Wouter P. Nieuwenhuis

Evaluation of Magnetic Resonance Imaging–Detected Tenosynovitis in the Hand and Wrist in Early Arthritis

Magnetic resonance imaging (MRI) is a sensitive method to detect inflammation in rheumatoid arthritis (RA), visualizing synovitis, bone marrow edema, and tenosynovitis. The prevalence of MRI‐detected tenosynovitis and its diagnostic value in early arthritis are unclear. This study was undertaken to identify the frequency of MRI‐detectable tenosynovitis at the metacarpophalangeal (MCP) and wrist joints in early arthritis and the association of these with RA and the severity of RA.

The Course of Bone Marrow Edema in Early Undifferentiated Arthritis and Rheumatoid Arthritis: A Longitudinal Magnetic Resonance Imaging Study at Bone Level.

In patients with rheumatoid arthritis (RA), bone marrow edema (BME) scores are associated with development of erosions. However, little is known about the course and outcome of BME at bone level. We undertook this study to determine the association of BME and synovitis with the development of erosions in the same bone longitudinally.

Using a reference when defining an abnormal MRI reduces false-positive MRI results—a longitudinal study in two cohorts at risk for rheumatoid arthritis

Objectives The use of hand and foot MRI in the diagnostic process of RA has been advocated. Recent studies showed that MRI is helpful in predicting progression from clinically suspect arthralgia (CSA) to clinical arthritis, and from undifferentiated arthritis (UA) to RA. Symptom-free persons can also show inflammation on MRI. This study aimed to evaluate if MRI findings in symptom-free volunteers are relevant when defining a positive MRI. Methods Two hundred and twenty-five CSA patients and two hundred and one UA patients underwent MRI of MCP, wrist and MTP joints at baseline and were followed for 1 year on progression to arthritis and RA, respectively, as reported previously. MRI was considered positive if ⩾ 1 joint showed inflammation (called uncorrected definition), or if ⩾ 1 joint had inflammation that was present in < 5% of persons of the same age category at the same location (called 5% corrected definition). Test characteristics were compared for both definitions. Results By using MRI data of symptom-free volunteers as reference, specificity of MRI-detected inflammation increased from 22 to 56% in CSA patients, and from 10 to 36% in UA patients. The sensitivity was not affected; it was 88 and 85% in CSA patients and 93 and 93% in UA patients. The accuracy also increased, from 32 to 60% in CSA patients and 22 to 44% in UA patients. Conclusion The use of a reference population resulted in a substantial reduction of false-positive results, without influencing the sensitivity. Although common for other tests in medicine, this phenomenon is novel for MRI in the early detection of RA.

Changes in the clinical presentation of patients with rheumatoid arthritis from the early 1990s to the years 2010: earlier identification but more severe patient reported outcomes

The relevance of early identification of rheumatoid arthritis (RA) is acknowledged for several decades. Over time the interpretation of early has changed: in the early 1990s a symptom duration <2 years was considered early. Nowadays earlier identification is recommended,1 some suggest that identification within 12 weeks after symptom onset is optimal. In this study, we evaluated the presentation of RA over the past decennia. We assessed whether patients with RA were recognised earlier and if this affected the phenotype of RA at first presentation. We observed that patients with RA are indeed identified after a shorter symptom duration, that this was paralleled with less severe inflammation at presentation, but paradoxically also with increased severity of patient reported outcomes (PROMs). All patients in the Leiden Early Arthritis Clinic (EAC) cohort that fulfilled the 2010 European League Against Rheumatism/American College of Rheumatology RA criteria were studied (n=1406).2 ,3 In short, the EAC was started in 1993 and inclusion criteria …

Evaluation of the diagnostic accuracy of hand and foot MRI for early Rheumatoid Arthritis

