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Publications and source records attributed to Harold E Paulus.
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OBJECTIVE: Structural validity for the Health Assessment Questionnaire-Disability Index (HAQ-DI) has recently been provided for patients with rheumatoid arthritis (RA). The goal of the current study was to examine the structural validity of the HAQ-DI in patients with systemic sclerosis (SSc, scleroderma) and to compare its performance with that in patients with RA. METHODS: The HAQ-DI structural validity was first assessed in a sample of 100 scleroderma patients using confirmatory factor analysis. Second, the similarity of factor structures between SSc patients (n = 291) and RA patients (n = 278) was tested using a multigroup structural validity model to assure that comparison of scores between these two diagnostic groups is appropriate. RESULTS: Results yielded a single-factor HAQ-DI score which favored the current scoring system of the HAQ-DI (model fit was CFI = 0.99 and RMSEA = 0.04). Moreover, even the most stringent model of multigroup structural validity affirmed the similarity between SSc and RA patients on the HAQ-DI (model fit was CFI = 0.99 and RMSEA = 0.04) nor was it different from a model without any demands on group similarity: CFI difference = 0.007; chi(2) = 4.29, df = 26, p=0.99. CONCLUSION: The current results indicate that a single-factor HAQ-DI is appropriate for future clinical trials in scleroderma and, in addition, HAQ-DI scores among patients with SSc and early RA can be compared legitimately with one another.
OBJECTIVE: To determine whether the tumor necrosis factor alpha (TNFA) -308 guanine-to-adenosine polymorphism and/or the shared epitope (SE) is associated with radiographic damage in patients with early rheumatoid arthritis (RA). METHODS: The cohort consisted of 189 patients with early seropositive RA (median 5.6 months since symptom onset) who had active disease, no previous disease-modifying antirheumatic drug treatment, and >or=2 sets of scored radiographs of the hands/wrists and forefeet. TNFA -308 polymorphism was analyzed by polymerase chain reaction pyrosequencing. The SE was defined as presence of any 1 of the following HLA-DRB1 alleles: *0101, *0102, *0401, *0404, *0405, *0408, *0410, *1001, *1402, or *1406. Radiographic progression was assessed by the total Sharp score. RESULTS: Using a weighted least-squares regression analysis, patients with the -308 TNFA AA plus AG genotypes (n=49) had significantly higher rates of progression in erosion scores (median 0.84 versus 0.48 units/year), joint space narrowing (JSN) scores (0.42 versus 0.04), and total Sharp scores (1.70 versus 0.61) compared with patients with the TNFA GG genotype (n=140). Presence of the SE (n=137) was associated with significantly lower progression rates (per year) for total Sharp scores (median 0.9 versus 1.25 units/year) and JSN scores (0.04 versus 0.41), but not for erosion scores (0.50 versus 0.61) compared with patients without the SE (n=52). In a least-squares multiple linear regression model, the presence of the AA plus AG genotypes was associated with a significantly higher progression rate after adjusting for the presence of the SE, interaction between the SE and the AA plus AG genotypes, baseline log C-reactive protein level, Health Assessment Questionnaire Disability Index, total Sharp score, swollen joint count, and presence of osteophytes (osteoarthritis). There was a strong linkage disequilibrium between DRB1*0301 and TNFA polymorphism (D'=0.84, r2=0.45, P<0.001). CONCLUSION: This study showed an association between the TNFA -308 polymorphism and progression of radiographic damage in patients with early seropositive RA. This association appeared to be independent of the SE, but might be dependent on other genetic variants in linkage disequilibrium with the -308 TNFA A allele and DRB1*0301. Further studies should be conducted to validate these results in both longitudinal observational cohorts and randomized clinical trials.
