Early Arthritis Research Articles

Most unicompartmental knee replacement revisions could be avoided: a radiographic evaluation of revised Oxford knees in the National Joint Registry

PurposeThe purpose of this study was to understand why the revision rate of unicompartmental knee replacement (UKR) in the National Joint Registry (NJR) is so high. Using radiographs, the appropriateness of patient selection for primary surgery, surgical technique, and indications for revision were determined. In addition, the alignment of the radiographs was assessed.MethodsOxford UKR registered with the NJR between 2006 and 2010 and subsequently revised were identified by the NJR. A blinded review was undertaken of pre-primary, post-primary, and pre-revision anteroposterior and lateral radiographs of a sample of 107 cases from multiple centres.ResultsThe recommended indications were satisfied in 70%, with 29% not demonstrating bone-on-bone arthritis. Major technical errors, likely leading to revision, were seen in 6%. Pre-revision radiographs were malaligned and, therefore, difficult to interpret in 53%. No reason for revision was seen in 67%. Reasons for revision included lateral compartment arthritis (10%), tibial loosening (7%), bearing dislocation (7%), infection (6%), femoral loosening (3%), and peri-prosthetic fracture (2%, one femoral, one tibial).ConclusionsOnly 20% of the revised UKR were implanted for the recommended indications, using appropriate surgical technique and had a mechanical problem necessitating revision. One-third of primary surgeries were undertaken in patients with early arthritis, which is contraindicated. Two-thirds were presumably revised for unexplained pain, which is not advised as it tends not to help the pain. This study suggests that variable and inappropriate indications for primary and revision surgery are responsible for the high rates of revision seen in registries.Level of evidenceIII, Therapeutic study.

Factors Predicting Early Failure of Etanercept in Rheumatoid Arthritis: An Analysis From the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis) Registry.

This study aims to investigate the factors associated with early discontinuation (within one year) of etanercept (ETA) in rheumatoid arthritis (RA) patients who began ETA as first biologic disease-modifying antirheumatic drug (bDMARD) and who were entered into the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis; GISEA) registry. This registry-based cohort study included 477 RA patients (95 males, 382 females; median age 53 years; range 18 to 83 years) who began ETA as first bDMARD. Patient demographics, disease features and drugs were re-evaluated after 12 months. Baseline predictors of ETA discontinuation were estimated by univariate and multivariate analyses using Cox regression model. Seventy patients (14.7%) discontinued ETA during the first year (for inefficacy in 55.8%, adverse events in 28.6%, and other reasons in 6.5%). Concurrent conventional synthetic DMARDs (csDMARDs) were reported in 54.3% of patients, mainly methotrexate (MTX), while 52.4% of subjects took low doses of glucocorticoids. Patients stopping ETA more frequently showed one or more comorbidities, mainly cardiovascular diseases (28.6% vs. 15.7% in patients stopping and continuing ETA, respectively, p=0.009). The presence of comorbidities and a combination therapy with csDMARDs other than MTX were independent factors associated with early discontinuation of ETA at multivariate Cox analysis. Although ETA demonstrated a high persistence in biologic-naïve RA patients, about 15% of patients discontinued the treatment within 12 months. The presence of comorbidities and a combination therapy with csDMARDs other than MTX were the main factors for an early withdrawal of the drug.

Altered T cell plasticity favours Th17 cells in early arthritis.

The predominance of differentiated Th17 cells has been implied as a key driver of autoimmune arthritis, including early RA. Because accumulating evidence suggests that Th cell differentiation is a plastic process, we investigated plasticity and underlying molecular mechanisms to address the shift towards the Th17 phenotype in early RA. A cohort of 61 patients with early, active, untreated RA and 45 age- and sex-matched healthy controls were studied. Viable in vitro- and in vivo-generated Th1, Th2 and Th17 cells were FACS-sorted and transdifferentiated under Th1-, Th2- or Th17-inducing conditions. The cytokine Th profile of the transdifferentiated cells was assessed by flow cytometry. Th cell-associated cytokine and transcription factor gene loci were analysed by chromatin immunoprecipitation assay and their expression by quantitative real-time PCR. In vitro-generated Th cells showed substantial plasticity, which was similar between RA and healthy controls, whereas in vivo-derived Th1 and Th2 cells from RA patients demonstrated an enhanced plasticity towards IL-17-expressing phenotypes compared with healthy controls. Further, in vivo-generated Th17 cells from RA patients showed a resistance to transdifferentiate into Th1 or Th2 cells. The serum/glucocorticoid-regulated kinase 1-forkhead box protein O1-IL-23 receptor (SGK1-FOXO1-IL-23R) axis together with increased RORC expression was associated with the predominant Th17 phenotype in early RA. Our data indicate that in vivo-originated Th subsets are prone to Th17 cell transdifferentiation in early RA, while Th17 cells are resistant to changes in their phenotype. Together, the data imply that an altered plasticity contributes to the Th17 shift in early RA.

