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Abstract
Background The new 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis (RA) aim at earlier diagnosis of RA compared to the 1987 ACR criteria.
Objective To evaluate the ability of the 2010 ACR/EULAR and the 1987 ACR classification criteria to predict radiographic progression after 10 years of follow-up.
Methods All early arthritis patients referred to Central Hospital in Jyväskylä from 1997 to 1999 (cases with peripheral joint synovitis, other specific diseases excluded) were included in this 10-year follow-up study. Radiographs of hands and feet were analysed according to Larsen on a scale of 0–100.
Results At 10 years, 58% of the patients had an erosive disease (defined as Larsen ≥2 in at least one joint). The discriminative power of the 2010 ACR/EULAR and the 1987 ACR criteria (erosive disease at 10 years) were comparable, with area under the curve 0.72 (95% CI 0.65 to 0.79) (2010 ACR/EULAR criteria) and 0.65 (95% CI 0.58 to 0.72) (1987 ACR criteria). The respective sensitivities and specificities were 0.87 and 0.70, and 0.44 and 0.47. At 10 years, median (IQR) Larsen score was 6 (0, 15) among patients who had fulfilled both sets of criteria, 2 (0, 8) in those who met the 2010 ACR/EULAR and did not meet the ACR 1987 criteria, 0 (0, 5) in those who met ACR 1987 criteria but did not meet 2010 ACR/EULAR criteria, and 0 (0, 2) among patients who did not fulfil either of the criteria. The percentage of patients with erosions was 69%, 64%, 32% and 26%, respectively.
Conclusions The ability of the 2010 ACR/EULAR and 1987 ACR classification criteria to identify erosive disease in early arthritis is low. The discriminative power of the 2010 ACR/EULAR criteria of erosiveness in 10 years is slightly better than that of the 1987 ACR criteria.
- Early Rheumatoid Arthritis
- Ant-CCP
- Rheumatoid Factor
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The 1987 classification criteria for rheumatoid arthritis (RA) were designed to improve the differential diagnosis of RA from other inflammatory joint diseases. They were adopted by the American College of Rheumatology (ACR) and have been widely used in RA studies.1
A common consensus for early initiation of treatment of RA exists. The 1987 RA classification criteria are not suitable for this strategy.2 Therefore, as a collaboration of ACR and the European League Against Rheumatism (EULAR), new classification criteria for RA were elaborated, and published in 2010.3
The old and new criteria have been compared in a few studies.4–6 Sensitivity of the 2010 ACR/EULAR criteria ranged from 0.58 to 0.85 and specificity from 0.50 to 0.86 depending on the outcome used: disease modifying drug (DMARD) use, methotrexate use, erosive disease, or expert opinion.7
The purpose of the current study was to compare the 2010 ACR/EULAR and the 1987 ACR criteria in predicting radiographic outcomes at 10 years in an early arthritis clinical cohort.
Patients and methods
Patients
All early arthritis patients older than 16 years referred to Central Hospital in Jyväskylä from 1997 to 1999 with a recent onset synovitis, not better explained by another disease, were included in the present cohort. The patients received rheumatology care in Jyväskylä Central Hospital for at least 2 years and subsequently were invited to take part in a 10-year follow-up visit.
A total of 221 out of 377 patients had all information required: radiographs of hands and feet at baseline and 10 years, joint counts, rheumatoid factor (RF), duration of symptoms, Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS28). Radiographs of hands and feet including metacarpophalangeal I–V, metatarsophalangeal (MTP) II–V, and wrists were scored according to Larsen et al8; the range of score was from 0 to 100.9 Erosive disease at 10 years was defined as Larsen score of ≥2 in at least one joint.8 Anti-citrullinated peptides (ACPAs) were not taken routinely at the time of diagnosis but were analysed later. As ACPAs have been shown to be very stable,10 we presumed that patients with ACPA positivity were also ACPA-positive at baseline.
Application of the 2010 ACR/EULAR criteria
The 2010 ACR/EULAR criteria were used as described by Aletaha et al.3
Application of the 1987 ACR criteria
According to the1987 ACR revised classification criteria for RA, four of the seven criteria had to be fulfilled for definite RA.1 The erosion criterion was also applied to the MTP II–V joints.
Statistical analysis
To evaluate the ability of the two sets of classification criteria to discriminate erosive disease at 10 years, receiver operating characteristic curves (ROC) with corresponding areas under the curves (AUC) were calculated. Performances of the two sets were also examined using sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios with 95% CI.
Results
Patients
At baseline, 221 of 377 patients with early arthritis were included, 164 patients (74%) fulfilled the 2010 ACR/EULAR criteria and 139 patients (63%) the 1987 ACR criteria, while 38 patients did not fulfil either of the two sets of classification criteria for RA. Baseline characteristics of the patients are presented in table 1.
Baseline characteristics of the 221 patients with early arthritis
A total of 156 patients were excluded from the study due to missing data: 80 patients died, 15 patients’ diagnosis was changed, diagnosis of 14 patients had been made in other hospitals and therefore baseline values were missing, three patients moved out of the area, and 44 patients were not willing to participate in the 10-year visit.
