ObjectiveUS can detect subclinical joint-inflammation in patients with clinically suspect arthralgia (CSA), which is valuable as predictor for RA development. In most research protocols both hands... Show moreObjectiveUS can detect subclinical joint-inflammation in patients with clinically suspect arthralgia (CSA), which is valuable as predictor for RA development. In most research protocols both hands and forefeet are scanned, but it is unclear if US of the forefeet has additional value for predicting RA, especially since synovial hypertrophy in MTP-joints of healthy individuals is also common. To explore the possibility to omit scanning of the forefeet we determined if US of the forefeet is of additional predictive value for RA-development in CSA patients.MethodsCSA patients of two independent cohorts underwent US of the hands and forefeet. We analysed the association between RA-development and US-positivity for the full US-protocol, the full US-protocol with correction for gray scale (GS)-findings in the forefeet of healthy and the protocol without forefeet.ResultsIn total, 298 CSA patients were studied. In patients with a positive US, subclinical joint-inflammation was mostly present in the hands (90–86%). Only 10–14% of patients had subclinical joint-inflammation solely in the forefeet. US-positivity was associated with inflammatory arthritis development in both cohorts, with HRs 2.6 (95% CI 0.9–7.5) and 3.1 (95% CI 1.5–6.4) for the full protocol, 3.1 (95% CI 1.3–7.7) and 2.7 (95% CI 1.3–5.4) for the full US-protocol with correction, and 3.1 (95% CI 1.4–6.9) and 2.8 (95% CI 1.4–5.6) without the forefeet. AUROCs were equal across both cohorts.ConclusionThe forefeet can be omitted when US is used for the prediction of RA-development in CSA patients. This is due to the finding that subclinical joint-inflammation in the forefeet without concomitant inflammation in the hands is infrequent. Show less
Predicting the development of rheumatoid arthritis (RA) in an early stage through magnetic resonance imaging (MRI) can initiate timely treatment and improve long-term patient outcomes. Although... Show morePredicting the development of rheumatoid arthritis (RA) in an early stage through magnetic resonance imaging (MRI) can initiate timely treatment and improve long-term patient outcomes. Although manual prediction is time-consuming and requires expert knowledge, automatic RA prediction has not been fully investigated. While standard models fail to achieve acceptable performance, we present a consistency-based deep learning framework to classify and predict RA automatically and precisely, including an output-standardized model, customized self-supervised pretraining and a loss function that is based on label consistency between original and augmented inputs. For training and evaluation, we used a database, containing 5945 MRI scans of carpal, metacarpophalangeal (MCP), and metatarsophalangeal (MTP) joints, from 2151 subjects obtained over a period of ten years. Four (three classification- and one prediction-) tasks were defined to distinguish two patient groups (with recent-onset arthritis and clinically suspect arthralgia) from healthy controls and RA from other arthritis patients within the recent-onset arthritis group, and predict RA development in a period of two years within the clinically suspect arthralgia group. The proposed method was evaluated with the area under the receiver operating curve (AUROC) on a separate test set, achieving mean AUROCs of 83.6%, 83.3%, and 69.7% in the three classification tasks, and 67.8% in the prediction task. This proves the existence of early signs of RA in MRI and the potential of a consistency-based deep learning model to detect these early signs and predict RA Show less
Henkemans, S.V.J.S.; Vis, M.; Looijen, A.E.M.; Mil, A.H.M.V.; Jong, P.H.P. de 2024