Prevalence and clinical significance of extra-articular manifestations at diagnosis in the ESPOIR cohort with recent-onset arthritis

ObjectivesThe aim of this study was to determine the prevalence and clinical significance of extra-articular manifestations (EAMs) at inclusion into a cohort of patients with recent-onset arthritis consistent with rheumatoid arthritis (RA). MethodsThe ESPOIR cohort included patients aged 18 to 70 years who had a definitive or probable diagnosis of RA. Symptoms consistent with EAMs were collected at baseline. We divided the patients into two groups, with vs. without baseline EAMs. We looked for associations linking the presence of EAMs at baseline to patient and disease characteristics at baseline and 5 years later, as well as to diagnostic certainty after 2 years. The analyses were adjusted for multiple comparisons using the Benjamini–Hochberg procedure to control the false discovery rate. ResultsOf 798 patients, 330 (41.4%) had at least one symptom consistent with EAM at baseline, with the most common being sicca syndrome (28.4%) and Raynaud's phenomenon (17.3%). The EAM+ group had a higher mean baseline DAS-28 value (5.3 ± 1.3 versus 5.0 ± 1.3; corrected p value = 0.005) compared to the EAM- group. The final diagnosis did not differ between the two groups. After 5 years, the EAM+ group had significantly higher values for the tender joint count (3.9 ± 6.4 versus 1.8 ± 3.3, corrected p value = 0.005) and swollen joint count (1.3 ± 2.8 versus 1.1 ± 2.3, corrected p value =0.0005) compared to the EAM- group. ConclusionEAMs, particularly sicca syndrome and Raynaud's phenomenon, are very common in patients with early arthritis consistent with RA. In this population, several parameters reflecting disease activity were higher among patients with EAMs, at baseline and after 5 years.

The P. gingivalis Autocitrullinome Is Not a Target for ACPA in Early Rheumatoid Arthritis

Rheumatoid arthritis (RA), a chronic inflammatory disease affecting primarily the joints, is frequently characterized by the presence of autoimmune anticitrullinated protein antibodies (ACPA) during preclinical stages of disease and accumulation of hypercitrullinated proteins in arthritic joints. A strong association has been reported between RA and periodontal disease, and Porphyromonas gingivalis, a known driver of periodontitis, has been proposed as the microbial link underlying this association. We recently demonstrated P. gingivalis–mediated gut barrier breakdown and exacerbation of joint inflammation during inflammatory arthritis. In the present study, we investigated another potential role for P. gingivalis in RA etiopathogenesis, based on the generation of ACPA through the activity of a unique P. gingivalis peptidylarginine deiminase (PPAD) produced by this bacterium, which is capable of protein citrullination. Using a novel P. gingivalis W50 PPAD mutant strain, incapable of protein citrullination, and serum from disease-modifying antirheumatic drug–naïve early arthritis patients, we assessed whether autocitrullinated proteins in the P. gingivalis proteome serve as cross-activation targets in the initiation of ACPA production. We found no evidence for patient antibody activity specific to autocitrullinated P. gingivalis proteins. Moreover, deletion of PPAD did not prevent P. gingivalis–mediated intestinal barrier breakdown and exacerbation of disease during inflammatory arthritis in a murine model. Together, these findings suggest that the enzymatic activity of PPAD is not a major virulence mechanism during early stages of inflammatory arthritis.

Mixed methods study of a new model of care for chronic disease: co-design and sustainable implementation of group consultations into clinical practice.