Patients with missing data (n=156) were older (mean age 61 vs 53; p<0.001), more disabled (mean HAQ 0.99 vs 0.77) and had shorter duration of symptoms (mean duration of symptoms 4 vs 6 months).
Treatment
DMARDs were started in all patients at diagnosis. Over the course of 10 years, 79% of the patients had been treated with methotrexate, 82% with sulphasalazine, 59% with hydroxychloroquine and 11% with biologicals; 64% of patients had also received low dose glucocorticoid therapy. Swollen joints were actively treated with local glucocorticoid injections.
Erosive disease
At 10 years, 58% of the patients had developed an erosive disease. At 10 years, median (IQR) Larsen score was 6 (0, 15) among patients who had fulfilled both sets of criteria, 2 (0, 8) in those who met the 2010 ACR/EULAR and did not meet the ACR 1987 criteria, 0 (0, 5) in those who met ACR 1987 criteria but did not meet 2010 ACR/EULAR criteria, and 0 (0, 2) among patients who did not fulfil either criteria (figure 1). Percentage of patients with erosions were 69%, 64%, 32% and 26%, respectively.
Predictive value of the two different sets of classification criteria for rheumatoid arthritis for erosive disease at 10 years. Box plot of Larsen index showing the median, the 25% and 75% percentiles, and the lowest and highest values that are not outliers. Outliers are indicated by ° and extreme values by *.
Prediction of erosions
Among patients who fulfilled the 2010 ACR/EULAR criteria at baseline, 69% had erosions at 10 years. A total of 57 patients did not reach the score of 6 in the 2010 ACR/EULAR criteria, 16 (28%) of which were erosive at 10 years. Three patients were already erosive at baseline; they fulfilled the 2010 ACR/EULAR criteria.
Among the patients who were 1987 ACR positive at baseline, 64% were erosive at 10 years; 46% of the patients developed erosions among those who were 1987 ACR negative at baseline.
The AUC of the ROC curves show similar performance for the two sets of criteria in the discrimination of erosive disease (table 2). In both criteria sets, sensitivity was high (0.87 and 0.70) but specificity was low (0.44 and 0.47) (table 2).
Performance of the two sets of classification criteria for rheumatoid arthritis to predict an erosive disease at 10 years
Discussion
Radiographic progression of an individual with early arthritis cannot be predicted by any of the so far published sets of criteria for RA, and they should not be used in clinical practice as a criterion to initiate effective treatment. The 2010 ACR/EULAR classification criteria for RA are superior to the 1987 ACR criteria for the selection of early arthritis patients for clinical trials, and according to our results they seem to work slightly better than the 1987 ACR criteria in predicting erosions at 10 years.
The rheumatological community is unanimous with respect to the strategy focusing on early and active DMARD treatment.2 ,11 As shown in previous studies, the use of the 2010 ACR/EULAR4–6 criteria classified more patients as RA than the 1987 ACR criteria. Accordingly, the newer criteria better serve the present drug treatment strategy than the more strict criteria designed in 1987.
Nevertheless, as shown in figure 1, the few patients fulfilling neither of the classification criteria at baseline developed prominent radiographic joint damage at 10 years. In daily clinical practice, the patients with early arthritis without a definite diagnosis must not be diagnosed according to any of the formally accepted criteria, but all cases should be considered as candidates of poor prognosis and treated accordingly. Therefore, in daily clinical work, we might forget criteria and start active DMARD therapy with methotrexate at once. Furthermore, in those patients with signs of poor prognosis (high RF or ACPA, high disease activity or erosions at baseline),12 ,13 therapy should be started with a combination of traditional DMARDs including methotrexate and a low-dose glucocorticoid.
Britsemmer et al14 studied the power of the 2010 ACR/EULAR criteria to identify patients with erosive disease in 455 patients with early arthritis. Radiographs at 3 years were available from 175 patients. The median (IQR) Sharp–van der Heijde score was 0 (0, 0) at baseline and 0 (0, 4) at 3 years. The ability of the 2010 ACR/EULAR criteria to identify patients with erosive disease was low. In the study the patients with typical erosion were not classified as RA unless they did not receive a score from 6 to 10 in 2010 ACR/EULAR criteria. We followed the same strategy, because typical erosion of RA has not been defined in the criteria.
The strength of our study is that all early arthritis patients were included. The weakness, on the other hand, was that due to long follow-up time, the radiographs of all patents were not available. Although the study was started in 1997, treatment might have influenced our results.
In conclusion, the study suggests that the 2010 ACR/EULAR and the 1987 classification criteria predict poorly erosive disease in patients with early RA. However, the discriminative power of the 2010 ACR/EULAR criteria of erosiveness in 10 years is slightly better than that of the 1987 ACR criteria.
References
Footnotes
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Contributors All authors contributed to the work.
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Funding Competitive Research Funding of Tampere University Hospital.
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Competing interests None.
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Patient consent Obtained.
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Ethics approval Ethics Committee of Jyväskylä Central Hospital.
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Provenance and peer review Not commissioned; externally peer reviewed.