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Boeters, D.M. 2020

Early identification and resolution of rheumatoid arthritis

Doctoral Thesis

open access

overzicht van verschillende voorspellers voor het ontwikkelen van RA binnen patiënten met artralgie

rol van nieuwe autoantistoffen en MRI in vroege diagnostiek RA

onderzoek naar behalen van DMARD...

overzicht van verschillende voorspellers voor het ontwikkelen van RA binnen patiënten met artralgie

rol van nieuwe autoantistoffen en MRI in vroege diagnostiek RA

onderzoek naar behalen van DMARD-vrije remissie: voorkomen van immunologische remissie en identificatie van subgroep van RA-patiënten met verhoogde kans op remissie

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Dakkak, Y.J.; Boer, A.C.; Boeters, D.M.; Niemantsverdriet, E.; Reijnierse, M.; Helm-van Mil, A.H.M. van der 2020

The relation between physical joint examination and MRI-depicted inflammation of metatarsophalangeal joints in early arthritis

Article / Letter to editor

open access

Background The relationship between physical joint examination (PE) and MRI-detected inflammation in early inflammatory arthritis has mostly been studied in the hands. Physical examination of MTP... Show moreBackground The relationship between physical joint examination (PE) and MRI-detected inflammation in early inflammatory arthritis has mostly been studied in the hands. Physical examination of MTP joints is considered difficult, and for these joints, this relationship is unknown. Therefore, we studied the concordance of PE with MRI inflammation in MTP joints. Metacarpophalangeal (MCP) joints were included for comparison. Methods One thousand seven hundred fifty-nine MTP(2-5) and 1750 MCP(2-5) joints of 441 consecutive patients with early arthritis underwent PE (for joint swelling) and MRI, all evaluated by two assessors. MRI was scored for synovitis, tenosynovitis, and osteitis (summed MRI inflammation). Synovial intermetatarsal bursae may enlarge upon inflammation and become palpable and were therefore also assessed. Analyses (frequencies, GEE) were performed on joint level. Results PE and MRI were concordant in 79% of MTP joints. Of 1606 non-swollen MTP joints, 83% showed no MRI inflammation and 17% showed subclinical MRI inflammation. Of 153 swollen MTP joints, 48% had MRI inflammation and 52% (79 MTP joints) did not. Of these 79 swollen MTP joints without MRI inflammation, 31 showed intermetatarsal bursitis and 48 joints had none of these MRI abnormalities (this concerned 31% of swollen MTP joints). MTP swelling was statistically independently associated with tenosynovitis (OR 2.21, 95% CI 1.1-4.3) and intermetatarsal bursitis (OR 2.91, 95% CI 1.8-4.8). MTP joints showed subclinical inflammation less often than MCP joints (17% vs. 34%, P < 0.001). Swollen MTP joints showed MRI inflammation less often than swollen MCP joints (48% vs. 88%, P < 0.001). Conclusions The absence of swelling of MTP joints in early arthritis is mostly accompanied by the absence of MRI-detected inflammation. Swollen MTP joints are, in addition to synovitis, also explained by tenosynovitis and intermetatarsal bursitis and partly unexplained by MRI. Their clinical relevance must be determined in longitudinal studies. Show less

Brinck, R.M. ten; Boeters, D.M.; Steenbergen, H.W. van; Helm-van Mil, A.H.M. van der 2020

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

Article / Letter to editor

open access

Introduction Arthralgia and MRI-detected subclinical inflammation can precede the development of clinically evident rheumatoid arthritis (RA). However, part of the patients presenting with... Show moreIntroduction 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. Show less

Matthijssen, X.M.E.; Wouters, F.; Boeters, D.M.; Boer, A.C.; Dakkak, Y.J.; Niemantsverdriet, E.; Helm-van Mil, A.H.M. van der 2019

A search to the target tissue in which RA-specific inflammation starts: a detailed MRI study to improve identification of RA-specific features in the phase of clinically suspect arthralgia

Article / Letter to editor

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Boeters, D.M.; Burgers, L.E.; Sasso, E.H.; Huizinga, T.W.J.; Helm-van Mil, A.H.M. van der 2019

ACPA-negative RA consists of subgroups: patients with high likelihood of achieving sustained DMARD-free remission can be identified by serological markers at disease presentation

Article / Letter to editor

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Dakkak, Y.J.; Boeters, D.M.; Boer, A.C.; Reijnierse, M.; Helm-van Mil, A.H.M. van der 2019

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

Article / Letter to editor

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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... Show moreMRI-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.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 ae 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.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.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. Show less