Objective To compare clinical and patient-reported outcomes (PROs) over 5 years between patients with rheumatoid arthritis (RA) in sustained remission (sREM), sustained low disease activity (sLDA)... Show moreObjective To compare clinical and patient-reported outcomes (PROs) over 5 years between patients with rheumatoid arthritis (RA) in sustained remission (sREM), sustained low disease activity (sLDA) or active disease (AD) in the first year after diagnosis. Methods All patients with RA from the treatment in the Rotterdam Early Arthritis CoHort trial, a multicentre, stratified, single-blinded trial with a treat-to-target approach, aiming for LDA (Disease Activity Score (DAS) ≤2.4), were studied. Patients were categorised into: (1) sREM (mean DAS from 6 to 12 months 2.4) (n=59). Pain, fatigue, functional impairment, health-related quality of life (HRQoL), health status and productivity loss during 5 years were compared between groups. Radiographic progression (modified Total Sharp Score (mTSS)) was compared over 2 years. Results Patients in sLDA in the first year had worse PROs during follow-up, compared with patients in sREM: pain (0–10 Likert) was 0.90 units higher (95% CI 0.52 to 1.27), fatigue (Visual Analogue Scale) was 12.10 units higher (95% CI 7.27 to 16.92), functional impairment (Health Assessment Questionnaire— Disability Index) was 0.28 units higher (95% CI 0.17 to 0.39), physical HRQoL (36-item Short Form Health Survey (SF-36) Physical Component Summary score) was 4.42 units lower (95% CI −6.39 to –2.45), mental HRQoL (SF-36 Mental Component Summary score (MCS)) was 2.95 units lower (95% CI −4.83 to –1.07), health status (European Quality of life 5-Dimensions 3-Levels (EQ-5D-3L)) was 0.06 units lower (95% CI −0.09 to –0.03) and productivity loss (0%–100%) was 7.76% higher (95% CI 2.76 to 12.75). Differences between the AD and sREM group were even larger, except for the SF-36 MCS and EQ5D-3L. No differences in mTSS were found between groups. Conclusion Patients with RA who reach sREM in the first year have better HRQoL and function, and less pain, fatigue and productivity loss in the years thereafter, compared with patients with RA who are in sLDA or AD in the first year. Show less
Objectives To investigate whether there is a window of opportunity for psoriatic arthritis (PsA) patients and to assess which patient characteristics are associated with a longer diagnostic delay.... Show moreObjectives To investigate whether there is a window of opportunity for psoriatic arthritis (PsA) patients and to assess which patient characteristics are associated with a longer diagnostic delay. Methods All newly diagnosed, disease-modifying antirheumatic drug-naïve PsA patients who participated in the Dutch southwest Early PsA cohoRt and had ≥3 years of follow-up were studied. First, total delay was calculated as the time period between symptom onset and PsA diagnosis made by a rheumatologist and then split into patient and physician delays. The total delay was categorised into short (1 year). These groups were compared on clinical (Minimal Disease Activity (MDA) and Disease Activity index for PSoriatic Arthritis (DAPSA) remission) and patientreported outcomes during 3 years follow-up. Results 708 PsA patients were studied of whom 136 (19%), 237 (33%) and 335 (47%) had a short, intermediate and long total delay, respectively. Patient delay was 1.0month and physician delay was 4.5 months. Patients with a short delay were more likely to achieve MDA (OR 2.55, p=0.003) and DAPSA remission (OR 2.35,p=0.004) compared with PsA patients with a long delay. Patientreported outcomes showed numerical but non-significant differences between the short and long delay groups. Female patients and those presenting with enthesitis, chronic back pain or normal C-reactive protein (CRP) had a longer delay. Conclusions In PsA, referral and diagnosis within 1 year is associated with better clinical outcomes, suggesting the presence of a window of opportunity. The most gain in referral could be obtained in physician delay and in females, patients with enthesitis, chronic back pain or normal CRP Show less
BackgroundObese RA patients have higher disease activity scores (DAS). Previous research showed that obese RA patients have higher tender joint count (TJC) and VAS general health. However, it... Show moreBackgroundObese RA patients have higher disease activity scores (DAS). Previous research showed that obese RA patients have higher tender joint count (TJC) and VAS general health. However, it remains unclear whether DAS components measuring local and systemic inflammation (swollen joint count (SJC), CRP) are increased and if this is present in the total RA population or confined to an ACPA subgroup. As ACPA is suggested to enhance inflammatory responses, we hypothesized that the association of obesity with SJC and CRP is present especially in ACPA-positive RA. We therefore studied associations of obesity with courses of DAS components in ACPA subgroups.MethodsWe studied 649 RA