OBJECTIVE: To evaluate the effectiveness of select biologics, methotrexate (MTX), and other disease-modifying anti-rheumatic drugs (DMARDs) in the management of adult rheumatoid arthritis (RA) in routine clinical practice. RESEARCH DESIGN AND METHODS: RADIUS (Rheumatoid Arthritis DMARD Intervention and Utilization Study) comprises two prospective, 5-year, observational registries of over 10 000 patients. Over 4600 patients who initiated MTX or a biologic regimen (etanercept [ETN], infliximab [INF], ETN + MTX, and INF + MTX) and who had at least one on-regimen, follow-up evaluation, were included in this analysis. Adalimumab was not included because it had not yet received FDA approval at RADIUS initiation. Other common DMARD regimens (N = 762) were also compared with MTX. Patients who initiated less commonly used regimens, such as anakinra or cyclosporine, and those who did not have at least one on-regimen, follow-up evaluation, were not eligible for this analysis. Because ESR/CRP measurements were often not available, a modified ACR20 response (mACR20), defined as three out of four response criteria excluding ESR/CRP, was used to assess response at 12 months. Logistic regression analysis was performed to control for baseline covariates that may affect outcomes. MAIN OUTCOME MEASURES: The primary endpoint was the proportion of patients who achieved a mACR20 response at 12 months post-RADIUS entry. RESULTS: After adjusting for baseline covariates, patients receiving either ETN + MTX or ETN monotherapy were more likely to achieve a mACR20 response at 12 months than patients receiving MTX alone (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.09-1.52; p < 0.01 and OR 1.23, 95% CI 1.02-1.47; p < 0.05, respectively). Conversely, patients treated with MTX + leflunomide (LEF) were less likely to achieve a mACR20 response than those receiving MTX alone (OR 0.68, 95% CI 0.48-0.96; p < 0.05). Significant differences were not observed between patients receiving MTX alone and either INF + MTX, MTX + hydroxychloroquine, MTX + hydroxychloroquine + sulfasalazine, INF monotherapy, or LEF monotherapy. CONCLUSION: These data from routine rheumatology clinical practice settings highlight the effectiveness of common biologic and DMARD therapies, and provide additional data beyond those of randomized, controlled trials.
OBJECTIVE: Rheumatoid Arthritis (RA) Disease-Modifying Anti-Rheumatic Drug (DMARD) Intervention and Utilization Study (RADIUS) is a unique, real-world, prospective, 5-year, observational study of over 10 000 patients with RA. RADIUS provides a snapshot of use patterns, effectiveness, and safety of DMARDs, biologics, and combination therapies used to manage RA in clinical practice. RESEARCH DESIGN AND METHODS: Patients with RA requiring a new DMARD or biologic (addition or switch) were eligible for the RADIUS study. Two separate patient cohorts were enrolled; RADIUS 1 patients initiated any new therapy at entry, and RADIUS 2 patients initiated etanercept at entry. Patient demographics and disease activity measures were collected at study entry, and baseline characteristics were summarized for various subgroups. Effectiveness, safety, and patterns of use will be tracked for therapies utilized during the 5-year study. RESULTS: RADIUS 1 enrolled 4959 patients, and RADIUS 2 enrolled 5102 patients, mostly at community private practices (88%). In RADIUS 1, most patients initiated methotrexate (MTX) monotherapy, followed by MTX in combination with a biologic (e.g. infliximab plus MTX) or other DMARD. In RADIUS 2, most patients initiated etanercept in combination with MTX, followed by etanercept monotherapy. When a new therapy was required, physicians tended to add another therapy versus switching therapies. Patients initiating a biologic had a longer duration of RA and more severe disease compared with patients initiating non-biologic therapy. CONCLUSIONS: These real-world data provide evidence of the prescribing practices of rheumatologists in 2001-2003. Future analyses will allow evidence-based comparisons of the long-term safety and effectiveness of DMARDs, biologics, and combination therapies to assist physicians in clinical decision-making.
