAI and CDAI remission rates were of the same magnitude as those observed with tocilizumab treatment, and DAS28 remission rates were lower. Tocilizumab‐treated patients with DAS28 remission but without CDAI remission had significantly higher swollen joint counts but lower erythrocyte sedimentation rates (ESRs) compared with patients with SDAI or CDAI remission.

Conclusion

Disease activity in RA is reduced by tocilizumab treatment, irrespective of the type of composite measure used to evaluate disease activity. Remission rates were much higher using the DAS28 compared with the SDAI and CDAI, due to the high weight of the ESR in the DAS28 and the effect of tocilizumab on the ESR. Using the stringent SDAI and CDAI criteria, however, remission rates in patients treated with tocilizumab were in the same range as those seen in patients treated with tumor necrosis factor inhibitors.

     

Remission and rheumatoid arthritis: data on patients receiving usual care in twenty-four countries

OBJECTIVE: To compare the performance of different definitions of remission in a large multinational cross-sectional cohort of patients with rheumatoid arthritis (RA). METHODS: The Questionnaires in Standard Monitoring of Patients with RA (QUEST-RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4-page self-report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self-report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission). RESULTS: The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was >/=15% in 10 countries, 5-14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission. CONCLUSION: The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.     

Evaluation of disease activity in patients with rheumatoid arthritis treated with tofacitinib by RAPID3: post hoc analyses from two phase 3 trials

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. We evaluated the relationship between disease activity, according to Routine Assessment of Patient Index Data 3 (RAPID3) after 6-month treatment with tofacitinib, and long-term outcomes at 24 months. This was a post hoc analysis of two 24-month, phase 3, randomized controlled trials in methotrexate (MTX)-naïve (ORAL Start [NCT01039688]) or MTX-inadequate responder patients (ORAL Scan [NCT00847613]) receiving tofacitinib 5 or 10 mg twice daily (BID) as monotherapy or with background MTX. RAPID3 scores were calculated at baseline, month (M)6, and M24, and defined as remission (≤?3), low (LDA; >?3–≤?6), moderate (MDA; >?6–≤?12), or high disease activity (HDA; >?12). Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, and radiographic non-progression (modified Total Sharp Scores ≤?0) at M24 were evaluated by M6 RAPID3 response. Among patients receiving tofacitinib 5 or 10 mg BID, respectively, 42.2 and 51.5% (ORAL Start) and 29.8 and 39.0% (ORAL Scan) achieved RAPID3 remission/LDA at M6. Most patients maintained/improved RAPID3 responses at M24. A higher proportion of patients in RAPID3 remission/LDA versus MDA/HDA at M6 achieved CDAI remission, reported normative HAQ-DI scores (<?0.5), and achieved both normative HAQ-DI scores and radiographic non-progression at M24. Patients achieving RAPID3 remission/LDA after 6-month treatment with tofacitinib 5 or 10 mg BID have improved long-term outcomes versus patients with MDA/HDA. These findings support the use of RAPID3 to monitor longer-term disease activity in conjunction with physician-assessed measures.     

Comparative validation of clinical disease activity index (CDAI) and simplified disease activity index (SDAI) in rheumatoid arthritis in India

BackgroundCDAI and SDAI have been frequently used to categorize disease activity in patients with rheumatoid arthritis (RA), but have not been comparatively validated in Indian population.ObjectiveTo validate CDAI and SDAI in RA, taking DAS-28 as gold standard and to derive new cutoffs for CDAI and SDAI.MethodsPatients fulfilling ACR/EULAR criteria for diagnosis of RA were studied. After complete history, physical examination and biochemical tests, patients were grouped into remission, low, moderate and high activity on the basis of pre-defined cut-offs for DAS-28, CDAI, and SDAI. Spearman’s correlation and group wise inter-rater agreement tests were performed. Using DAS-28 as gold standard, the sensitivity and specificity of CDAI and SDAI cut off were determined for predicting levels of disease activity by area under receiver operator characteristics curves. (AUROC)ResultsWe studied 112 patients with RA, there was excellent correlation between DAS-28 and CDAI (r = 0.96 with 95% C.I. = 0.94?0.97), CDAI and SDAI (r=0.99, 95% C.I. 0.98?1), and DAS-28 and SDAI (r = 0.96, 95% C.I. = 0.94?0.97). There was a good inter-rater agreement between the various levels of disease activity as defined by DAS-28 and CDAI (weighed k = 0.598) and DAS-28 and SDAI (weighed k = 0.699) with excellent agreement between SDAI and CDAI categories (weighed k = 0.816). There was no statistically significant difference between AUROC of CDAI and SDAI and both performed equally well.ConclusionCDAI and SDAI are highly correlated with DAS-28 score hence are good markers of disease activity. The cut-off values for CDAI and SDAI used in western literature can be used with minor modifications in Indian scenario.     