Objectives To assess the diagnostic value of MRI for early RA. In some RA patients, a classifiable diagnosis cannot be made at first presentation; these patients present with unclassified arthritis (UA). The use of MRI for early diagnosis of RA is recommended, yet the evidence for its reliability is limited. Methods MRI of hand and foot was performed in 589 early arthritis patients included in the Leiden Early Arthritis Clinic (229 presented with RA, 159 with other arthritides and 201 with UA). Symptom-free controls provided a reference for defining an abnormal MRI. In preliminary investigations, MRI of patients who presented with RA was compared with MRI of symptom-free controls and of patients with other arthritides. Thereafter, the value of MRI in early RA diagnosis was determined in UA patients using the 1-year follow-up on fulfilling the 1987 RA criteria and start of disease-modifying drugs as outcomes. Results Preliminary investigations were promising. Of the UA patients, 14% developed RA and 37% started disease-modifying treatment. MRI-detected tenosynovitis was associated with RA development independent of other types of MRI-detected inflammation [odds ratio (OR) = 7.5, 95% CI: 2.4, 23] and also independent of age and other inflammatory measures (swollen joints, CRP) (OR = 4.2, 95% CI: 1.4, 12.9). Within UA patients, the negative predictive value of abnormal tenosynovitis was 95% (95% CI: 89%, 98%) and the positive predictive value 25% (95% CI: 17%, 35%). The performance was best in the subgroup of UA patients presenting with oligoarthritis (18% developed RA): the positive predictive value was 36% (95% CI: 23%, 52%), the negative predictive value was 98% (95% CI: 88%, 100%), the sensitivity was 93% (95% CI: 70%, 99%) and the specificity was 63% (95% CI: 51%, 74%). Conclusion MRI contributes to the identification of UA patients who will develop RA, mostly in UA patients presenting with oligoarthritis.

Does adding the presence of MRI detected bone marrow oedema improve the accuracy of the 2010 EULAR/ACR criteria for rheumatoid arthritis?

With great interest we read the letter of Tamai et al who studied whether adding information obtained by MRI of wrist and metacarpophalangeal (MCP) joints to the existing 2010 European League against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for rheumatoid arthritis (RA) was helpful in improving the accuracy of these criteria. The study population was patients with undifferentiated arthritis according to the 1987 classification criteria. Two outcomes were studied: fulfilling the 1987 classification criteria for RA after 1-year of disease and the start of disease-modifying antirheumatic drugs (DMARDs) within the first year.1 The results on MRI detected bone marrow oedema (BME) added to the 2010 criteria with the start of DMARDs as outcome were most interesting. The sensitivity and specificity of the 2010 criteria without addition of BME were 61.9% and 82.6% respectively and the accuracy 70.5%. After adding information on BME, an increase in sensitivity and accuracy was observed (76.3% and 75.9%, respectively); this was accompanied by a decline in specificity (75.4%). Area under receiver operator characteristic curves (AUCs) were not reported.1 It is known that the …

SAT0041 The Course of Bone Marrow Edema in Early Undifferentiated and Rheumatoid Arthritis; A Longitudinal MRI Study on Bone Level

Background In rheumatoid arthritis (RA) patients, bone marrow edema (BME)-scores are associated with development of erosions. However, little is known on the course and outcome of BME at bone level. Therefore this study determined the association of BME and MRI-synovitis in the same bone longitudinally. Objectives This study was aimed to determine the course of BME and MRI-synovitis at bone level. Furthermore the association between the course of BME and local synovitis and the development of erosions in the same bone was studied. Methods 1,947 bones of MCP, wrist and MTP-joints of 59 patients presenting with rheumatoid or undifferentiated arthritis were studied using 1.5T MRI at baseline, after four and twelve months. Scanning and scoring of BME, synovitis and erosions were performed according to RAMRIS. The relation of the course of BME and synovitis to erosive progression at bone level during 1-year was evaluated. Results Of the bones showing BME at baseline (n=203), BME persisted in 56%, disappeared in 39%, and disappeared-reappeared seldom (5%). Stratified analyses at baseline revealed that BME was associated with erosive progression, in presence and in absence of local synovitis (ORs 7.5 95%CI 3.8-14.9 and 6.9 95%CI 1.9-25.6). Local synovitis, however, was not associated with erosive progression (OR 2.0 95%CI 0.6-7.0 in presence of BME and 1.9 95%CI 0.8-4.1 in the absence of BME). In multivariable GEE-analyses, persistent BME was strongly associated with erosive progression (OR 60 95%CI 17-318), in contrast to persistent synovitis (OR 1.4 95%CI 0.4-5.3). Conclusions BME frequently persists during the first year. Persistent BME was strongly associated with erosive progression in the same bone, independent of local synovitis. No independent association was observed for persistent synovitis. These findings are relevant for the comprehension on the development of erosions in RA. Disclosure of Interest None declared

Is the Modified Disease Activity Score Superior to the Disease Activity Score in Early Arthritis and Rheumatoid Arthritis? Comment on the Article by Baker et al