ObjectivesGroup consultations are used for chronic conditions, such as inflammatory arthritis, but evidence of efficacy for treatment to target or achieving tight control is lacking. Our aim was to establish whether group consultation is a sustainable, co-designed routine care option and to explore factors supporting spread.MethodsThe study used mixed methods, observational process/outcome data, plus qualitative exploration of enabling themes. It was set in two community hospitals, in 2008–19, with a third hospital from 2016, and was triangulated with primary care qualitative data. There was a total of 3363 arthritis patient attendances at 183 clinics during 2008–19. The early arthritis cohort comprised 46 patients, followed monthly until the treatment target was achieved, during 2016–19. Focus groups included 15 arthritis and 11 osteoporosis group attendees. Intervention was a 2 h group consultation, attended monthly for early/active disease and annually for stable disease. Measurements included attendance, DAS, satisfaction and enabling themes.ResultsThere was a mean number of 18.4 patients per clinic (n = 16, 2010–15; n = 18, 2016; n = 20, 2017; n = 23, 2018–19). Forty per cent (1161/2874) of patients with DAS data reached low disease activity (DAS < 3.2) or remission (DAS < 2.6). Forty-six early arthritis patients followed monthly until they achieved remission responded even better: 50% remission; and 89% low disease activity/remission by 6 months. Qualitative analysis derived five main enabling themes (efficiency, empathy, education, engagement and empowerment) and five promotors to translate these themes into practice (prioritization, personalization, participation, personality and pedagogy). Limitations included the prospectively collected observational data and pragmatic design susceptible to bias.ConclusionCo-designed group consultations can be sustainable, clinically effective and efficient for monthly review of early active disease and annual review of stable disease. Promoting factors may support effective training for chronic disease group consultations.

Editorial introductions

Editorial introductions

Tubercular arthritis presenting as osteonecrosis of the femoral head: A case report

A tuberculosis hip that presents as osteonecrosis of the femoral head is an extremely rare condition. There are no previous reports of this condition, and there is no consensus on the method of total hip arthroplasty for this group of patients. We present a case of a 72-year-old man who had clinical gradual hip pain in both hips for 1 year. He was diagnosed with post-collapsed osteonecrosis of the femoral head in both hips and was scheduled for total hip arthroplasty of the left hip. During his clinical follow-up, he suddenly experienced excruciating acute pain. Investigation to rule out infection was positive for only C-reactive proteins, but his synovial fluid work-up was negative. An intraoperative finding revealed that there was collapse of the femoral head with eroded acetabular cartilage and rice body–like synovitis. Total hip arthroplasty was performed, and the tissue was sent for diagnosis. Tissue acid-fast bacilli were positive, so the patient received anti-tuberculosis drugs for 9 months, with no recurrent infection. Tuberculosis arthritis presenting as osteonecrosis of the femoral head is a complex condition that is difficult to diagnose due to the radiographic pictures of femoral head collapse and arthritic change being similar in both diseases. Acute pain onset with rapid collapse of the femoral head should be a consideration or suspect for this infectious condition. Hence, investigation to rule out infection is important. Anti-tuberculosis drugs are the standard treatment for early or advanced arthritis, and one-stage or two-stage total hip arthroplasty is the choice of treatment for advanced arthritis.

An analysis of surgical management of acetabular fractures

With increase in number of high-speed road traffic accidents the incidence of acetabular fracture is increasing. Historically satisfactory results after non operative treatment of acetabular fractures were obtained only in a minority of cases (13-30%). Non operative treatment options include traction and early mobilization with progressive weight bearing. Unsuccessful outcomes after non operative treatment were mostly related to early posttraumatic arthritis likely due to articular incongruity, hip joint instability, and muscle dysfunction. In our study, all the acetabular fractures are classified using standard investigations, operatively managed in indicated cases and followed up post-operatively with regards to improvement in clinical and radiological outcome. Out of 50 patients, 12 patients had excellent result, 24 patients had good result, 9 patients had fair result, and 5 patients had a poor result. Aims and Objectives 1. To study and analyze the outcomes of open reduction and internal fixation in patients with acetabular fractures in terms of radiology, clinical and functional outcomes. 2. To study the role of early range of motion exercises in the functional outcome.3. To study the complications associated with the surgical approaches. Materials and Methods 1. Type of study: Descriptive, case series, comparison study, partly retrospective and prospective. 2. The study was done to assess the clinical, radiological and functional outcome of patients with acetabular fractures treated with open reduction and internal fixation at Goa Medical College. 3. Study setting: Inpatient ward no 103,104,105, under Department of Orthopaedics, Goa Medical College. 4. Methods: All fractures have been classified using the Letournel and Judet classification. All the cases were followed up post operatively and were analyzed for radiological, functional and clinical outcome. The radiological outcome was evaluated with radiograph pelvis AP view, Obturator oblique view and Iliac oblique views. The functional outcome was evaluated with Merle d’Aubigne and Postel modified clinical grading system and Harris hip score.

Histological analysis of ACL reconstruction failures due to synthetic-ACL (LARS) ruptures.

