How to assess early rheumatoid arthritis in daily clinical practice

Rheumatoid arthritis (RA) is a heterogeneous disorder in terms of both clinical presentation and outcome. Our goals in RA are directed towards suppression of signs and symptoms of synovitis, prevention of structural damage, maintenance of functionability and reduction of mortality. IgM rheumatoid factor and anticitrulline antibodies should be recorded in clinical practice since they are prognostic values of outcome. As control of disease activity is pivotal to preventing or at least retarding long-term damage, it is important to define stringent therapeutic aims as well as to follow-up patients in daily practice. The disease activity score 28 is a valuable instrument for this purpose. The assessment of radiographic damage and disability should be assessed regularly. Since increased cardiovascular mortality has been documented even in early RA, other cardiovascular risk factors should be looked for and eventually treated.     

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.     

Monitoring disease activity of rheumatoid arthritis in clinical practice: contributions from clinical trials

Rheumatoid arthritis is a heterogeneous and progressive autoimmune disease, and patients with this condition show varied responses to treatment. Practical, reliable, individually tailored measures of disease activity and treatment responses are needed. Outcome measures used in randomized, controlled trials, including American College of Rheumatology response criteria and Disease Activity Scores, identify when treatment should be initiated or changed, but can be time consuming and impractical in daily practice. Simplified disease activity indices, abbreviated joint counts and patient-report questionnaires are more-convenient ways to assess therapeutic responses in the clinic. Patient-reported measures of physical function, pain and global disease activity best differentiate the results of active treatment from those of placebo treatment in randomized, controlled trials. Improvements in physical function closely reflect changes in health-related quality of life. Recent trials have demonstrated limited correlations between clinical responses and radiographically demonstrated responses; both should be assessed on a regular basis. It is recommended that three domains be assessed in the clinic for therapeutic responses: patient-reported measures of physical function and/or global disease activity; physician assessment of disease activity; and imaging of the hands and/or feet on a biannual basis. Problematic joints and cervical spine involvement should be followed as clinically indicated. Measures of improvement for individually relevant physical activities need to be defined for each patient.     

Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity

Objective

Quantitative assessment of disease activity in rheumatoid arthritis (RA) is important for patient management, and additional objective information may aid rheumatologists in clinical decision making. We validated a recently developed multibiomarker disease activity (MBDA) test relative to clinical disease activity in diverse RA cohorts.

Methods

Serum samples were obtained from the Index for Rheumatoid Arthritis Measurement, Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study, and Leiden Early Arthritis Clinic cohorts. Levels of 12 biomarkers were measured and combined according to a prespecified algorithm to generate the composite MBDA score. The relationship of the MBDA score to clinical disease activity was characterized separately in seropositive and seronegative patients using Pearson's correlations and the area under the receiver operating characteristic curve (AUROC) to discriminate between patients with low and moderate/high disease activity. Associations between changes in MBDA score and clinical responses 6–12 weeks after initiation of anti–tumor necrosis factor or methotrexate treatment were evaluated by the AUROC.

Results

The MBDA score was significantly associated with the Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP) in both seropositive (AUROC 0.77, P < 0.001) and seronegative (AUROC 0.70, P < 0.001) patients. In subgroups based on age, sex, body mass index, and treatment, the MBDA score was associated with the DAS28‐CRP (P < 0.05) in all seropositive and most seronegative subgroups. Changes in the MBDA score at 6–12 weeks could discriminate both American College of Rheumatology criteria for 50% improvement responses (P = 0.03) and DAS28‐CRP improvement (P = 0.002). Changes in the MBDA score at 2 weeks were also associated with subsequent DAS28‐CRP response (P = 0.02).

Conclusion

Our findings establish the criterion and discriminant validity of a novel multibiomarker test as an objective measure of RA disease activity to aid in the management of RA in patients with this condition.     

A simplified disease activity index for rheumatoid arthritis for use in clinical practice