To the Editor: We read with great interest the recent article by Baker et al, in which the authors describe the development of a modified Disease Activity Score (M-DAS) based on correlations with concurrent synovitis scores as measured by magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA) (1). The original DAS was developed in the early 1990s based on the clinical findings of rheumatologists; it consists of the Ritchie Articular Index, the number of swollen joints, the erythrocyte sedimentation rate (ESR), and the patient’s global assessment of disease activity measured on a visual analog scale (PtGA). Since then, the DAS has been modified and validated several times, including for use with the C-reactive protein level (DAS-CRP) instead of the ESR and for use with smaller joint counts (28-joint count DAS [DAS28]). In the recently developed M-DAS, tender joint count (TJC) and PtGA, the variables that are most subject to subjectivity, are no longer included, and the evaluator’s global assessment (EvGA) is included. The M-DAS was developed using data from the GO-BEFORE study and validated using data from the GOFORWARD study (both RA clinical trials). Compared to the DAS28, correlations between MRI-detected synovitis and the M-DAS28 were superior, and the M-DAS28 was shown to be a more precise predictor of radiographic progression (1). Similarly, modified versions of the Simplified Disease Activity Index (M-SDAI) and Clinical Disease Activity Index (M-CDAI) were derived (1). These modified measures need to be evaluated in independent studies to determine their validity. We therefore compared the original and modified measures in a population-based inception cohort of patients with early arthritis, using MRI-detected inflammation (synovitis and bone marrow edema) and radiographic progression as outcomes. Baseline MRI data and DAS28 scores of 127 patients with early arthritis, included in the Leiden Early Arthritis Cohort between 2010 and 2012, were available; of these patients, 91 had data on EvGA. The cohort and the details of the MRI protocol are described elsewhere (2). Using the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system, 2 readers scored MRIs for synovitis and bone marrow edema. The total synovitis and bone marrow edema scores of the metacarpophalangeal and wrist joint were calculated using the mean scores. Within-reader intraclass correlation coefficients (ICCs) for inflammation on MRI were 0.99 and 0.93 for the 2 readers, respectively; the between-reader ICC was 0.87 (2). Patients were followed up prospectively. Radiographs of the hands and feet of 87 patients were taken at baseline and after 1 year, and 1 reader chronologically scored the joints using the Sharp/van der Heijde scoring (SHS) method (withinreader ICC 0.86). Progression was defined as an increase in SHS of 1 (similar to the definition used by Baker et al). Sensitivity analyses defining progression as SHS of 3 were also performed. The following formulas were used: DAS28CRP (0.56 TJC28) (0.28 SJC28) 0.36 ln([CRP 10] 1) 0.14 (PtGA 0.96) and M–DASCRP (0.49 ln[CRP]) (0.15 SJC28) (0.22 EvGA), where SJC28 is the swollen joint count in 28 joints and ln(CRP) is the linear log-transformed CRP. When the CRP was 1 mg/dl, the linear log-transformed CRP was negative and was set to 0. The formulas used to calculate the CDAI and SDAI correspond to those used by Baker et al. Correlations between disease activity scores and MRI-detected inflammation were determined using the Pearson correlation coefficient. Superiority of correlation coefficients (which were obtained in the same samples) was determined using the “corcor” command in Stata software. Areas under the curve (AUCs) were determined for the association with radiographic progression; differences in the AUC were compared using the “roccomp” Stata command. Of the 127 patients with early arthritis, 58% were women and 28% were anti–citrullinated protein antibody (ACPA) positive. The mean age was 55.6 years, the median symptom duration at presentation was 13 weeks, the median SJC was 3, the median TJC was 4, the median ESR was 21.8 mm/hour, the median CRP level was 0.4 mg/dl, the median synovitis score on MRI was 3.5, and the median bone marrow edema score on MRI was 3.5. Radiographic progression ( SHS 1) was present in 41% ( SHS 3 in 17%). Fifty-one patients with early arthritis fulfilled the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for RA (3); these patients had a median SJC of 3, a median TJC of 4, a median CRP level of 0.8 mg/dl, and a median ESR of 25 mm/hour; 69% were ACPA positive, 46% had a SHS of 1, and 17% had a SHS of 3. Correlations of the original scores and the modified scores with MRI-evident synovitis are shown in Table 1. The correlation coefficients for the modified disease activity scores were slightly higher than those for the DAS28-CRP and DAS28ESR (0.32 and 0.31 for the M–DAS-CRP and the DAS28CRP, respectively, and 0.36 and 0.34 for the M–DAS-ESR and the DAS28-ESR, respectively); these differences were not statistically significant. For the correlation between bone marrow edema and the M-DAS28 and the DAS28, correlation coefficients were slightly higher for the M-DAS28 (Table 1), but were not significantly different. When comparing the M–DAS28-CRP and DAS28-CRP with radiographic progression ( SHS 1) as the outcome, the AUCs were slightly higher for the M-DAS28 (0.54 versus 0.49, respectively). The same was true for the M–DAS28-ESR versus the DAS28-ESR (0.56 versus 0.50, respectively) (Table 1). These differences did not yield statistical significance either. When defining radiographic progression as SHS 3, similar results were obtained (data not shown). Analysis of the 51 patients who fulfilled the 2010 classification criteria for RA resulted in comparable findings; the M-DAS28 scores were not significantly better than the DAS28 scores (Table 1). When analyzing the M-CDAI and M-SDAI, no significant improvements were obtained compared to the original CDAI and SDAI (Table 1). In conclusion, we observed that the differences between the correlation coefficients for the M-DAS28 and the

