Improvement of symptoms in clinically suspect arthralgia and resolution of subclinical joint inflammation: a longitudinal study in patients that did not progress to clinical arthritis

INTRODUCTION: Arthralgia and MRI-detected subclinical inflammation can precede the development of clinically evident rheumatoid arthritis (RA). However, part of the patients presenting with clinically suspect arthralgia (CSA) do not progress to RA. In these 'non-progressors', we aimed to study the frequencies of spontaneous improvement of arthralgia and its relation with the course of subclinical inflammation. METHODS: Between April 2012 and April 2015, 241 patients were considered at risk for RA based on the clinical presentation and included in the CSA cohort. One hundred fifty-two patients with complete data on clinical follow-up did not develop clinical arthritis, of which 98 underwent serial 1.5T MRI scans (wrist, MCP2-5, and MTP1-5 joints) at baseline and after 2 years. MRI scans were scored for synovitis, tenosynovitis, and bone marrow oedema (summed: MRI inflammation score). MRI scores were compared to scores of symptom-free persons. RESULTS: After a 2-year follow-up, 33% of the 'non-progressors' had complete resolution of symptoms; 67% had no symptom resolution and were diagnosed as persistent CSA (44%), osteoarthritis (10%), and tendinomuscular complaints (13%). With symptom-free controls as a reference, patients without resolution did not have increased MRI scores at any time point. However, patients achieving resolution of symptoms had increased MRI inflammation scores at baseline (4.0 vs. 2.6, p = 0.037), but not after 2 years (3.0 vs. 2.6; p = 0.57), and during follow-up, their MRI inflammation score decreased significantly (p = 0.036). CONCLUSIONS: A subgroup of CSA patients that did not progress to RA had spontaneous improvement of symptoms and resolution of subclinical joint inflammation. This time relationship suggests that symptoms and inflammation were causally related in these patients. Further research is needed to identify the mechanisms underlying the resolution of inflammation

Body mass index and extent of MRI-detected inflammation: opposite effects in rheumatoid arthritis versus other arthritides and asymptomatic persons

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

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 rem

Functional limitations in the phase of clinically suspect arthralgia are as serious as in early clinical arthritis; a longitudinal study

Introduction A phase of arthralgia may precede the emergence of rheumatoid arthritis (RA). Although several studies have focused on biomarkers, the relevance of this phase for patients is less studied. It is unknown if patients already have functional limitations and if this is correlated to the extent of subclinical inflammation. Therefore, we assessed functional disability in patients with clinically suspect arthralgia (CSA), its association with MRI-detected subclinical inflammation and its course during progression to clinical arthritis.Methods From April 2012 to March 2015, 241 patients had arthralgia for Results The median HAQ score at presentation with CSA was 0.50. Higher MRI-inflammation scores were associated with higher HAQ scores (β=0.017, 95% CI=0.004 to 0.030). During median 103 weeks follow-up, 44 patients progressed to clinical arthritis. HAQ scores ≥1.0 were associated with arthritis development (HR=2.50, 95% CI=1.03 to 6.10). Within converters, median HAQ scores did not increase from presentation with CSA to arthritis development (0.88 and 0.75, p=0.36). Conclusions HAQ scores ≥1.0 at presentation were associated with the development of clinical arthritis. Functional limitations in the prearthritis phase of CSA were as serious as in the early clinical phase, demonstrating the relevance of CSA from patients’ perspectivesImaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Comprehending the symptomatic phase preceding rheumatoid arthritis: Clinically suspect arthralgia

This thesis focused on investigating the early identification of Rheumatoid Arthritis (RA), assessing the burden of disease, and enhancing understanding of disease mechanisms in the earliest disease phases. Many of the studies in this thesis focused on data from the Leiden Clinically Suspect Arthralgia (CSA) cohort. The CSA cohort is an inception cohort at the rheumatology outpatient clinic of the Leiden University Medical Centre, in Leiden, the Netherlands. CSA patients had recent-onset (We showed that although early identification is increasingly improving, there remains a large proportion of patients that cannot be accurately identified despite a suspect pattern of signs and symptoms, as well as information on autoantibodies. Furthermore, the burden of disease is already substantial during the symptomatic pre-arthritis phase of CSA. Future studies will have to provide evidence for the effectiveness of preventing persistent RA and functional disability with prescribing Disease-modifying antirheumatic drugs (DMARD) treatment in the phase of CSA. Dutch Arthritis Foundation (Reumafonds), ChipSoft, PfizerLUMC / Geneeskund