OBJECTIVE: To assess the psychometric characteristics of the original 33-item Cedars-Sinai Health-Related Quality of Life in Rheumatoid Arthritis Questionnaire (O-CSHQ-RA) and 11-item CSHQ-RA Short Form (SF) using a representative population of patients with rheumatoid arthritis (RA) from 55 sites across the United States. METHODS: Data were from a 24-week multicenter, open-label, single-arm study of 312 RA patients receiving anakinra. Cronbach's alpha coefficient was used to indicate the internal consistency. Test-retest reliability was assessed by establishing the intraclass correlation coefficient (ICC) for screening and baseline visit responses. Convergent validity was tested with the Pearson correlation coefficient. Analysis of variance was performed to determine discriminant validity. A Wilcoxon signed-rank test and analysis of covariance were used to assess the responsiveness. A discriminant function was generated to determine the clinically meaningful change. RESULTS: Test-retest reliability was demonstrated for both versions of the CSHQ-RA, with ICC ranging from 0.82 to 0.94. Cronbach's alpha coefficients were > or = 0.9, indicating good internal consistency. Pearson correlations between health-related quality of life instruments and CSHQ-RA measures ranged from -0.33 to -0.73 and 0.39 to 0.76, demonstrating good convergent validity. Scores on both versions of the CSHQ-RA differed significantly (p < 0.0001) for patients with different levels of physical disability as measured by the Stanford Health Assessment Questionnaire. Both instruments were responsive to differences in patient health as measured by the general health question (p < 0.0001). Clinically meaningful changes were calculated for all 5 domains of the O-CSHQ-RA (6.9-14.0) and the overall O-CSHQ-RA SF (12.7). CONCLUSION: These results support the validity and reliability of both the original CSHQ-RA and the 11-item CSHQ-RA SF when tested in a representative patient population.
OBJECTIVE: Biological agents have revolutionized the treatment of rheumatoid arthritis (RA). Given the previously documented ethnic disparity in the health service literature, we sought to determine if ethnic difference exists in the lag time between the diagnosis of RA and use of first biological agent. METHODS: RADIUS 1 and 2 are observational studies designed to document how rheumatologists treat RA across the United States. The sample analyzed here included early patients with RA who entered RADIUS with the initiation of the first biological agent. Ethnic status was categorized as White (W), African American (AA), and Hispanic (H). Lag time (months from RA diagnosis to initiation of the first biological agent) was the principal outcome variable. RESULTS: Compared to W (n=1616), AA (n=147) and H (n=116) were more likely to be female, younger, and have less than a high school education. Despite similar swollen and tender joint counts, AA and H had more active disease on the basis of Health Assessment Questionnaire and patient global assessments. Almost 97% of patients had some type of insurance coverage. On multivariable analysis, ethnic affiliation was not associated with lag time (14.5 months W vs 14.9 AA vs 14.3 H; p=NS). Similarly, there were also no significant ethnic differences in time to first DMARD (e.g., methotrexate) initiation. CONCLUSION: In a national sample of patients with RA, most of whom were insured, the length of time from diagnosis of RA to initiation of the first biological agent was not significantly different among Whites, African Americans, and Hispanics.
OBJECTIVE: The extensively used Health Assessment Questionnaire Disability Index (HAQ-DI) has been well received by the research and clinical community, notably because of its measurement strengths including reliability and stability of scores over time, utility in observational studies and clinical trials, predictive relationship with morbidity and mortality in rheumatoid arthritis (RA), and its translation for use in different countries. However, HAQ-DI scoring has not been validated. The purpose of this study was to examine the structural validity of the HAQ-DI and evaluate the latent factors underlying HAQ-DI scoring. METHODS: This study used a cross-validation approach on a total of 278 patients with RA. Exploratory and confirmatory factor analyses were performed. RESULTS: Results yielded a single-factor HAQ-DI score, which favored the current scoring system of the HAQ-DI. Additionally, modification indices suggested improved model fit with the secondary inclusion of correlated residual scores from a motor skills subdomain. CONCLUSION: The current study provides the first validation of the HAQ-DI scoring system as determined by its latent factor structure. In addition, the findings suggest some benefit from a secondary interpretation of the scores based on domains that measure motor skills.