Introduction:Anterior Cruciate Ligament (ACL) reconstruction is an established surgical procedure. Synthetic ligaments represent an option for ACL reconstruction. Their popularity declined for the raising concerns due to re-ruptures, knee synovitis and early arthritis related to I and II generation artificial ligaments. The introduction of a III generation synthetic ligament (Ligament Advanced Reinforcement System-LARS) permitted renewed interest in the adoption of this kind of graft. Main purpose of our study was to describe the histological findings on samples obtained from a consecutive series of ACL revision surgeries due to LARS ACL reconstruction failures. Secondary aim was to determine the reason for LARS rupture.Methods:In a period between 2016 and 2018 eleven patients underwent ACL revision surgery due to LARS ACL reconstruction failure. At the time of the arthroscopic procedure, samples of synovial membrane and remnants of the torn LARS were sent to the Pathological-Anatomy Institute of our Hospital for a histological analysis.Results:Histological analysis of the synovial tissues confirmed the arthroscopic evidence of synovitis mainly characterized by chronic inflammation with predominance of multinucleated giant cells. The adoption of polarized light microscopy revealed the presence of brightly bi-refractive material (LARS wear particles) in the synovial tissue; at higher magnification wear debris were detected inside the cytoplasma of multi nucleated cells. The histological analysis of the removed LARS revealed a surrounding typical foreign body reaction with poor signs of fibrovascular ingrowth of the synthetic ligament.Conclusions:Our findings could not clearly advocate a unique mechanism of LARS-ACL reconstruction failure: biologic issues (poor tissue ingrowth) and mechanical issues (fibers properties and tunnel position) probably concur in a multi factorial manner. ACL reconstruction using artificial ligaments can not be considered a simple surgery. Artificial augments require some expertise and could therefore achieve better results if used by skilled sport surgeons other than trainees or low volume surgeons. The Authors believe that ACL reconstruction with synthetic devices still have restricted indications for selected patients (e.g. elderly patients who require a fast recovery, professional athlete, autologous tendons not available and/or refusing donor tendons). Our study arises additional suspicion on the unresponsiveness of synthetic fibers and claim some concern in the implantation of synthetic devices. (www.actabiomedica.it)

Lack of association between clinical and ultrasound measures of disease activity in rheumatoid arthritis remission.

Objectives:The objective of this study was to assess the prevalence of ultrasound (US) abnormalities and association with clinical parameters in rheumatoid arthritis (RA) clinical remission.Methods:Patients with established RA in clinical remission (DAS28-CRP < 2.4) taking conventional synthetic disease-modifying anti-rheumatic drugs were recruited as part of the Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) Study. In addition, patients from the Newcastle Early Arthritis Clinic (NEAC) with early active RA (DAS28-CRP > 2.4) or seronegative non-inflammatory arthralgia (NIA) were studied as positive and negative controls, respectively. The association between individual dependent variables (synovial power Doppler and greyscale, tenosynovial greyscale, and erosions) and clinical parameters was assessed by multivariate ordinal logistic regression, with adjustment for multiple testing.Results:A total of 294 patients were included: 66 RA in remission, 146 active RA, and 82 NIA. Within the active RA group, significant associations were observed between swollen joint count and higher total synovial greyscale score (OR 1.17 95% CI 1.08–1.26, p < 0.001) and higher total synovial power Doppler score (OR 1.20, 95% CI 1.12–1.30, p < 0.001). No significant associations were observed for the NIA group. In the RA remission group, US abnormalities were frequently observed and comparable for both DAS28-CRP and 2011 ACR/EULAR Boolean remission, with no significant association with clinical parameters identified.Conclusion:We observed widespread subclinical US findings in RA patients in clinical remission, even when remission is defined using the stringent ACR/EULAR Boolean criteria. In contrast to active disease, synovial power Doppler failed to show significant association with any of the clinical parameters in RA remission. Our results suggest that clinical and US examinations are non-overlapping in evaluating RA remission, challenging the proposition of US-driven management strategies in this setting.

Comparative characteristics of early psoriatic arthritis with and without axial skeleton injury (a subanalysis of the all-Russian registry of patients with psoriatic arthritis)

