|Year : 2020 | Volume
| Issue : 4 | Page : 292-297
The effects of educational status and comorbidity on routine assessment of patient index data 3 and its correlation with disease activity score 28 and clinical disease activity index
Kubilay Sahin, Cem Ozisler, Nesibe Karahan Yesil, Fulya Dortbas, Ahmet Omma, Zeynep Ozbalkan Aslar, Yasar Karaaslan
Department of Rheumatology, University of Health Sciences, Ankara Numune Education and Research Hospital, Ankara, Turkey
|Date of Submission||12-Feb-2020|
|Date of Acceptance||29-May-2020|
|Date of Web Publication||18-Dec-2020|
Dr. Kubilay Sahin
Department of Rheumatology, University of Health Sciences, Ankara Numune Education and Research Hospital, Ankara
Source of Support: None, Conflict of Interest: None
Background: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease which leads to significant morbidity. Formal quantitative swollen and tender joint count and indices like disease activity score 28 (DAS28) and clinical disease activity index (CDAI) are very specific for measuring disease activity. Routine assessment of patient index data 3 (RAPID3) is a patient-reported outcome measure used for the assessment and follow-up of RA which can be completed in 10 s. We aimed to determine the effects of patient educational status and comorbidity on RAPID3 and its correlation with DAS28 and CDAI.
Methods: A total of 246 RA patients (80.1% female; mean age: 53.2 years) followed up for 3 years were asked to fill out RAPID3 questionnaires, and DAS28 and CDAI were calculated. Patients were subdivided according to disease severity as Group A (remission-minimal disease activity) and Group B (moderate–severe disease activity). The duration of disease, medications, educational status, comorbidity, and medical history were recorded.
Results: The mean duration of disease was 8.44 years. Of the patients, 27.2% were illiterate and the mean education time was 4.9 years. The 47.6% of the patients had a comorbid disease. The correlation of RAPID3 with DAS28 and CDAI scores was statistically significant (P < 0.001). Similarly, educational status and the presence of comorbidity did not affect this correlation (P < 0.001). The kappa analysis showing compliance of RAPID3 with DAS28 and CDAI scores was also significant (P < 0.001).
Conclusion: RAPID3 is an index which shows a perfect correlation with DAS28/CDAI and can be used routinely for follow-up of RA patients and for decision-making for treatment. It can provide quantitative data with DAS28/CDAI in busy outpatient clinics not only in patients with different educational levels but also in patients with comorbid diseases.
Keywords: Clinical disease activity index, comorbidity, disease activity score, education, routine assessment of patient index data 3, rheumatoid arthritis
|How to cite this article:|
Sahin K, Ozisler C, Yesil NK, Dortbas F, Omma A, Aslar ZO, Karaaslan Y. The effects of educational status and comorbidity on routine assessment of patient index data 3 and its correlation with disease activity score 28 and clinical disease activity index. Indian J Rheumatol 2020;15:292-7
|How to cite this URL:|
Sahin K, Ozisler C, Yesil NK, Dortbas F, Omma A, Aslar ZO, Karaaslan Y. The effects of educational status and comorbidity on routine assessment of patient index data 3 and its correlation with disease activity score 28 and clinical disease activity index. Indian J Rheumatol [serial online] 2020 [cited 2021 Jan 19];15:292-7. Available from: https://www.indianjrheumatol.com/text.asp?2020/15/4/292/290265
| Introduction|| |
Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease which may lead to erosion and deformity in joints and surrounding tissues. It affects approximately 1% of the population and leads to significant morbidity and mortality. In clinical practice, experts agree that rheumatoid inflammation should be promptly and completely controlled and this should be maintained as long as possible. The target of the treatment is to achieve and maintain low disease activity or remission, and the follow-up should include regular assessment of rheumatoid inflammation. This principle is known as strict control in RA treatment. Quantitative measurements are used for the treatment of RA to follow long-term results and to improve the outcome of disease.,, The measurements used in many clinical experiences and research, for example, formal joint count and patient questionnaires, were recently included in routine care to guide clinical decision-making.,, With a strict follow-up, better results were obtained with the disease activity score 28 (DAS28) score compared to nonquantitative RA follow-up. Formal quantitative swollen and tender joint count and indices including these measurements such as DAS28 and clinical disease activity index (CDAI) are very specific for measuring RA activity. However, the most specific measurement is not always the most sensitive for detecting changes. Routine assessment of patient index data 3 (RAPID3) is an index used for the assessment and follow-up of RA patients., It includes measurement of three data points, physical function, pain, and