patients (291 ACPA-positive), included in the Leiden Early Arthritis Clinic. Five-year courses of DAS44 and DAS44 components (SJC-44, TJC-53, CRP, VAS (0-100)) were compared between RA patients with normal weight (BMI 18.5-24.9), overweight (25.0-29.9), and obesity (>= 30.0), stratified for ACPA. Linear/Poisson mixed models with a knot at 4 months were used.ResultsObese RA patients had + 0.32 higher DAS compared to normal weight during the 5-year follow-up. In ACPA-positive RA, obese patients had + 0.43 (95% CI: 0.22, 0.64) higher DAS, whereas in ACPA-negative RA, this difference was smaller and not statistically significant: + 0.19 (95% CI: - 0.01, 0.38). In ACPA-positive RA, all DAS components were significantly higher in obese patients compared to normal weight: SJC + 60% (IRR1.60; 95% CI: 1.18, 2.16), CRP + 3.7 mg/L (95% CI:0.95, 6.53), TJC + 55% (IRR1.55; 95% CI:1.15, 2.10), and VAS + 9 (95% CI: 4.0, 14.2). ACPA-negative obese RA patients tended to have higher TJC (IRR1.22; 95% CI: 0.96, 1.55) and VAS (beta 4.3; 95% CI: - 0.4, 9.0), while SJC (IRR1.07; 95% CI:0.85, 1.33) and CRP (beta 0.24; 95% CI: - 1.29, 3.32) were unaffected.ConclusionThe association of obesity with a worse DAS course is mainly present in ACPA-positive RA; especially SJC and CRP levels remain higher in ACPA-positive RA patients with obesity but not ACPA-negative RA patients. This is the first demonstration that obesity influences the disease course of ACPA-positive and ACPA-negative RA differently. Show less
ObjectivesThe severity of fatigue in RA has improved very little in recent decades, leaving a large unmet need. Fortunately, not all RA patients suffer from persistent fatigue, but the subgroup of... Show moreObjectivesThe severity of fatigue in RA has improved very little in recent decades, leaving a large unmet need. Fortunately, not all RA patients suffer from persistent fatigue, but the subgroup of patients who suffer the most is insufficiently recognizable at diagnosis. As disease activity is partly coupled to fatigue, DAS components may associate with the course of fatigue. We aimed to identify those RA patients who remain fatigued by studying DAS components at diagnosis in relation to the course of fatigue over a 5-year follow-up period in two independent early RA cohorts.MethodsIn all, 1560 consecutive RA patients included in the Leiden Early Arthritis Cohort and 415 RA patients included in the tREACH trial were studied. Swollen joint count, tender joint count, ESR and Patient Global Assessment (PGA) [on a Visual Analogue Scale (VAS)] were studied in relation to fatigue (VAS, 0–100 mm) over a period of 5 years, using linear mixed models.ResultsHigher tender joint count and higher PGA at diagnosis were associated with a more severe course of fatigue. Furthermore, patients with mono- or oligo-arthritis at diagnosis remained more fatigued. The swollen joint count, in contrast, showed an inverse association. An investigation of combinations of the aforementioned characteristics revealed that patients presenting with mono- or oligo-arthritis and PGA ≥ 50 remained the most fatigued over time (+20 mm vs polyarthritis with PGA < 50), while the DAS course over time did not differ. This subgroup comprised 14% of the early RA population. Data from the tREACH trial showed similar findings.ConclusionThe RA patients who remain the most fatigued were those characterized by mono- or oligo-arthritis and high PGA (VAS ≥ 50) at diagnosis. This understanding may enable early-intervention with non-pharmacological approaches in dedicated patient groups. Show less
Background Inflammation around the tendons of interosseous muscles of the hand (interosseous tendon inflammation) was recently observed with MRI for the first time in patients with rheumatoid... Show moreBackground Inflammation around the tendons of interosseous muscles of the hand (interosseous tendon inflammation) was recently observed with MRI for the first time in patients with rheumatoid arthritis and in at-risk individuals with detectable anti-citrullinated protein antibodies, generating the hypothesis that interosseous tendon inflammation precedes clinical arthritis. To better understand the role of interosseous tendon inflammation during the development of rheumatoid arthritis, we studied the frequency of interosseous tendon inflammation in healthy individuals and in those with arthralgia that was suspected of progressing to rheumatoid