Test–retest reliability of the Disease Activity Score 28 CRP (DAS28-CRP), the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) in rheumatoid arthritis when based on patient self-assessment of tender and swollen joints

Composite disease activity scores are frequently used in daily practice as tools for treatment decisions in patients with rheumatoid arthritis (RA). If reliable, patient-reported disease activity may be time saving in the busy clinic. The objective was to examine the test–retest reliability of the Disease Activity Score 28 CRP (DAS28-CRP) with four variables (4v) and three variables (3v), the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) when based on patient self-assessment of tender and swollen joints and to examine the agreement between these scores and physician-derived scores. Thirty out-clinic RA patients with stable disease were included. A joint count was performed two times 1 week apart by the patient and by an experienced physician. Test–retest reliability was expressed as the least significant difference (LSD), as the LSD in percent of the mean score (%LSD) and as intra-individual coefficients of variation (CV_i). Mean scores based on physician vs. patient joint counts (visit 1) were: DAS28-CRP(4v) 3.5?±?1.0 vs. 3.6?±?1.1 (not significant (NS)), DAS28-CRP(3v) 3.4?±?0.9 vs. 3.5?±?0.9 (NS), SDAI 14.2?±?9.4 vs.14.1?±?9.4 (NS) and CDAI 13.4?±?9.3 vs. 13.3?±?9.4 (NS). The LSDs (%LSD) for duplicate assessments of patient-derived scores (visit 2 vs. 1) were: DAS28-CRP(4v) 0.8 (23.2), DAS28-CRP(3v) 0.9 (25.2), SDAI 8.3 (59.9) and CDAI 8.4 (63.8). Similar LSDs were found for differences between duplicate assessments of physician-derived scores and for differences between physician and patient-derived scores. CV_is for SDAI and CDAI were significantly higher than for DAS28-CRP(4v) and DAS28-CRP(3v) (p?<?0.005). Patient- and physician-derived scores agreed closely on group level. On the individual level, the LSDs between patient- and physician-derived scores were considerable but corresponded to both patient and physician intra-observer LSDs. Thus, scores based on patient-performed joint counts may be an alternative to traditional physician-derived scores in patients with stable disease.     

Contribution of subjective Disease Activity Score 28 (DAS28) components to the response to treatment of rheumatoid arthritis

We investigated the contributions made by the subjective components of the Disease Activity Score 28 (DAS28) to the treatment response of rheumatoid arthritis (RA). In addition, factors associated with poor response to treatment at 6 months, despite normalization of objective measures, were examined. A total of 426 newly diagnosed RA patients were included. The DAS28-P score (the subjective components of the DAS28 relative to the total components) was calculated as DAS28-P = 0.56 ? sqrt(TJC28) + 0.014 ? (VAS-GH) /0.56 ? sqrt(TJC28) + 0.28 ? sqrt(SJC28) + 0.7 ? In(erythrocyte sedimentation rate (ESR)) + 0.014 ? (VAS-GH). The European League Against Rheumatism (EULAR) response was assessed after 6 months of treatment. Of those who failed to attain good EULAR responses, those for whom the objective measures (the ESR, the C-reactive protein level, and swollen joints) were normalized were defined as having failed treatment because of subjective measures. The median (IQR) DAS28 score at baseline was 4.8 (4.04–5.49) and that after 6 months of treatment 3.21 (2.41–3.95). The DAS28-P score fell significantly from baseline to 6 months in good (0.43 versus 0.28, p < 0.001) and moderate responders (0.44 versus 0.4, p = 0.003), but not in non-responders (0.43 versus 0.45, p = 0.727). Younger age, a lower DAS28 score, and a lower DAS28-P score at baseline were related to a good EULAR response. Subjects who failed to respond because of subjective measures tended to have higher DAS28-P scores at baseline. We found that RA patients with high DAS28-P scores, reflecting subjective measures, were less likely to achieve good EULAR responses 6 months after treatment initiation and tended not to be classified as good responders despite normalization of objective measures.     

The problem of rheumatoid arthritis disease activity and remission in clinical practice

OBJECTIVE: To investigate the results and feasibility of available scales to measure minimal disease activity (MDA) and remission in rheumatoid arthritis (RA) in the clinic. METHODS: We studied 849 consecutive patients with RA seen in a community rheumatology practice for routine RA care by 4 rheumatologists, beginning in March 2007 and ending in August 2007. Patients and physicians completed a simple form at each visit. We calculated the Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI), physician assessment of global activity, and the Patient Activity Scale (PAS-II). From these we calculated remission and MDA prevalence in this community practice. RESULTS: The DAS28 could not be determined in more than 50% of patients because of referring physician and insurance company restrictions. Remission prevalences differed by assessment method: DAS28 28.5%, CDAI 6.5%-8.1%, physician global 12.5%, PAS 13.7%. MDA was 26.9% using the American College of Rheumatology core set variables, 34.7% using the DAS28, and 26.8% using the PAS-II. The kappa statistic was only fair (0.2 to 0.4) for most comparisons between assessment methods. No significant differences were noted for remission and MDA according to biologic therapy. CONCLUSION: The CDAI and/or physician global and PAS-II are simple acceptable ways to measure RA activity in the clinic, but results differ strikingly according to method. Further standardization appears to be required for full implementation of the CDAI. Caution is urged before using these methods for regulatory purposes.