Objective. The objective of this study was to verify the usefulnessof a simple disease activity index (SDAI) for rheumatoid arthritis(RA). Methods. The SDAI is the numerical sum of five outcome parameters: tenderand swollen joint count (based on a 28-joint assessment), patientand physician global assessment of disease activity [visualanalogue scale (VAS) 0–10 cm] and level of C-reactiveprotein (mg/dl, normal <1 mg/dl). Analysis initially focusedon MN301, one of the three phase III clinical trials of leflunomide,in order to assess possible correlations between the SDAI andthe Health Assessment Questionnaire (HAQ) and Disease ActivityScore 28 (DAS 28). Results were then compared with the othertwo trials, MN302 and US301. A total of 1839 patients were evaluated.At baseline, 6 and 12 months, the SDAI, DAS 28, American Collegeof Rheumatology (ACR) response criteria and mean HAQ scoreswere determined for each patient and compared by linear regressionfor significant correlation. The SDAI was compared qualitativelyto the ACR 20% at 3, 6 and 12 months. The index was furthervalidated by comparing the SDAI with survey results obtainedfrom rheumatologists' evaluations of disease activity in testcases. The survey results included defining categorical changesin the SDAI indicating major, minor or no improvement in diseaseactivity in response to treatment. Changes in total Sharp scoreat 6 and 12 months of treatment were determined for each ofthese categories of the SDAI and for comparable categories ofthe DAS 28. Results. The mean SDAI calculated for patients at baseline instudy MN301 was 50.06 (range 25.10–96.10) and was, respectively,50.55 (range 22.10–98.10) and 43.20 (range 12.90–78.20)in studies MN302 and US301. In all three trials, the SDAI wascorrelated with a high level of statistical significance tothe DAS 28 and HAQ scores at baseline, endpoint and change atendpoint. Patients achieving the ACR 20, 50, 70 or 90% responseshowed proportionate changes in the SDAI. Analysis of surveyedphysician responses showed a significant association betweenthe perception of disease activity and the SDAI, as well aschanges in the SDAI. Qualitative analysis of radiographic progressionat 6 and 12 months for patients showing either major, minoror no improvement of the SDAI showed correspondingly largerincreases of the total Sharp score at 12 months. Conclusion. The SDAI is a valid and sensitive assessment ofdisease activity and treatment response that is comparable withthe DAS 28 and ACR response criteria; it is easy to calculateand therefore a viable tool for day-to-day clinical assessmentof RA treatment. Overall results indicate that the SDAI hascontent, criterion and construct validity. KEY WORDS: Simple disease activity index, Rheumatoid arthritis, Clinical practice. Correspondence to: J. S. Smolen, Department of Rheumatology,Internal Medicine III, Vienna General Hospital, University ofVienna, Waehringer Guertel 18–20, A-1090 Vienna, Austria.E-mail: josef.smolen{at}wienkav.at     

Standard treatment in daily clinical practice for early rheumatoid arthritis improved disease activity from 2001 to 2006

We aimed to clarify the degree of improvement in disease control following early treatment of rheumatoid arthritis (RA) in daily clinical practice in 2006 compared to that in 2001. Using a large observational Japanese RA cohort (IORRA), we analyzed changes in clinical parameters, including disease activity assessed by the disease activity score 28 (DAS28) and physical disability assessed by the Japanese version of the Health Assessment Questionnaire (J-HAQ), which occurred within 2 years of cohort inception. All patients had enrolled in the IORRA cohort within 1 year of RA onset, in either 2001 (2001-cohort) or 2006 (2006-cohort). For both cohorts, changes in clinical features over 2 years were compared by Fisher’s exact test or the Wilcoxon test. The 2001-cohort included 71 patients and the 2006-cohort included 56 patients. Over the 2-year period for each cohort, DAS28 significantly decreased from 3.9 to 3.5 in the 2001-cohort (p < 0.001) and from 4.1 to 3.1 in the 2006-cohort (p < 0.0001), and J-HAQ significantly decreased from 0.62 to 0.49 (p < 0.02) in the 2001-cohort and from 0.71 to 0.41 (p < 0.001) in the 2006-cohort. Greater improvement in disease activity over 2 years occurred in the 2006-cohort than in the 2001-cohort (p < 0.05). Better disease control was obtained following changes in RA treatment strategy that occurred in Japan between 2001 and 2006.     

Standard treatment in daily clinical practice for early rheumatoid arthritis improved disease activity from 2001 to 2006

Abstract

We aimed to clarify the degree of improvement in disease control following early treatment of rheumatoid arthritis (RA) in daily clinical practice in 2006 compared to that in 2001. Using a large observational Japanese RA cohort (IORRA), we analyzed changes in clinical parameters, including disease activity assessed by the disease activity score 28 (DAS28) and physical disability assessed by the Japanese version of the Health Assessment Questionnaire (J-HAQ), which occurred within 2 years of cohort inception. All patients had enrolled in the IORRA cohort within 1 year of RA onset, in either 2001 (2001-cohort) or 2006 (2006-cohort). For both cohorts, changes in clinical features over 2 years were compared by Fisher’s exact test or the Wilcoxon test. The 2001-cohort included 71 patients and the 2006-cohort included 56 patients. Over the 2-year period for each cohort, DAS28 significantly decreased from 3.9 to 3.5 in the 2001-cohort (p < 0.001) and from 4.1 to 3.1 in the 2006-cohort (p < 0.0001), and J-HAQ significantly decreased from 0.62 to 0.49 (p < 0.02) in the 2001-cohort and from 0.71 to 0.41 (p < 0.001) in the 2006-cohort. Greater improvement in disease activity over 2 years occurred in the 2006-cohort than in the 2001-cohort (p < 0.05). Better disease control was obtained following changes in RA treatment strategy that occurred in Japan between 2001 and 2006.     