arthritis (ie, clinically suspect arthralgia) and the association of interosseous tendon inflammation with other symptoms of inflamed joint tissues and with clinical arthritis development.Methods Adult (age >= 18 years) patients who presented with clinically suspect arthralgia and symptom-free (control) individuals underwent contrast-enhanced hand MRI. MRIs were evaluated for interosseous tendon inflammation on the radial and ulnar sides of the second to fifth metacarpophalangeal joints, and for synovitis, tenosynovitis, and osteitis using the rheumatoid arthritis MRI scoring system. Patients with clinically suspect arthralgia were followed up for clinical arthritis development. The presence of local tenosynovium was examined using immunohistochemistry for anti-CD55 and anti-CD68 on tissue from the hands of three embalmed bodies donated for scientific research. The primary outcome for the cross-sectional part of the study was the presence of interosseous tendon inflammation on MRI. The primary outcome for the longitudinal part of the study was development of clinical arthritis.Findings Between April 3, 2012, and May 20, 2020, 667 patients with clinically suspect arthralgia (mean age 44 years [SD 13], 504 [76%] were women and 163 [24%] were men) underwent contrast-enhanced hand MRI. Between Nov 1, 2013, and Nov 30, 2014, 193 symptom-free controls were recruited (mean age 50 years [SD 16], 136 [70%] were women and 57 [30%] were men). Two (1%) of 193 symptom-free controls had interosseous tendon inflammation. Immunohistochemistry of cadaveric hand tissues showed no tenosynovium surrounding interosseous tendons. At inclusion, 67 (10%) of 667 patients with clinically suspect arthralgia had interosseous tendon inflammation (p<00001 vs symptom-free controls). Interosseous tendon inflammation occurred more frequently if synovitis (odds ratio [OR] 22 [95% CI 12-42]), or tenosynovitis (OR 97 [55-170]), was present at metacarpophalangeal joints. A three-dimensional MRI reconstruction suggested confluency of interosseous tendon inflammation with metacarpophalangeal-flexor-tenosynovitis. 91 (16%) of 558 patients with clinically suspect arthralgia developed clinical arthritis during follow-up (median total follow-up 253 months [95% CI 251-255]). Patients with clinically suspect arthralgia with interosseous tendon inflammation had a higher risk of developing clinical arthritis (hazard ratio [HR] 45 [28-72]), which was attenuated but still significant after adjusting for concomitant synovitis, tenosynovitis, or osteitis (HR 17 [102-28]).Interpretation Interosseous tendon inflammation is almost absent in symptom-free individuals but occurs in people with clinically suspect arthralgia, in whom it correlates with symptoms and is associated with the development of clinical arthritis. The absence of local tenosynovium suggests that interosseous tendon inflammation arises from expanding local subclinical inflammation in the pre-arthritis phase of rheumatoid arthritis. Show less
Objectives: Autoantibody responses increase years before the onset of inflammatory arthritis (IA) and are stable during transitioning from clinically suspect arthralgia (CSA) to IA. Cytokine and... Show moreObjectives: Autoantibody responses increase years before the onset of inflammatory arthritis (IA) and are stable during transitioning from clinically suspect arthralgia (CSA) to IA. Cytokine and chemokine levels also increase years before IA onset. However, the course in the at-risk stage of CSA during progression to disease or non-progression is unknown. To increase the understanding of processes mediating disease development, we studied the course of cytokine, chemokine and related receptors gene expression in CSA patients during progression to IA and in CSA patients who ultimately did not develop IA. Methods: Whole-blood RNA expression of 37 inflammatory cytokines, chemokines and related receptors was determined by dual-colour reverse transcription multiplex ligation-dependent probe amplification in paired samples of CSA patients at CSA onset and either at IA development or after 24 months without IA development. ACPA-positive and ACPA-negative CSA patients developing IA were compared at CSA onset and during progression to IA. Generalised estimating equations tested changes over time. A false discovery rate approach was applied. Results: None of the cytokine/chemokine genes significantly changed in expression