a visual analog scale (VAS) reported by the patient. DAS28-ESR is an index formed by the calculation of 28 swollen joints, 28 tender joints, the erythrocyte sedimentation rate (ESR) or CRP, and a global estimation of the patient using a special formula. In addition, CDAI includes the sum of the swollen joint count, the tender joint count, the global patient estimation, and the global doctor estimation., DAS28 requires 114 s to be completed, and CDAI requires 106 s. RAPID3 was shown to be correlated with DAS28 in clinical studies done with leflunomide, methotrexate, adalimumab, and abatacept, and it was also shown to be as effective as the American College of Rheumatology (ACR) criteria for the discrimination of active and control treatments in clinical tests.,,,,, Some studies have shown that RAPID3 is correlated with DAS28 and CDAI not only for RA activity but also for the assessment of the clinical course.,, Besides, high, moderate, and low disease severity and near-remission (NR) categories based on RAPID3 were compared with high, moderate, and low disease activity and remission categories for DAS28, and CDAI., RAPID3 is a patient-reported outcome measure used for the assessment and follow-up of RA patients which can be completed in <10 s in busy outpatient clinics. However, there are no studies that show the effects of educational status and comorbidity on RAPID3 results. Therefore, we aimed to determine the effects of educational status and comorbid diseases on this assessment and its correlation with DAS28 and CDAI in RA patients.
| Methods|| |
A total of 246 patients with seropositive and/or seronegative RA who met the classification criteria of the ACR and/or the European League Against Rheumatism who were being followed up for at least 3 years at our tertiary rheumatology outpatient clinic were included in the study. Approval was obtained from the local ethics committee, and patients were included cross-sectionally from November 2013 until December 2014. The educational status of the patients was classified as illiterate, elementary school graduate, middle school graduate, high school graduate, and or university graduate. Comorbid diseases included were hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, heart failure, thyroid diseases, pulmonary diseases, amyloidosis, and obesity. Body mass index was classified as normal (18–25 kg/m2), overweight (25.1–29.9 kg/m2), or obesity (>30 kg/m2). The patients were classified as either having or not having comorbidities.
The duration of the disease, the medications, and the duration of intake were recorded. The medical history was obtained, and a physical examination and routine blood tests were carried out. RAPID3, DAS28-ESR, and CDAI were used for the assessment of disease activity. RAPID3 was measured after marking the physical function, pain, and global patient estimation., RAPID3 was calculated by the aid of a medical secretary for illiterate patients and by self-reporting for the other patients. A physical function score was recorded between 0 and 10. The total RAPID3 score is between 0 and 30. The patients were divided into four groups concerning disease severity according to the RAPID3 results. The term “disease severity” was used for the definition of RAPID3 categories because the reported index may also reflect joint injury as disease activity. A patient who scored RAPID3 between 0 and 3 was defined as NR, 3.1–6 as low severity (LS), 6.1–12 as moderate severity (MS), and over 12 as high severity. The patients were also divided into two groups, NR/low disease severity and moderate/high disease severity.
Swollen and tender joint count and patient and doctor VAS were recorded for the DAS28-ESR and CDAI measurements in the patients who were examined by the rheumatology specialist. The ESR measured with the Westergren method was used for DAS28-ESR calculation. Disease activity was calculated with a swollen and tender joint count, and patient VAS and ESR values were calculated using a DAS calculator (dasculator). The patients were divided into four groups according to the disease activity level. The DAS28-ESR value was evaluated as remission if <2.6, as low disease activity if between 2.61 and 3.2, as moderate disease activity if between 3.21 and 5.1, and as high disease activity if >5.1 [Table 1]. The patients were also divided into two groups, remission/low disease activity and moderate/high disease activity.
|Table 1: Disease activity categories for the routine assessment of patient index data 3, disease activity score 28, and clinical disease activity ındex|
Click here to view
The CDAI was calculated with the sum of the swollen and tender joint count, the patient VAS, and the doctor VAS. The patients were divided into four groups concerning disease activity according to the CDAI results. A CDAI value <2.8 was evaluated as remission, a value of 2.9–10 as low disease activity, a value of 10.1–22 as moderate disease activity, and above 22 as high disease activity. The patients were also divided into two groups, remission/low disease activity and moderate/high disease activity.