MRI in the earliest phases of rheumatoid arthritis

This thesis focussed on inflammation observed on magnetic resonance imaging (MRI) in the early phases of rheumatoid arthritis (RA) and was divided into two parts. In the first part we explored the prevalence of inflammation and erosions detected on MRI in the general population. In the second part, we studied the early phases of RA and assessed factors which could be associated with radiographic joint damage or local inflammation detected on MRI.LUMC / Geneeskund

Whole-body MRI of patients with polymyalgia rheumatica identifies a distinct subset with complete patient-reported response to glucocorticoids

Objectives: To determine whether whole-body MRI defines clinically-relevant subgroups within polymyalgia rheumatica (PMR) including glucocorticoid responsiveness. Methods: 22 patients with PMR and 16 with rheumatoid arthritis, untreated and diagnosed by consultant rheumatologists, underwent whole-body, multiple-joint MRI, scored by two experts. PMR patients reported whether they felt “back to normal” on glucocorticoid therapy and were followed for a median of 2 years. Results: All PMR patients were deemed to respond to glucocorticoids clinically. A characteristic pattern of symmetrical, extracapsular inflammation, adjacent to greater trochanter, acetabulum, ischial tuberosity and/or symphysis pubis, was observed in 14/22 of the PMR cases. In PMR, this pattern was associated with complete glucocorticoid response (p=0.01), higher pre-treatment C-reactive protein (CRP) and serum IL-6, and better post-treatment fatigue and function. Only 1/14 in the extracapsular group could stop glucocorticoids within 1 year, compared to 4/7 of the others. A score derived from the five sites discriminating best between PMR and RA correlated with IL-6 (p<0.002). IL-6 levels ≥16.8 pg/mL had 86% sensitivity and 86% specificity for the extracapsular MRI pattern. Conclusions: A subset of patients with rheumatologist-diagnosed PMR had a characteristic, extracapsular pattern of MRI inflammation, associated with elevated IL-6/CRP and with complete patient-reported glucocorticoid responsiveness

Moderate use of alcohol is associated with lower levels of C reactive protein but not with less severe joint inflammation: a cross-sectional study in early RA and healthy volunteers

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Baseline Objective Inflammation by Magnetic Resonance Imaging as a Predictor of Therapeutic Benefit in Early Rheumatoid Arthritis With Poor Prognosis

Objective: High magnetic resonance imaging (MRI )–detected inflammation is associated with greater progression and poorer outcomes in rheumatoid arthritis (RA ). This analysis aimed to determine if baseline MRI inflammation was related to clinical response and remission in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT ) study. Methods: AVERT was a phase III b, randomized, controlled trial with a 12‐month, double‐blind treatment period enrolling patients with early (≤2 years' duration), anti‐citrullinated peptide–positive methotrexate (MTX )‐naive RA . In this post hoc analysis, patients in the abatacept plus MTX (n = 114) and MTX (n = 111) arms with available MRI results were stratified into low and high baseline MRI inflammation groups based on previously developed cutoffs of synovitis and osteitis on unilateral hand–wrist contrast‐enhanced MRI . Simplified Disease Activity Index (SDAI ) remission (≤3.3), Clinical Disease Activity Index (CDAI ) remission (≤2.8), Boolean remission, and Disease Activity Score in 28 joints using the C‐reactive protein level (<2.6) were assessed. Results: Overall, 100 of 225 patients (44.4%) had high baseline MRI inflammation. In patients with high baseline MRI inflammation, a significantly greater proportion achieved remission at 12 months with abatacept plus MTX versus MTX across SDAI (45.1% versus 16.3%; P = 0.0022), CDAI (47.1% versus 20.4%; P = 0.0065), and Boolean indices (39.2% versus 16.3%; P = 0.0156). In patients with low baseline MRI inflammation, remission rates were not significantly different with abatacept plus MTX versus MTX (SDAI : 39.7% versus 32.3%; P = 0.4961). Conclusion: In seropositive, MTX ‐naive patients with early RA and presence of objectively measured high inflammation by MRI , indicating poor prognosis, remission rates were higher with abatacept plus MTX treatment versus MTX