between CSA onset and IA development. In CSA patients without IA development, G-CSF expression decreased (P = 0.001), whereas CCR6 and TNIP1 expression increased (P < 0.001 and P = 0.002, respectively) over a 2 year period. Expression levels in ACPA-positive and ACPA-negative CSA patients who developed IA were similar. Conclusion: Whole-blood gene expression of assessed cytokines, chemokines and related receptors did not change significantly from CSA to IA development. This suggests that changes in expression of these molecules may not be related to the final process of developing chronicity and may have occurred preceding CSA onset. Changes in gene expression in CSA patients without IA development may provide clues for processes related to resolution. Show less
Background: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive... Show moreBackground: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive joint destruction if inadequately treated. Standard care consists primarily of disease-modifying anti-rheumatic drugs (DMARDs), often supported by systemic corticosteroids or intra-articular corticosteroid injections (IACSI). IACSI, despite their use worldwide, show poor response in a substantial group of patients. Arthroscopic synovectomy of the wrist is the surgical removal of synovitis with the goal to relieve pain and improve wrist function. The primary objective of this study is to evaluate wrist function following arthroscopic synovectomy compared to IACSI in therapy-resistant patients with rheumatoid or psoriatic arthritis. Secondary objectives include radiologic progress, disease activity, health-related quality of life, work participation and cost-effectiveness during a 1-year follow-up. Methods: This protocol describes a prospective, randomized controlled trial. RA and PsA patients are eligible with prominent wrist synovitis objectified by a rheumatologist, not responding to at least 3 months of conventional DMARDs and naive to biological DMARDs. For 90% power, an expected loss to follow-up of 5%, an expected difference in mean Patient-Rated Wrist Evaluation score (PRWE, range 0-100) of 11 and alpha = 0.05, a total sample size of 80 patients will be sufficient to detect an effect size. Patients are randomized in a 1:1 ratio for arthroscopic synovectomy with deposition of corticosteroids or for IACSI. Removed synovial tissue will be stored for an ancillary study on disease profiling. The primary outcome is wrist function, measured with the PRWE score after 3 months. Secondary outcomes include wrist mobility and grip strength, pain scores, DAS28, EQ-5D-5L, disease progression on ultrasound and radiographs, complications and secondary treatment. Additionally, a cost-effectiveness analysis will be performed, based on healthcare costs (iMCQ questionnaire) and productivity loss (iPCQ questionnaire). Follow-up will be scheduled at 3, 6 and 12 months. Patient burden is minimized by combining study visits with regular follow-ups. Discussion: Persistent wrist arthritis continues to be a problem for patients with rheumatic joint disease leading to disability. This is the first randomized controlled trial to evaluate the effect, safety and feasibility of arthroscopic synovectomy of the wrist in these patients compared to IACSI.Trial registration: Dutch trial registry (CCMO), NL74744.100.20. Registered on 30 November 2020.ClinicalTrials.gov NCT04755127. Registered after the start of inclusion on 15 February 2021. Show less
BackgroundRheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive joint... Show moreBackgroundRheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive joint destruction if inadequately treated. Standard care consists primarily of disease-modifying anti-rheumatic drugs (DMARDs), often supported by systemic corticosteroids or intra-articular corticosteroid injections (IACSI). IACSI, despite their use worldwide, show poor response in a substantial group of patients. Arthroscopic synovectomy of the wrist is the surgical removal of synovitis with the goal to relieve pain and improve wrist function. The primary objective of this study is to evaluate wrist function following arthroscopic synovectomy compared to IACSI in therapy-resistant patients with rheumatoid or psoriatic arthritis. Secondary objectives include radiologic progress, disease activity, health-related quality of life, work participation and cost-effectiveness during a 1-year follow-up.MethodsThis