The Statistical Package for the Social Sciences for Windows (SPSS Statistics 20) was used for the statistical analysis. Distribution of continuous variables was investigated with the Shapiro–Wilk test, and homogeneity of variances was investigated with the Levene test. Descriptive statistics were expressed as mean ± standard deviation or median (minimum–maximum), and categorical variables were expressed as number (n) and percent (%). To compare qualitative data, the one-way ANOVA test was used for intergroup comparison of normally distributed parameters, and the Tukey honestly significant difference was used to detect the group that caused the difference. To assess the percent change ratios, the Kruskal–Wallis test was used for comparison according to the groups, and the Mann–Whitney U-test was used for a post hoc assessment of significant parameters. Variables were investigated with the Shapiro–Wilk test for normality, but normality could not be achieved, and the presence of a statistically significant correlation between continuous variables was investigated with a nonparametric Spearman's correlation analysis and kappa analysis. The results were evaluated with 95% confidence interval and the level of P < 0.05 was statistically significant.
| Results|| |
Of the patients, 197 (80.1%) were female and 49 (19.9%) were male. The age range of the patients was between 19 and 80 years, the mean age being 53.2 ± 12.1 years. Disease activity categories for RAPID3, DAS28, and CDAI are given in [Table 1], and the demographic characteristics and educational status of the patients are summarized in [Table 2].
One hundred and seventeen (47.6%) patients had at least one comorbid disease including hypertension, diabetes mellitus, hypothyroidism, hyperthyroidism, coronary artery disease, pulmonary disease, amyloidosis, and obesity. One hundred and twenty-nine (52.4%) patients did not have any comorbidities. When obesity was evaluated, three (1.2%) patients were thin, 155 (63%) patients were normal weight or overweight, and 88 (35.8%) of the patients were obese.
The median value of ESR (mm/h) was found to be 14 (1–83). The corrected ESR according to age was high in 42 (17.5%) patients and normal in 201 (82.5%) patients, while 21.5% of the patients were seronegative and 78.5% were seropositive.
RAPID3, DAS28, and CDAI were statistically analyzed. The mean value of RAPID3 was found to be 10.24 (0.0–25.7). According to RAPID3, 43 (17.5%) patients were NR, 51 (20.7%) had low disease severity, 55 (22.4%) had moderate disease severity, and 97 (39.4%) had high disease severity. The mean value of DAS28 was found to be 3.15 (0.0–7.61). According to DAS28, 107 (43.5%) patients were in remission, 26 (10.6%) had low disease activity, 75 (30.5%) had moderate disease activity, and 38 (15.4%) had high disease activity. The mean value of CDAI was found to be 9.96 (0.0–52). According to CDAI, 63 (25.6%) patients were in remission, 91 (37%) had low disease activity, 60 (24.4%) had moderate disease activity, and 32 (13%) had high disease activity. The Spearman's correlation coefficient (r2) was 0.67 between RAPID3 and DAS28 in 246 patients (P < 0.001) and r2 was found to be 0.58 between RAPID3 and CDAI (P < 0.001).
Spearman's correlation coefficient (r2) was 0.65 between RAPID3 and DAS28 (P < 0.001) and 0.57 between RAPID3 and CDAI (P < 0.001) for 67 illiterate patients. r2 was 0.75 between RAPID3 and DAS28 (P < 0.001) and 0.82 between RAPID3 and CDAI (P < 0.001) for 179 elementary school, middle, high school, and university graduates.
