Do magnetic resonance imaging-detected erosions predict progression to rheumatoid arthritis in patients presenting with clinically suspect arthralgia? A longitudinal study.

Objective: Radiographic joint erosions are a hallmark of rheumatoid arthritis (RA). Magnetic resonance imaging (MRI) is more sensitive than radiographs in detecting erosions. It is unknown whether MRI-detected erosions are predictive for RA development in patients with clinically suspect arthralgia (CSA). Therefore, we investigated the prognostic value of MRI-detected erosions, defined as any MRI erosion, or MRI erosion characteristics that were recently identified as specific for RA in patients with evident arthritis. Method: Patients presenting with CSA (n = 490) underwent contrast-enhanced 1.5 T MRI of the wrist, metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints. MRIs were scored according to the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system (RAMRIS). Presence of any MRI erosion (present in < 5% of symptom-free controls) and RA-specific erosion characteristics as identified previously (grade ≥ 2 erosions, erosions in MTP5, erosions in MTP1 if aged < 40 years) were studied with clinically apparent inflammatory arthritis development as outcome. Analyses were corrected for age and MRI-detected subclinical inflammation. Results: Erosions were present in 20%. Presence of any MRI erosion was not associated with arthritis development [multivariable analysis hazard ratio (HR) 0.97 (95% confidence interval 0.59-1.59)]. The different RA-specific erosion characteristics were not predictive [grade ≥ 2 HR 1.05 (0.33-3.34), erosions in MTP5 HR 1.08 (0.47-2.48), and MTP1 if aged < 40 years HR 1.11 (0.26-4.70)]. Erosion scores were higher in anti-citrullinated protein antibody (ACPA)-positive than in ACPA-negative patients (median 2.0 vs 1.0, p = 0.002), and related to more subclinical inflammation. Within both subgroups, MRI erosions were not predictive. Conclusions: MRI-detected erosions in hands and feet were not predictive for inflammatory arthritis development. Therefore, evaluating MRI for erosions in addition to subclinical inflammation does not provide added clinical value in CSA.

Contribution of tenosynovitis of small joints to the symptom morning stiffness in patients presenting with undifferentiated and rheumatoid arthritis.

Objective: Morning stiffness (MS) is characteristic of rheumatoid arthritis (RA). Despite its association with functional disability, the extent to which local inflammatory processes contribute to this symptom is unknown. Magnetic resonance imaging (MRI)-detected tenosynovitis of small joints is recognized as an early feature of RA, which is also associated with functional impairments. It has been proposed that tenosynovitis contributes to MS. Therefore, we assessed the relationship between MS and MRI-detected inflammation, in particular tenosynovitis.Method: In total, 286 consecutive patients newly presenting with undifferentiated arthritis and RA underwent contrast-enhanced 1.5 T MRI of (2-5) metacarpophalangeal, wrist, and (1-5) metatarsophalangeal joints. Scans were scored for tenosynovitis according to Haavardsholm, and for synovitis by Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS). MS was dichotomized as ≥ 60 min or not. Associations between MS and tenosynovitis/synovitis were tested with logistic regression, data were categorized (solitary or simultaneous presence of synovitis/tenosynovitis), and the presence of an additive interaction was assessed.Results: MS was present in 40% of patients. Tenosynovitis was more often present in patients with MS than without MS [80% vs 65%, odds ratio (OR) 2.11, 95% confidence interval (1.21;3.69)]. Synovitis was more often present in patients with MS [58% vs 44%, OR 1.79 (1.11;2.91)]. In categorized analyses, concurrent synovitis and tenosynovitis had the largest association [OR 2.43 (1.30;4.54)], in contrast to solitary synovitis [OR 0.85 (0.21;3.47)]. The additive interaction was non-significant. The variance explained in all analyses was small (range 4-5%).Conclusion: Tenosynovitis, combined with synovitis, at small joints is associated with MS and contributes to the pathophysiology of MS.

What is the additional value of MRI of the foot to the hand in undifferentiated arthritis to predict rheumatoid arthritis development?