protocol describes a prospective, randomized controlled trial. RA and PsA patients are eligible with prominent wrist synovitis objectified by a rheumatologist, not responding to at least 3 months of conventional DMARDs and naïve to biological DMARDs. For 90% power, an expected loss to follow-up of 5%, an expected difference in mean Patient-Rated Wrist Evaluation score (PRWE, range 0–100) of 11 and α = 0.05, a total sample size of 80 patients will be sufficient to detect an effect size. Patients are randomized in a 1:1 ratio for arthroscopic synovectomy with deposition of corticosteroids or for IACSI. Removed synovial tissue will be stored for an ancillary study on disease profiling. The primary outcome is wrist function, measured with the PRWE score after 3 months. Secondary outcomes include wrist mobility and grip strength, pain scores, DAS28, EQ-5D-5L, disease progression on ultrasound and radiographs, complications and secondary treatment. Additionally, a cost-effectiveness analysis will be performed, based on healthcare costs (iMCQ questionnaire) and productivity loss (iPCQ questionnaire). Follow-up will be scheduled at 3, 6 and 12 months. Patient burden is minimized by combining study visits with regular follow-ups.DiscussionPersistent wrist arthritis continues to be a problem for patients with rheumatic joint disease leading to disability. This is the first randomized controlled trial to evaluate the effect, safety and feasibility of arthroscopic synovectomy of the wrist in these patients compared to IACSI. Show less
During the last decade, the outlook for patients with rheumatoid arthritis (RA) has improved greatly, especially for patients with autoantibody-positive RA. To further improve long-term disease... Show moreDuring the last decade, the outlook for patients with rheumatoid arthritis (RA) has improved greatly, especially for patients with autoantibody-positive RA. To further improve long-term disease outcomes, the field has turned to investigating the efficacy of treatment initiated in the pre-arthritic phase of RA, based on the adage "the sooner the better." In this review, the concept of prevention is evaluated and different risk stages are being examined for their pre-test risks of RA development. These risks affect the post-test risk of biomarkers used at these stages and, consequently, the accuracy with which the risk of RA can be estimated. Furthermore, through their effect on accurate risk stratification, these pre-test risks ultimately also associate with the likelihood of false-negative trial results (the so-called "clinicostatistical tragedy"). Outcome measures to assess preventive effects are evaluated and relate to either the occur-rence of disease itself or to the severity of risk factors for RA development. Results of recently completed prevention studies are discussed in the light of these theoretical considerations. The results vary, but clear prevention of RA has not been demonstrated. While some treatments (e.g. methotrexate) persistently reduced symptom severity, physical disability, and the severity of imaging joint inflammation, other treatments were not reported to produce long-lasting effects (hydroxychloroquine, rituximab, atorvas-tatin). The review concludes with future perspectives regarding the design of new prevention studies and considerations and requirements before findings can be implemented in daily practice in individuals at risk of RA attending rheumatology practices.(c) 2023 L'Auteur(s). Publie par Elsevier Masson SAS au nom de Societe franc,aise de rhumatologie. Cet article est publie en Open Access sous licence CC BY (http://creativecommons.org/licenses/by/4.0/). Show less
Background: Clinically suspect arthralgia (CSA) is characterised by arthralgia of small joints and considered a risk stage for development of rheumatoid arthritis (RA). However, it remains unknown... Show moreBackground: Clinically suspect arthralgia (CSA) is characterised by arthralgia of small joints and considered a risk stage for development of rheumatoid arthritis (RA). However, it remains unknown if the function of the hands is already affected and what mechanisms underlie impaired hand-function in CSA.Methods: We studied various measures of hand function in two CSA populations. CSA patients in the TREAT EARLIER-trial (n=236) were evaluated at baseline for: grip strength on a dynamometer (GS), patient-reported difficulties in the grip