Quantitative measures and indices to assess rheumatoid arthritis in clinical trials and clinical care

Modern medical care has been advanced, in large part, by quantitative measures that provide single, easily-assessed end points for clinical trials, clinical research, or clinical care (eg, blood pressure, serum cholesterol). In rheumatoid arthritis, several types of quantitative measures are used to assess patient status, including formal joint counts; radiographic scores; laboratory tests; patient self-report questionnaire measures of physical function, pain, global status, morning stiffness, and fatigue; as well as physical measures of functional status. Each of these measures is effective to document changes of status with treatment in groups of patients; however, no single measure can serve as a "gold standard" to document changes in each individual patient. Therefore, the measures have been combined into pooled indices that can be applied to individual patients in clinical research and clinical care.     

Patients' own ability to assess activity of their rheumatoid arthritis

SIR, Increasingly patients are able to access their RheumatologyDepartment via nurse-led Rheumatology helplines and, due tothe over-booking of our clinics and the long distances patientshave to travel to attend, there clearly is a potential for departmentsto develop a telephone follow-up service for patients with rheumatoidarthritis (RA). Published work on Rheumatology telephone followup concentrates on a doctor- rather than nurse-led service [1     

A clinical and biochemical assessment of methotrexate in rheumatoid arthritis

Summary Low-dose methotrexate has gained widespread acceptance as a second-line agent in rheumatoid arthritis (RA). The Leeds Human Model Screening System (LHMSS) is a validated screening mechanism allowing the rapid evaluation of compounds for their potential as anti-rheumatic agents, the results of which have been confirmed in longer term studies. We have evaluated methotrexate in patients with RA using the LHMSS at a maintenance dose of 10mg/week. Significant change occurred in four out of eleven variables over a 24-week period (p<0.01). This degree of change is greater than that seen with nonsteroidal anti-inflammatory agents but less than with other recognised second-line agents such as D-penicillamine, suggesting that methotrexate may have less potential as a second-line agent than D-penicillamine.     

Physician ability to assess rheumatoid arthritis disease activity using an electronic medical record–based disease activity calculator

Objective

To assess physicians' concordance with Disease Activity Score in 28 joints (DAS28) categories calculated by an electronic medical record (EMR)–embedded disease activity calculator, as well as attitudes toward this application.

Methods

Fifteen rheumatologists used the EMR‐embedded disease activity calculator to predict a rheumatoid arthritis (RA) DAS28 disease activity category at the time of each clinical encounter.

Results

Physician‐predicted DAS28 disease activity categories ranged from high (>5.1, 15% of cohort, 66 of 429 patient visits) to moderate (>3.2–5.1, 21% of cohort, 90 of 429 patient visits) to low (2.6–3.2, 29% of cohort, 123 of 429 patient visits) to remission (<2.6, 35% of cohort, 150 of 429 patient visits). Overall concordance between calculated DAS28 results and physician‐predicted RA disease activity was 64%. Using either the physician‐predicted or the calculated DAS28 category as the gold standard, accuracy was greatest for patients in remission (75% and 88% accuracy, respectively) and those with high disease activity (68% and 79% accuracy, respectively), and less for patients with moderate (48% and 62% accuracy, respectively) or low disease activity (62% and 31% accuracy, respectively).

Conclusion

Accurate physician prediction of DAS28 remission and high disease activity categories, even without immediate availability of the erythrocyte sedimentation rate or the C‐reactive protein level at the time of the visit, may be used to guide quantitatively driven outpatient RA management. This article was published online on March 30, 2009. An error was subsequently identified in Figure 4. This notice is included in the online and print versions to indicate that both have been corrected.     

Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score.

An investigation of clinical and laboratory variables which might form the basis for judging disease activity in clinical practice was made by six rheumatologists in a prospective study of up to three years' duration of 113 patients with early rheumatoid arthritis. Decisions to start treatment with slow acting antirheumatic drugs were equated with moments of high disease activity. If treatment with slow acting antirheumatic drugs was not started or if the slow acting antirheumatic drug remained unchanged for at least one year or if treatment was stopped because of disease remission, this was equated with periods of low disease activity. Two groups, one with high and one with low disease activity according to the above criteria, were formed. Factor analysis was performed to enable easy handling of the large number of clinical and laboratory variables without loss of information; this resulted in five factors. Next, discriminant analysis was done to determine to what extent each factor contributed to discrimination between the two groups of differing disease activity. Finally, a multiple regression analysis was carried out to determine which laboratory and clinical variables underlie the factors of the discriminant function, resulting in a 'disease activity score'. This score consisted of the following variables: Ritchie index, swollen joints, erythrocyte sedimentation rate, and general health, in declining importance. The rheumatologists' decisions to prescribe slow acting antirheumatic drugs, or not, were mainly based on articular symptoms.