BACKGROUND: MRI-detected subclinical joint inflammation in the hand joints of patients with undifferentiated arthritis (UA) predicts progression to rheumatoid arthritis (RA). It is unknown if adding MRI of the foot increases predictive accuracy compared to the hand alone. METHODS: 1.5-T contrast-enhanced MRI of the unilateral foot (MTP-1-5) and hand (MCP-2-5 and wrist) was performed in 123 patients presenting with UA (not fulfilling the 2010 RA criteria) and scored for bone marrow edema (BME), synovitis and tenosynovitis. Symptom-free controls (n = 193) served as a reference for defining an abnormal MRI. Patients were followed for RA development ≤ 1 year, defined as fulfilling the classification criteria or initiation of disease-modifying antirheumatic drugs because of the expert opinion of RA. The added predictive value of foot MRI to hand MRI was evaluated. RESULTS: Fifty-two percent developed RA. Foot tenosynovitis was predictive (OR 2.55, 95% CI 1.01-6.43), independent of BME and synovitis (OR 3.29, 95% CI 1.03-10.53), but not independent of CRP and number of swollen joints (OR 2.14, 95% CI 0.77-5.95). Hand tenosynovitis was also predictive independent of BME and synovitis (OR 3.99, 95% CI 1.64-9.69) and independent of CRP and swollen joints (OR 2.36, 95% CI 1.04-5.38). Adding foot tenosynovitis to hand tenosynovitis changed the sensitivity from 72 to 73%, specificity from 59 to 54% and AUC from 0.66 to 0.64; the net reclassification index was - 3.5. CONCLUSION: MRI-detected tenosynovitis of the foot predicts progression to RA. However, adding MRI of the foot does not improve the predictive accuracy compared to MRI of the hand alone. In view of cost reduction, the performance of foot MRI for prognostic purposes in UA can be omitted.

Does the presence of magnetic resonance imaging-detected osteitis at diagnosis with rheumatoid arthritis lower the risk for achieving disease-modifying antirheumatic drug-free sustained remission: results of a longitudinal study.

BACKGROUND: Although infrequent, some rheumatoid arthritis (RA) patients achieve disease-modifying antirheumatic drug (DMARD)-free sustained remission. The absence of RA-specific autoantibodies, such as anticitrullinated protein antibodies (ACPA), is known to be associated with this outcome but further mechanisms underlying the chronic nature of RA are largely unknown. Magnetic resonance imaging (MRI)-detected bone marrow edema (BME), or osteitis, strongly predicts erosive progression and is associated with ACPA positivity. Therefore, we hypothesized that the presence of MRI-detected osteitis is also predictive of not achieving DMARD-free sustained remission and that the presence of osteitis mediates the association between ACPA and DMARD-free sustained remission. METHODS: A 1.5 T unilateral hand and foot MRI was performed at disease presentation in 238 RA patients, evaluating BME, synovitis, and tenosynovitis (summed as MRI inflammation score). DMARD-free sustained remission, defined as the absence of clinical synovitis after DMARD cessation that persisted during the total follow-up, was assessed (median follow-up 3.8 years). Associations between the different MRI-detected inflammatory features and this outcome were studied. A mediation analysis was performed to study whether the presence of BME mediated the association between ACPA and DMARD-free sustained remission. Finally, patterns of MRI-detected inflammation with regard to DMARD-free sustained remission were studied using partial least squares (PLS) regression. RESULTS: Forty-six (19.3%) patients achieved DMARD-free sustained remission. ACPA positivity associated independently with remission (hazard ratio (HR) 0.16, 95% confidence interval (CI) 0.06-0.39). In contrast, no associations were observed between MRI-detected BME (HR 0.99, 95% CI 0.94-1.03), or other MRI inflammatory features, and achieving DMARD-free sustained remission. Thus, the presence of BME did not mediate the association between ACPA and DMARD-free sustained remission. Furthermore, a PLS analysis revealed that patients who did or did not achieve remission could not be distinguished by patterns of MRI-detected inflammation. CONCLUSIONS: At disease presentation, osteitis, as well as other MRI-detected inflammatory features, was not associated with achieving DMARD-free sustained remission over time. Thus, imaging predictors for joint damage and disease persistence differ. The processes mediating RA chronicity remain largely unsolved.