domain of the Health Assessment Questionnaire (HAQ) questionnaire and incomplete fist closure at physical examination. Findings were validated in an independent CSA cohort (n=600) where hand function was measured as: GS evaluated by squeezing the examiner's fingers, grip domain of the HAQ questionnaire and fist closure. Contrast-enhanced MRI of the hands measured synovitis, tenosynovitis and bone marrow oedema (summed as subclinical inflammation) in both cohorts. Results: GS (on a dynamometer) was reduced in 75% compared with reference values in healthy controls, 60% reported grip difficulties and 13% had incomplete fist closure. Reduced GS was associated with subclinical inflammation (-0.38 kg/point inflammation, 95% CI -0.68 to -0.08). Studying separate MRI features, GS reduction was independently associated with tenosynovitis, decreasing with -2.63 kg (95% CI -2.26 to -0.33)/point tenosynovitis (range observed tenosynovitis scores: 0-20). Similar relations with tenosynovitis were seen for patient-reported grip difficulties (OR 1.12/point, 95% CI 1.07 to 1.42) and incomplete fist closure (OR 1.36/point, 95% CI 1.03 to 1.79). In the validation cohort, 36% had decreased examiner-assessed GS, 51% reported grip difficulties and 14% incomplete fist closure: all were associated with tenosynovitis. Decreased dynamometer-measured GS was most sensitive for detecting tenosynovitis (75%), while incomplete fist closure was most specific (88%-90%). Conclusion: Hand function is already often affected before RA development. These limitations are related to subclinical inflammation and tenosynovitis in particular. Show less
Maurits, M.P.; Wouters, F.; Niemantsverdriet, E.; Huizinga, T.W.J.; Akker, E.B. van den; Cessie, S. le; ... ; Knevel, R. 2022
Objective. To investigate whether established genetic predictors for rheumatoid arthritis (RA) differentiate healthy controls, patients with clinically suspect arthralgia (CSA), and RA patients... Show moreObjective. To investigate whether established genetic predictors for rheumatoid arthritis (RA) differentiate healthy controls, patients with clinically suspect arthralgia (CSA), and RA patients.Methods. Using analyses of variance, chi-square tests, and mean risk difference analyses, we investigated the association of an RA polygenic risk score (PRS) and HLA shared epitope (HLA-SE) with all participant groups, both unstratified and stratified for anti-citrullinated protein antibody (ACPA) status. We used 3 separate data sets sampled from the same Dutch population (1,015 healthy controls, 479 CSA patients, and 1,146 early classified RA patients). CSA patients were assessed for conversion to inflammatory arthritis over a period of 2 years, after which they were classified as either CSA converters (n = 84) or CSA nonconverters (n = 395).Results. The PRS was increased in RA patients (mean +/- SD PRS 1.31 +/- 0.96) compared to the complete CSA group (1.07 +/- 0.94) and compared to CSA converters (1.12 +/- 0.94). In ACPA- strata, PRS distributions differed strongly when comparing the complete CSA group (mean +/- SD PRS 1.05 +/- 0.94) and CSA converters (0.97 +/- 0.87) to RA patients (1.20 +/- 0.94), while in the ACPA+ strata, the complete CSA group (1.25 +/- 0.99) differed clearly from healthy controls (1.05 +/- 0.94) and RA patients (1.41 +/- 0.96). HLA-SE was more prevalent in the RA group (prevalence 0.64) than the complete CSA group (0.45), with small differences between RA patients and CSA converters (0.64 versus 0.60) and larger differences between CSA converters and CSA nonconverters (0.60 versus 0.42). HLA-SE prevalence differed more strongly within the ACPA+ strata as follows: healthy controls (prevalence 0.43), CSA nonconverters (0.48), complete CSA group (0.59), CSA converters (0.66), and RA patients (0.79).Conclusion. We observed that genetic predisposition increased across pre-RA participant groups. The RA PRS differed in early classified RA and inflammatory pre-disease stages, regardless of ACPA stratification. HLA-SE prevalence differed between arthritis patients, particularly ACPA+ patients, and healthy controls. Genetics seem to fulfill different etiologic roles. Show less
Maurits, M.P.; Wouters, F.; Niemantsverdriet, E.; Huizinga, T.W.J.; Akker, E.B. van den; Cessie, S. le; ... ; Knevel, R. 2022