Spearman's correlation coefficient (r2) was 0.72 between RAPID3 and DAS28 (P < 0.001) and r2 was found to be 0.77 between RAPID3 and CDAI (P < 0.001) for 117 patients who were obese or who had comorbidities. r2 was 0.80 between RAPID3 and DAS28 (P < 0.001) and r2 was found to be 0.81 between RAPID3 and CDAI (P < 0.001) for 129 patients who did not have any comorbid disease or obesity.
All (100%) of the 34 patients who had high disease activity according to DAS28 had moderate or high disease severity according to RAPID3. About 77% of the 107 patients who were in remission according to DAS28 had low disease severity or in NR. The consistency between RAPID3 and DAS28 is summarized in [Table 3]. The kappa coefficient was calculated as 0.63 in the kappa statistics completed to investigate the consistency between RAPID3 and DAS28 (P < 0.001). All (100%) of the 32 patients who had high disease activity according to CDAI had moderate or high disease activity according to RAPID3. Almost 97% of the 63 patients who were in remission according to CDAI had low disease severity or were in remission. The consistency between RAPID3 and CDAI is shown in [Table 4]. The kappa coefficient was calculated as 0.51 in the kappa statistics done to investigate the consistency between RAPID3 and CDAI (P < 0.001).
|Table 3: Investigating the consistency between routine assessment of patient index data 3 and disease activity score 28|
Click here to view
|Table 4: Investigating the consistency between routine assessment of patient index data 3 and clinical disease activity ındex|
Click here to view
| Discussion|| |
Worldwide, follow-up for RA is usually done by taking a medical history and completing a physical examination, and the only quantitative data are laboratory tests. A formal quantitative joint count is not done on most visits; therefore, DAS28 and CDAI, which require a formal joint count, are not applicable for most physician visits of RA patients. A clinician may provide a good follow-up with a physical examination and a medical history. However, the presence of numerical data enables better decision-making by documenting the difference in results and the patient's condition. In our study, RAPID3 scores which can be completed in 10 s were found to be significantly correlated with DAS28 and CDAI, consistent with previous studies.,,, However, different from previous studies, Spearman's correlation coefficient for the illiterate patients was statistically significant (P < 0.001) as well as for patients who had comorbidity and obesity (P < 0.001). In a study conducted with 285 RA patients, Spearman's correlation coefficient was found to be r = 0.66 between RAPID3 and DAS28 and r = 0.74 between RAPID3 and CDAI (P < 0.001), consistent with our results. In another study conducted with 200 RA patients who did not have anemia or comorbid diseases, Spearman's correlation coefficient was found to be r = 0.91 between RAPID3 and DAS28 and r = 0.91 between RAPID3 and CDAI (P < 0.001), similar to the significant correlation detected between RAPID3 and DAS28 and CDAI in our study. In previous studies, the severity categories of RAPID3 were correlated with disease activity categories for DAS28 and CDAI, consistent with our study. Therefore, it can be concluded that RAPID3 is correlated with DAS28 and CDAI for assessment of disease activity in RA,, so it may be used for decision-making for treatment and has value in quantitative RA care. It should be emphasized that no index can take the place of a careful medical history and joint examination for follow-up of RA patients and the test does not eliminate the need for a formal swollen and tender 28 joint count in the follow-up of RA patients. However, RAPID3 can be preferred in the absence of quantitative data except for laboratory tests.,
In the context of the time required, many rheumatologists do not perform a formal quantitative joint count unless it is needed for clinical research or a specific treatment. With RAPID3, spending a lot of extra time is not necessary unless you have an assistant to do the DAS28 and CDAI joint counts. Unfortunately, most rheumatologists do not have an assistant, and their time with each patient is limited. Besides, RAPID3 does not create additional work for the physician because RAPID3 scoring may be taught to a receptionist, nurse, or assistant. In our study, it was completed with the aid of a medical secretary for illiterate patients. This condition does not interfere with patient flow, saves time for the physician, and provides more quantitative data for general rheumatology follow-up. While, according to the reports, a joint count should be done by the same observer at each visit, with RAPID3, the patient may be evaluated quantitatively through a questionnaire at home or another place if the rheumatologist cannot be reached. The fact that it takes a short time makes it attractive for use at busy clinics. Certainly, we do not suggest that RAPID3 will take the place of clinical research or a careful joint examination if there are not any limitations; however, in clinical environments, questionnaires may provide more data than a joint count., The examination provides primary data about the diagnosis and follow-up of RA and clearly reflects disease pathogenesis. A formal joint count is the most specific RA measurement. There are some limitations for the quantitative measurement of swollen and tender joints because its thoroughness and sensitivity are lower than magnetic resonance and ultrasonography.,,,,, RAPID3 is an index that shows an ideal correlation with DAS28 and CDAI that can be used routinely for the follow-up of RA patients for decision-making regarding treatment. Hence, we believe that it can provide quantitative data similar to DAS28 and CDAI regardless of the patients' education level and even when the patients have comorbidities. The prognostic value of physical functions is lower when the loss of labor, treatment costs, and mortality results are evaluated., However, some data suggest that RAPID3 could have a certain value for the follow-up of RA in the presence of a careful joint examination but in the absence of a formal joint count.