OBJECTIVE: To investigate the impact of patient age at symptom onset on radiographic joint damage at study entry, and on subsequent progression of damage in a cohort of patients with early seropositive rheumatoid arthritis (RA). METHODS: We studied 186 patients with RA of <15 months' duration. All patients had active disease and had not received disease-modifying antirheumatic drugs. At study entry and during followup, total Sharp scores (TSS), RA-associated joint space narrowing (RA-JSN), and erosions were determined on hand and foot radiographs. Baseline radiographs were also scored for osteoarthritis (OA)-related JSN (OA-JSN) and osteophytes. Older patients (>55 years) and younger patients (</=55 years) were compared by t-test, Mann-Whitney U test, chi-square, or Fisher's exact test. Multiple linear regression models were also constructed. RESULTS: The older group (n = 74) had a higher baseline total Sharp score (median 6.21) compared with the younger group (n = 112) (median 2.33) (P = 0.0002). This was mainly due to a higher baseline JSN score in the older group (median 3.96 versus 1.08) and not to differences in erosion score (median 0.91 versus 0.70). Disease activity and duration of RA symptoms were similar in the 2 groups, as were progression rates of the TSS, JSN score, and erosion score. At baseline, 26% of patients had osteophytes, with a prevalence of 13% in the younger age group and 50% in the older group. The presence of OA-JSN was highly correlated with the presence of osteophytes (r = 0.72). Also, increased age and RA-JSN were associated with increased severity of osteophytes and OA-JSN at baseline. Multiple linear regression analysis showed that both age and hand osteophytes contributed to the increase in baseline RA-JSN score and TSS, but not to erosion score. CONCLUSION: In a cohort of patients with early RA, an increase in the baseline RA-JSN score and TSS can be accounted for in part by the presence of hand OA.
OBJECTIVE: To examine the effect of folic acid on the efficacy of methotrexate (MTX) treatment in rheumatoid arthritis (RA) at 12 months in 2 phase III randomized controlled trials (RCTs) of leflunomide in which MTX was used as a comparator. METHODS: Analyses were restricted to patients randomized to receive MTX who had rheumatoid factor data. The US study recruited 482 patients with active RA; 179 received at least 1 dose of MTX, and all were mandated to receive 1 mg of oral folic acid once or twice daily. The multinational European study recruited 999 patients with active RA; 489 received at least 1 dose of MTX, and oral folic acid was not required, although 50 received folate after developing an adverse event. Because of similar entry criteria for both studies, the data for patients with available primary outcome data at week 52 were pooled (n = 668), and the patients were grouped by folic acid use (n = 225) and nonuse (n = 443). To account for the significant between-study differences in the MTX groups, baseline covariates were adjusted using propensity scores so that folic acid users could be matched with nonusers. This allowed for a comparison of differences in American College of Rheumatology (ACR) 20% improvement criteria at week 52. RESULTS: At study entry, non-folic acid users had a significantly lower mean body weight, shorter mean RA duration, and higher mean disease activity (measured by joint counts, patient's and physician's global assessments, and acute-phase reactant levels). The mean MTX dosage at week 52 was similar in the 2 RCTs. Using propensity score matching techniques, the proportion of patients achieving an ACR 20% response at week 52 averaged 17% higher in the non-folic acid group than in the folic acid group (range 15-21%). Similarly, the proportion of patients achieving ACR 50% and ACR 70% responses averaged 14% (range 12-16%) and 12% (range 9-14%) higher, respectively, in the non-folic acid group. Adverse events were reported in 93% of US study patients and 94% of the multinational study patients. Elevated liver transaminase levels (above the upper limit of normal) were reported in 29% of the US study patients (majority receiving folic acid) and 62% of the multinational study patients (majority not receiving folic acid). CONCLUSION: After using propensity scores to adjust for differences in the baseline characteristics of folic acid users and non-folic acid users, 9-21% fewer MTX-treated RA patients taking folic acid had ACR 20%, 50%, or 70% improvement at 52 weeks compared with those who did not receive folic acid in the 2 phase III RA clinical trials. As a post hoc analysis, the results of this data analysis should be considered "hypothesis generating" and an impetus for future studies regarding the effects of folic acid on the efficacy of MTX in RA.