ObjectiveTo investigate whether established genetic predictors for rheumatoid arthritis (RA) differentiate healthy controls, patients with clinically suspect arthralgia (CSA), and RA patients... Show moreObjectiveTo investigate whether established genetic predictors for rheumatoid arthritis (RA) differentiate healthy controls, patients with clinically suspect arthralgia (CSA), and RA patients.MethodsUsing analyses of variance, chi-square tests, and mean risk difference analyses, we investigated the association of an RA polygenic risk score (PRS) and HLA shared epitope (HLA-SE) with all participant groups, both unstratified and stratified for anti–citrullinated protein antibody (ACPA) status. We used 3 separate data sets sampled from the same Dutch population (1,015 healthy controls, 479 CSA patients, and 1,146 early classified RA patients). CSA patients were assessed for conversion to inflammatory arthritis over a period of 2 years, after which they were classified as either CSA converters (n = 84) or CSA nonconverters (n = 395).ResultsThe PRS was increased in RA patients (mean ± SD PRS 1.31 ± 0.96) compared to the complete CSA group (1.07 ± 0.94) and compared to CSA converters (1.12 ± 0.94). In ACPA– strata, PRS distributions differed strongly when comparing the complete CSA group (mean ± SD PRS 1.05 ± 0.94) and CSA converters (0.97 ± 0.87) to RA patients (1.20 ± 0.94), while in the ACPA+ strata, the complete CSA group (1.25 ± 0.99) differed clearly from healthy controls (1.05 ± 0.94) and RA patients (1.41 ± 0.96). HLA-SE was more prevalent in the RA group (prevalence 0.64) than the complete CSA group (0.45), with small differences between RA patients and CSA converters (0.64 versus 0.60) and larger differences between CSA converters and CSA nonconverters (0.60 versus 0.42). HLA-SE prevalence differed more strongly within the ACPA+ strata as follows: healthy controls (prevalence 0.43), CSA nonconverters (0.48), complete CSA group (0.59), CSA converters (0.66), and RA patients (0.79).ConclusionWe observed that genetic predisposition increased across pre-RA participant groups. The RA PRS differed in early classified RA and inflammatory pre-disease stages, regardless of ACPA stratification. HLA-SE prevalence differed between arthritis patients, particularly ACPA+ patients, and healthy controls. Genetics seem to fulfill different etiologic roles. Show less
Objective: To compare patient-reported outcomes (PROs) from the first year to the third year between patients with psoriatic arthritis (PsA) who achieved minimal disease activity (MDA) in the first... Show moreObjective: To compare patient-reported outcomes (PROs) from the first year to the third year between patients with psoriatic arthritis (PsA) who achieved minimal disease activity (MDA) in the first year after diagnosis and those who did not. Methods:Consecutive, newly diagnosed, patients with DMARD naive PsA with oligoarthritis or polyarthritis were selected from the Dutch southwest Early PsA cohoRt. Patients were categorised in three groups: (1) Patients who were in MDA at both 9 months and 12 months after diagnosis (sustained MDA); (2) Patients who achieved MDA in the first year but in whom it was not sustained at both 9 months and 12 months (non-sustained MDA); (3) Patients who did not achieve MDA in the first year (no MDA). PROs were compared between groups from the first year to the third year after diagnosis using a linear mixed model. Results: 240 patients were selected; 104 (43%) were classified as sustained MDA, 60 (25%) as non-sustained MDA and 76 (32%) as no MDA. Patients who did not achieve MDA in the first year experienced remarkably lower PROs during follow-up, compared with the sustained MDA group: health status (European Quality of life 5-Dimensions 5-Levels) was 0.23 units lower (95% CI -0.28 to -0.18), functional impairment (Health Assessment Questionnaire-Disability Index) was 0.81 units higher (95% CI 0.70 to 0.92), pain (Visual Analogue Scale) was 35.38 mm higher (95% CI 30.57 to 40.18), fatigue (Bristol Rheumatoid Arthritis Fatigue-Multidimensional Questionnaire) was 17.88 units higher (95% CI 14.60 to 21.16), and anxiety and depression (Hospital Anxiety and Depression Scale) were, respectively, 3.26 units (95% CI 2.25 to 4.27) and 4.04 units higher (95% CI 3.10 to 4.99). Conclusion: Failure to achieve MDA in the first year after PsA diagnosis was associated with worse PROs that persisted over the years. Show less
Niemantsverdriet, E.; Akker, E.B. van den; Boeters, D.M.; Eeden, S.J.F. van den; Geluk, A.; Mil, A.H.M.V. 2020