| Conclusion|| |
RAPID3 showed perfect correlation and provided quantitative data similar to DAS28 and CDAI. Therefore, it may be used routinely for the follow-up of RA patients and decision-making for treatment, particularly in busy outpatient clinics, not only in patients with different educational levels but also in patients with comorbid diseases.
The present study is author's own work.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
McInnes IB, O' Dell JR. State-of-the-art: Rheumatoid arthritis. Ann Rheum Dis 2010;69:1898-906.
Wolfe F, Cush JJ, O'Dell JR, Kavanaugh A, Kremer JM, Lane NE, et al
. Consensus recommendations for the assessment and treatment of rheumatoid arthritis. J Rheumatol 2001;28:1423-30.
Fransen J, Stucki G, van Riel P. The merits of monitoring: Should we follow all our rheumatoid arthritis patients in daily practice? Rheumatology (Oxford) 2002;41:601-4.
Kiely PD, Brown AK, Edwards CJ, O'Reilly DT, Ostör AJ, Quinn M, et al
. Contemporary treatment principles for early rheumatoid arthritis: A consensus statement. Rheumatology (Oxford) 2009;48:765-72.
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd
, et al
. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheumatism 2010;62:2569-81.
Pincus T, Callahan LF. What is the natural history of rheumatoid arthritis? Rheum Dis Clin North Am 1993;19:123-51.
Wolfe F. The natural history of rheumatoid arthritis. J Rheumatol Suppl 1996;44:13-22.
Pincus T, Segurado OG. Most visits of most patients with rheumatoid arthritis to most rheumatologists do not include a formal quantitative joint count. Ann Rheum Dis 2006;65:820-2.
Wolfe F, Pincus T, Thompson AK, Doyle J. The assessment of rheumatoid arthritis and the acceptability of self-report questionnaires in clinical practice. Arthritis Rheum 2003;49:59-63.
Pincus T, Swearingen CJ, Bergman M, Yazici Y. RAPID3 (Routine Assessment of Patient Index Data 3), a rheumatoid arthritis index without formal joint counts for routine care: Proposed severity categories compared to disease activity score and clinical disease activity index categories. J Rheumatol 2008;35:2136-47.
Pincus T. The DAS is the most specific measure, but a patient questionnaire is the most informative measure to assess rheumatoid arthritis. J Rheumatol 2006;33:834-7.
Pincus T, Swearingen CJ, Bergman MJ, Colglazier CL, Kaell AT, Kunath AM, et al
. 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. Arthritis Care Res (Hoboken) 2010;62:181-9.
Yazici Y, Bergman M, Pincus T. 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. J Rheumatol 2008;35:603-9.
Van Riel PLCM, Fransen J, Welsing PMJ. Evaluation and outcome of the patients with established rheumatoid arthritis. In: Hocberg MC, Silman JS, Weinblatt ME, Weisman MH, editor. Rheumatology. 4th
edition. USA: Mosby Elsevier; 2008:875-85.