OBJECTIVE: To evaluate the effect of age adjustment on baseline erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in patients with late-onset rheumatoid arthritis (LORA, age > or = 55 yrs) and younger-onset RA (YORA, age < 55 yrs) in a cohort with early, rheumatoid factor (RF) positive RA that has not received disease modifying antirheumatic drugs (DMARD). METHODS: In an ongoing prospective cohort study of 263 patients with seropositive RA who were enrolled within 14 months of symptom onset, baseline assessments included ESR, CRP, tender and swollen joint counts, and functional status. Westergren ESR determinations were performed in the rheumatologist's office or in a local laboratory using appropriate methods. CRP were performed at the Specialty Laboratories in Santa Monica, CA, using Behring nephelometry. Percentages of patients with greater than the upper limit of normal (ULN) laboratory values using both age-unadjusted and age-adjusted ESR and CRP values were determined. The late-onset and younger-onset RA patients were compared using Wilcoxon rank-sum and chi-square tests. RESULTS: At study entry, both the YORA and LORA patients had comparable symptom duration, disease activity scores, tender and swollen joint counts, and Health Assessment Questionnaire values. RF, CRP, and ESR were significantly higher (p < 0.05) in LORA patients. Although the percentages of patients with age-unadjusted ESR and CRP above ULN were higher in LORA patients, the percentages exceeding the age-adjusted ULN did not differ significantly between the YORA and LORA groups. CONCLUSION: In patients with late-onset and younger-onset RA with similar disease duration and severity, the apparent discrepancy in elevation of both the baseline ESR and CRP disappears after age-adjustment.
OBJECTIVE: To develop an abridged version of the 33-item Cedars-Sinai Health-Related Quality of Life in Rheumatoid Arthritis instrument (CSHQ-RA) and test the validity and reliability of the abridged instrument. METHODS: Items from the original 33-item, 5-domain CSHQ-RA were assessed using psychometric and regression analyses of survey responses from 274 patients with rheumatoid arthritis. Items were retained in the final instrument based on statistical analysis and evaluation by an expert panel. Test-retest reliability, internal consistency, convergent and discriminant validity, and ceiling and floor effects were examined for the shortened CSHQ-RA. RESULTS: Statistical analysis and expert assessment yielded an 11-item instrument including questions in 4 domains. Test-retest reliability and internal consistency were high and the instrument showed good convergent and discriminant validity. CONCLUSION: The abridged CSHQ-RA short form is a valid and reliable instrument that can be used to examine the impact of RA on patients' health-related quality of life. Prospective validation in clinical trial settings is warranted.
OBJECTIVE: To categorize radiographic joint damage as progressive or nonprogressive in individuals with rheumatoid arthritis (RA) participating in clinical studies. METHODS: Using the total Sharp radiographic damage score, erosion score, and joint space narrowing (JSN) score for 751 serial films of the hand/wrist and forefoot obtained from 190 patients with early RA during 6-60 months of followup (mean 31 months), various threshold values for progression of joint damage were evaluated singly and in various combinations. For each patient, the progression rate was estimated from the linear regression line for all available radiographic time points. After preliminary screening, 23 candidate definitions were tested to select a definition that discriminated well between radiographic progression and radiographic nonprogression. RESULTS: The definition selected describes radiographic nonprogression in individual patients as an increase of < or =0.1 in the standardized response mean of the trimmed population (the central 95% of patients) for > or =5 of 6 change measures (erosion scores and JSN scores for the fingers, wrists, and feet). Using this definition, 59% of the 190 patients with early RA were defined as having nonprogressive radiographic damage. Moreover, 95% of 95 patients with progression of the total Sharp score at or below the median and 24% of 95 patients with progression of the total Sharp score above the median were defined as having nonprogressive joint damage (chi(2) = 98, P < 0.0001), as were 97% of patients in the lowest quintile of total Sharp score progression rates and none of the patients in the highest progression quintile. Patients defined as nonprogressors had significantly lower baseline levels of C-reactive protein and lower erythrocyte sedimentation rates compared with patients defined as progressors, and those patients in the nonprogressive joint damage group more frequently had American College of Rheumatology 20% and 50% improvement criteria responses, "good" improvements (decrease of > or =1.2) in the Disease Activity Score, and > or =50% decreases in the swollen joint counts during the first 2 years of followup. CONCLUSION: RA joint damage in an observational cohort can be classified as progressive or nonprogressive with the use of a composite definition. Validation and/or refinement of this definition is needed by utilizing the data from controlled clinical trials that compare placebo with active treatment.