Are MRI-detected erosions specific for RA? A large explorative cross-sectional study

Objectives MRI is recommended in the diagnostic process of rheumatoid arthritis (RA) to detect joint damage early. MRI-detected erosions are also present in symptom-free controls, especially at older age. It is unclear if RA-specific MRI-detected erosions can be distinguished from ‘physiological’ erosions in symptom-free individuals. This study compared MRI-detected erosions of patients with RA with healthy controls and with other arthritides. Methods 589 newly presenting patients with early arthritis (238 RA, 351 other arthritides) and 193 symptom-free controls underwent contrast-enhanced 1.5T MRI of unilateral metacarpophalangeal and metatarsophalangeal (MTP) joints. Total erosion score (according to the Rheumatoid Arthritis MRI Scoring System), number, severity, location of erosions and simultaneous presence of MRI-detected inflammation (synovitis and/or bone marrow oedema) were compared; participants were categorised in three age groups (<40, 40–59, ≥60). Results Patients with RA had statistically significant higher total erosion scores than controls but scores of individual persons largely overlapped. Grade ≥2 erosions and MTP5 erosions were specific for RA (specificity 98%–100% and 90%–98% for different age groups). MTP1 erosions were only specific if aged <40 (specificity 98%) and erosions with inflammation if aged <60 (specificity 91%–100%). ≥1 of the mentioned erosion characteristics were present in 29% of patients with RA. Comparing patients with RA with other arthritides revealed that grade ≥2 erosions and MTP5 erosions remained specific for RA (specificity ≥89%) as well as MTP1 erosions if aged <40 (specificity 93%), in contrast to erosions combined with inflammation (specificity 49%–85%). Conclusions Total erosion scores of individual persons were largely overlapping. Erosion characteristics specific for RA were identified, but were infrequently present. Caution is needed not to overestimate the value of MRI erosions in the diagnostic process.

THU0032 Diagnostic Accuracy of Hand and Foot MRI for Early Rheumatoid Arthritis

Background Early diagnosis and treatment of rheumatoid arthritis (RA) is advocated. However, in part of the RA-patients a classifiable diagnosis cannot be made at first presentation; these patients present with unclassified arthritis (UA). The use of MRI for early diagnosis of RA is recommended, yet the evidence is limited. Objectives To assess the performance of hand and foot MRI for early diagnosis of RA. Methods Unilateral contrast-enhanced 1.5T MRI of the hand and foot was performed in 589 early arthritis patients included in the Leiden Early Arthritis Clinic, of whom 229 presented with RA, 159 with other arthritides and 201 with UA. MRI-findings observed in symptom-free controls served as reference to define an abnormal MRI. In preliminary investigations, patients that presented with RA were compared with symptom-free controls and with patients that presented with other arthritides. Thereafter, the accuracy of MRI was determined in UA-patients that were followed for 1-year on fulfilling the 1987-RA-criteria (primary outcome); the secondary outcome was start of disease-modifying drugs. Results The results of the preliminary investigations were promising and showed that MRI-detected tenosynovitis was more discriminative than other types of MRI-inflammation. Of all UA-patients, 29 (14%) developed RA and 75 (37%) started disease-modifying treatment. MRI-detected tenosynovitis was associated with RA-development independent of other types of MRI-inflammation (odds ratio (OR) 7.5 95%CI 2.4–23) and also independent of age and commonly used measures of inflammation (number of swollen joints and C-reactive protein) (OR 4.2 95%CI 1.4–12.9). Within UA-patients, the negative predictive value (NPV) of abnormal tenosynovitis was 95% and the positive predictive value (PPV) 25%. The performance was best in the subgroup UA-patients presenting with oligo-arthritis (18% developed RA): PPV was 36%, NPV 98%, sensitivity 93%, and specificity 63%. Decision curve analysis revealed a higher net benefit for a model including MRI-detected tenosynovitis. Conclusions MRI-detected inflammation, MRI-detected tenosynovitis in particular, contributes to identification of the UA-patient that will develop RA. Disclosure of Interest None declared