Pincus T, Strand V, Koch G, Amara I, Crawford B, Wolfe F, et al
. An index of the three core data set patient questionnaire measures distinguishes efficacy of active treatment from that of placebo as effectively as the American College of Rheumatology 20% response criteria (ACR20) or the Disease Activity Score (DAS) in a rheumatoid arthritis clinical trial. Arthritis Rheum 2003;48:625-30.
Pincus T, Amara I, Koch GG. Continuous indices of core data set measures in rheumatoid arthritis clinical trials: Lower responses to placebo than seen with categorical responses with the American College of Rheumatology 20% criteria. Arthritis Rheum 2005;52:1031-6.
Pincus T, Chung C, Segurado OG, Amara I, Koch GG. An index of patient self-reported outcomes (PRO Index) discriminates effectively between active and control treatment in 4 clinical trials of adalimumab in rheumatoid arthritis. J Rheumatol 2006;33:2146-52.
Pincus T, Bergman MJ, Yazici Y, Hines P, Raghupathi K, Maclean R. An index of only patient-reported outcome measures, routine assessment of patient index data 3 (RAPID3), in two abatacept clinical trials: Similar results to disease activity score (DAS28) and other RAPID indices that include physician-reported measures. Rheumatology (Oxford) 2008;47:345-9.
Wolfe F, Michaud K, Pincus T. A composite disease activity scale for clinical practice, observational studies, and clinical trials: The patient activity scale (PAS/PAS-II). J Rheumatol 2005;32:2410-5.
Singh H, Gupta V, Ray S, Kumar H. Evaluation of disease activity in rheumatoid arthritis by Routine Assessment of Patient Index Data 3 (RAPID3) and its correlation to Disease Activity Score 28 (DAS28) and Clinical Disease Activity Index (CDAI): An Indian experience. Clin Rheumatol 2012;31:1663-9.
Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44-8.
Fransen J, van Riel PL. DAS remission cut points. Clin Exp Rheumatol 2006;24:29-32.
Aletaha D. Pooled indices to measure rheumatoid arthritis activity: A good reflection of the physician's mind? Arthritis Res Ther 2006;8:102-4.
Aletaha D, Smolen JS. Remission of rheumatoid arthritis: Should we care about definitions? Clin Exp Rheumatol 2006;24:45-51.
Pincus T, Swearingen C, Wolfe F. Toward a multidimensional Health Assessment Questionnaire (MDHAQ): Assessment of advanced activities of daily living and psychological status in the patient-friendly health assessment questionnaire format. Arthritis Rheum 1999;42:2220-30.
Pincus T, Sokka T, Kautiainen H. Further development of aphysical function scale on a multidimensional Health Assessment Questionnaire for standard care of patients with rheumatic diseases. J Rheumatol 2005;32:1432-9.
Pincus T, Bergman M, Sokka T, Roth J, Swearingen C, Yazici Y. Visual analog scales in formats other than a 10 centimeterhorizontal line to assess pain and other clinical data. J Rheumatol 2008;35:1550-8.
Kvien TK, Mowinckel P, Heiberg T, Dammann KL, Dale Ø, Aanerud GJ, et al
. Performance of health status measures with a pen based personel digital assistant. Ann Rheum Dis 2005;64:1480-4.
Aletaha D, Smolen J. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): A review of their usefulness and validity in rheumatoid arthritis. Clin Exp Rheumatol 2005;23:S100-8.
Hart LE, Tugwell P, Buchanan WW, Norman GR, Grace EM, Southwell D. Grading of tenderness as a source of interrater error in the Ritchie articular index. J Rheumatol 1985;12:716-7.
Klinkhoff AV, Bellamy N, Bombardier C, Carette S, Chalmers A, Esdaile JM, et al
. An experiment in reducing interobserver variability of the examination for joint tenderness. J Rheumatol 1988;15:492-4.
Tugwell P, Wells G, Strand V, Maetzel A, Bombardier C, Crawford B, et al
. Clinical improvement as reflected in measures of function and health-related quality of life following treatment with leflunomide compared with methotrexate in patients with rheumatoid arthritis: Sensitivity and relative efficiency to detect a treatment effect in a twelve-month, placebo-controlled trial. Arthritis Rheum 2000;43:506-14.
[Table 1], [Table 2], [Table 3], [Table 4]