OBJECTIVE: To determine whether the RANKL and HLA-DRB1 "shared epitope" (SE) genotypes contribute to the development of rheumatoid arthritis (RA). METHODS: We studied 237 patients with early RA (within 15 months of symptom onset) who were seropositive for rheumatoid factor. HLA-DRB1 genotyping was performed using the polymerase chain reaction (PCR)-based oligonucleotide probe assay. RANKL polymorphisms were analyzed using PCR pyrosequencing for SNP1 and fluorescence-based PCR for the presence or absence of the TAAA insertion. RESULTS: The presence of SE-containing DRB1*04 alleles was associated with an earlier age at RA onset (mean +/- SD 47 +/- 12.7 years versus 53 +/- 12.5 years in SE- patients; P = 0.0004). The 2 novel RANKL polymorphisms were in strong linkage disequilibrium (P < 0.0001) and were associated with earlier ages at disease onset (e.g., for the CC versus CT/TT genotypes, 44 +/- 13.5 years versus 51 +/- 12.7 years; P = 0.0080). The mean age at disease onset in SE+ patients with the RANKL-CC genotype (35 +/- 7.2 years) was a mean of 18 years younger than in SE- patients with RANKL-CT/TT (53 +/- 12.5 years; P < 0.0001) and was 17 years younger than in SE- patients with RANKL-CC (52 +/- 13.2 years; P = 0.0005). The proportion of patients with both the SE and RANKL risk alleles was highest (23%) in those who developed RA during their third decade of life (ages 20-30 years), with a declining trend among those who developed RA during their fourth (16%), fifth (5%), and sixth or later (0%) decades. Interestingly, 92% of the patients diagnosed as having RA between ages 20 and 30 years carried at least 1 of the RA-associated DRB1*04 alleles, suggesting a strong influence of the SE in the early onset of RA. The majority of patients who developed RA symptoms in their third to fifth decades (74 of 119 [62%]) carried at least 1 copy of the DRB1*04 alleles; in contrast, fewer than half of the patients who developed RA in their sixth decade or later (50 of 118 [42%]) had DRB1*04 alleles. RANKL genotypes were not associated with erosive disease at baseline or with the yearly progression rate of radiographic joint damage. CONCLUSION: This study provides the first evidence that novel RANKL polymorphisms were associated with an earlier age at RA onset in SE+, but not SE-, patients and that an interaction between SE-containing HLA-DRB1 and RANKL polymorphisms increased the disease penetrance, resulting in a mean age at RA onset that was 18-20 years younger. Our results also suggested genetic differences between patients with early-onset and those with late-onset RA.
OBJECTIVE: To evaluate the interrater reliability of rheumatologist diagnosis of rheumatoid arthritis (RA) and the concordance between rheumatologist and computer algorithms for assessing the accuracy of a diagnosis of RA. METHODS: Self-reported data regarding symptoms and signs for a diagnosis of RA were considered by a panel of rheumatologists and by computer algorithms to assess the probability of a diagnosis of RA for 90 patients. The rheumatologists' review was validated through medical record. RESULTS: The interrater reliability among rheumatologists regarding a diagnosis of RA was 84%; the chance-corrected agreement (kappa) was 0.66. Agreement between the rheumatologists' rating and the best-performing algorithm was 95%. Using rheumatologist's review as a standard, the sensitivity of the algorithm was 100%, specificity was 88%, and the positive predictive value was 91%. The validation of rheumatologist's review by medical record showed 81% sensitivity, 60% specificity, and 78% positive predictive value. CONCLUSION: Reliability of rheumatologists' assignment of a diagnosis of RA by using self-report data is good. Algorithms defining symptoms as either joint swelling or tenderness with symptom duration >or=4 weeks have a better agreement with rheumatologist's diagnosis than do ones relying on a longer symptom duration. RELEVANCE: These findings have important implications for health services research and quality improvement interventions pertinent to case finding for RA through self-report data.