Ohrndorf, S.; Boer, A.C.; Boeters, D.M.; Brinck, R.M. ten; Burmester, G.R.; Kortekaas, M.C.; Helm-van Mil, A.H.M. van der 2019

Do musculoskeletal ultrasound and magnetic resonance imaging identify synovitis and tenosynovitis at the same joints and tendons? A comparative study in early inflammatory arthritis and clinically suspect arthralgia

Article / Letter to editor

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Boeters, D.M.; Trouw, L.A.; Helm-Van Mil, A.H.M. van der; Steenbergen, H.W. van 2018

Does information on novel identified autoantibodies contribute to predicting the progression from undifferentiated arthritis to rheumatoid arthritis: a study on anti-CarP antibodies as an example

Article / Letter to editor

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Background: The presence of autoantibodies is considered an important characteristic of rheumatoid arthritis (RA); therefore, both anticitrullinated protein antibodies (ACPA) and rheumatoid factor ... Show moreBackground: The presence of autoantibodies is considered an important characteristic of rheumatoid arthritis (RA); therefore, both anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are included in the 2010 classification criteria for rheumatoid arthritis (RA). However, a considerable number of RA patients lack both these autoantibodies. Recently, several novel autoantibodies have been identified but their value for the classification of RA patients is unclear. Therefore, we studied the value of novel autoantibodies using the presence of anticarbamylated protein (anti-CarP) antibodies as an example for predicting RA development in patients with undifferentiated arthritis (UA).Methods: There were 1352 UA patients included in the Leiden Early Arthritis Clinic (EAC) cohort according to the 1987 criteria. When the 2010 criteria were used, there were 838 UA patients. Of these, we evaluated whether they fulfilled the 1987 or 2010 criteria after 1 year, respectively. Logistic regression analyses were performed with RA as outcome and ACPA, RF, and anti-CarP antibodies as predictors. Analyses were repeated after stratification for ACPA and RF.Results: Thirty-three percent of the 1987-UA patients and 6% of the 2010-UA patients progressed to RA during the first year of follow-up. For the 1987-UA patients, anti-CarP antibodies were associated with progression to RA, an association which remained when a correction was made for the presence of ACPA and RF (odds ratio (OR) 1.7, 95% confidence interval (CI) 1.2-2.4). After stratification for ACPA and RF, anti-CarP antibodies were associated with progression to RA only for ACPA- and RF-negative patients (OR 2.1, 95% CI 1.3-3.7). For the 2010-UA patients, anti-CarP antibodies were associated with progression to RA; however, they were not when a correction was made for the presence of ACPA and RF (OR 0.8, 95% CI 0.3-2.1).Conclusions: Our finding that anti-CarP antibodies have no additional value when RA is defined according to the 2010 criteria might be inherent to the composition of the 2010 criteria and therefore might also apply to other novel autoantibodies. Potentially it would be interesting to evaluate other, non-autoantibody biomarkers. Show less

Boeters, D.M.; Trouw, L.A.; Helm-Van Mil, A.H.M. van der; Steenbergen, H.W. van 2018

Does information on novel identified autoantibodies contribute to predicting the progression from undifferentiated arthritis to rheumatoid arthritis: a study on anti-CarP antibodies as an example

Article / Letter to editor

open access

Burgers, L.E.; Boeters, D.M.; Reijnierse, M.; Helm-van Mil, A.H.M. van der 2018

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

Article / Letter to editor

open access

Boeters, D.M.; Gaujoux-Viala, C.; Constantin, A.; Helm-van Mil, A.H.M. van der 2017

The 2010 ACR/EULAR criteria are not sufficiently accurate in the early identification of autoantibody-negative rheumatoid arthritis: Results from the Leiden-EAC and ESPOIR cohorts

Article / Letter to editor

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Boeters, D.M.; Mangnus, L.; Ajeganova, S.; Lindqvist, E.; Svensson, B.; Toes, R.E.M.; ... ; Helm-van Mil, A.H.M. van der 2017

The prevalence of ACPA is lower in rheumatoid arthritis patients with an older age of onset but the composition of the ACPA response appears identical

Article / Letter to editor

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Boeters, D.M.; Nieuwenhuis, W.P.; Verheul, M.K.; Newsum, E.C.; Reijnierse, M.; Toes, R.E.M.; ... ; Helm-van Mil, A.H.M. van der 2016

MRI-detected osteitis is not associated with the presence or level of ACPA alone, but with the combined presence of ACPA and RF

Article / Letter to editor

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