OBJECTIVE: To describe the development and evaluation of a patient self-report case-finding method for rheumatoid arthritis (RA) not dependent on direct contact with the treating physicians. METHODS: The American College of Rheumatology criteria for RA diagnosis were adapted for patient self-report using a questionnaire, and alternative scoring algorithms were evaluated to balance case-finding sensitivity and specificity. Positive rheumatoid factor tests were used to identify 1053 individuals in 2 large healthcare organizations; 440 agreed to receive study materials. Case-finding results were validated by medical record review (MRR) for a random sample of 90 patients. Three scoring algorithms were compared with MRR for likelihood of RA diagnosis. Cases not classifiable by algorithm were flagged and reviewed by 2 expert physicians for likelihood of RA diagnosis. RESULTS: Pilot testing demonstrated that patients comprehended the questionnaire and were willing to answer the questions. Completed questionnaires were returned by 265 (60%) of the 440 patients contacted. Following expert physician review of 16 flagged cases in the 90-patient MRR subsample, the most accurate scoring algorithm demonstrated 80% sensitivity, 67% specificity, 74% accuracy, and 77% positive predictive value for detecting early RA. CONCLUSION: The case-finding method represents a promising tool for identifying RA patients, with potential application in research and quality-assurance activities. RELEVANCE: This case-finding method should be useful in research and quality-assurance efforts requiring identification of RA patients treated by all types of providers in healthcare organizations in which centralized laboratory data are available.
OBJECTIVE: To quantitate patient retention and radiographic progression rates in serial hand/wrist radiographs of patients with rheumatoid arthritis (RA) who were not being treated with disease modifying antirheumatic drugs (DMARD). METHODS: A total of 1433 RA patients with 1-7 years' disease duration entered a 3-year prospective randomized double-blind clinical trial comparing the nonsteroidal antiinflammatory drugs (NSAID) etodolac (300 or 1000 mg daily) and ibuprofen (2400 mg daily). Standardized hand/wrist radiographs were obtained yearly and at dropout if > 6 months after entry. DMARD were not permitted. Joint erosion, joint space narrowing (JSN), and total scores of 3 readers were averaged. RESULTS: At entry, mean duration of RA was 3.5 years (range 1-7); ages were 21-78 years; patients were 71% female, 84% Caucasian, 67% rheumatoid factor (RF) positive; tender joint count was 29, swollen joint count 22, Westergren erythrocyte sedimentation rate (ESR) 49, and C-reactive protein (CRP) 2.44. There were 824 (57.5%) patients who completed >or= 6 months and had paired radiographs; 46% completed 48 weeks; 31%, 98 weeks; and 19%, 147 weeks. Months between paired radiographs (time in study) averaged 23.1 (range 6-36). Mean progression rates for total, erosion, and JSN scores (5.08, 2.53, and 2.54 units per year, respectively) were significantly associated with time in study, baseline RF, ESR, CRP, swollen joint count, presence of erosions at entry, and with 20% and 50% composite clinical responses. Painful joint count and RA duration were weakly associated only with progression of erosions. Progression rates were not associated with age, sex, corticosteroid use, or prior DMARD use. Patients who completed the 3-year trial had less severe disease activity and radiographic progression than those who dropped out. CONCLUSION: In this 3-year prospective double-blind clinical trial that prohibited DMARD, retention rates (57.5%, 46%, 31%, and 19% at 0.5, 1, 2, and 3 years) were similar to those in the non-DMARD-treated placebo groups of recent published studies. Radiographic progression rates are reported for 824 non-DMARD-treated patients during RA of 1-10 years' duration. This information may be useful as background information in the interpretation of longterm clinical trials that evaluate joint radiographic outcomes.
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