Objective: to compare the clinical features of two groups of patients with early psoriatic arthritis (PsA): with the involvement of the axial skeleton and without axial lesion. Subjects and methods . Examinations were made in 95 patients (47 men and 48 women) with early PsA from the Russian registry, the diagnosis met the CASPAR criteria; their mean age was 36.5+10.7 years; the duration of arthritis was 12.1 + 10.3 months. In addition to the standard examination, all the patients underwent evaluation of inflammatory back pain (IBP) (ASAS criteria), pelvic radiography, and determination of HLA-B27; 79 patients had additionally magnetic resonance imaging (MRI) of the sacroiliac joints (SIJ). Active sacroiliitis (SI) detected on MRI (MRI-SI) was identified as bone marrow edema (osteitis) in the STIR mode. Radiographic SI on (rSI) was recorded if there were bilateral or unilateral changes (Kellgren grades >II or >III, respectively). The results of radiography and MRI were assessed by an independent radiologist. The disease activity in patients with IBP was evaluated by BASDAI. patients’ global assessment of disease activity (GADA) and assessment of pain intensity (PI) were made using a 100 mm visual analogue scale (VAS). The patients were divided into two groups: 1) those with axial lesion (axPsA), who had IBP, and/or rSI, and/or MRI-SI; 2) those without axial lesion, who had only peripheral PsA (pPsA). Results and discussion . IBP was found in 63 (66.3%) patients; it was transient, episodic in 35 (60.3%) from them. MRI-SI was detected in 28 (35.4%) from the 79 patients; rSI — in 29 (30.5%). The axPsA group included 65 (68.4%) patients and the pPsA group consisted of 30 (31.6%) patients. There was a preponderance of males in the axPsA group (60%) and that of females in the pPsA group (73.3%) ( р =0.003). The patients with axPsA were younger than those with pPsA (33.9+9.6 and 41.7+10.6 years, respectively; p=0.0007). They were more frequently HLA-B27 positive than pPSA patients: 47.6% (n=30) and 23.3% (n=7) (p=0.02); and had shorter duration of arthritis: 10.3+8.7 and 16.1 + 11.7 months, respectively (p = 0.008). In the axPsA group, of PI was worse than that in the pPsA group: GADA averaged 58.4+17.3 and 49.8+16.7 mm (p=0.02); PI >50 mm was observed in 44 (67.7%) and 13 (43.3%) patients, respectively [odds ratio (OR), 2.74; 95% confidence interval (CI), 1.13-6.67; p=0.026]. More severe skin lesions were seen in patients with axPsA than in those with pPsA: BSA >3% was detected in 24 (40.7%) and 4 (14.8%) patients (OR, 3.94; 95% CI, 1.21-12.86; p=0.023); the median PASI was 9.7 [6.6; 21.5] and 5.0 [0.0; 6.4] respectively (p=0.005). The patients with axPsA showed higher C-reactive protein (CRP) values than those with pPsA: CRP >5 mg/L was found in 58 (89.3%) and 19 (63.3%) patients, respectively (OR, 4.80; 95% CI, 1.63-14.13; p=0.004). Conclusion. The targeted examination of PsA patients revealed axial lesion in 68% from them; delayed diagnosis was generally associated with the inconsistent character of IBP. Among the patients with axPsA, there are significantly more males, younger adults, and HLA-B27 carriers. With the involvement of the axial skeleton, there was a more severe course of the disease: worse PI, a greater severity of skin lesions, and higher CRP levels. Considering the need for early diagnosis of axPsA for the timely use of biological agents, studies of this problem should be continued using large patient cohorts.

Is Referring Early Arthritis Patients within 6 Weeks Associated with Better Long-Term Outcomes than Referring within 12 Weeks after Symptom Onset? – Investigating the Evidence for the First EULAR Recommendation for Early Arthritis

Background: EULAR-recommendations for management of early arthritis formulated that patients should be referred to, and seen by a rheumatologist, within 6-weeks after symptom onset. Because implementation provides challenges, and evidence supporting that referral ≤6 weeks is better than e.g. <12-weeks is missing, we investigated if ≤6-weeks relates to improved long-term outcomes, measured with sustained DMARD-free remission (SDFR) and radiographic progression. Methods: Consecutive 1987-RA patients of the Leiden EAC (n=1025) and ESPOIR (n=514) were studied during median 7 and 10 years follow-up. Patients were categorized on duration between symptom onset and first encounter with a rheumatologist; ≤6, 7-12, and >12-weeks. Multivariable Cox regression (SDFR), linear mixed models (radiographic progression), and meta-analyses were used. Findings: Leiden RA-patients encountered the rheumatologist within 6-weeks obtained SDFR more often than patients seen within 7-12-weeks (HR 1·59, 95%CI:1·02-2·49), and >12-weeks (HR 1·54, 95%CI:1·04-2·29). In ESPOIR, similar but non-significant effects were observed; meta-analysis showed that within 6-weeks was better than 7-12-weeks (HR 1·69, 95%CI:1·10-2·57) and >12-weeks (HR 1·67, 95%CI:1·08-2·58). Patients encountered the rheumatologist within 6-weeks had similar radiographic progression than those seen 7-12-weeks, in any cohort, or meta-analysis. Interpretation: Scientific evidence underlying the first EULAR recommendation depends on the outcome of interest; visiting a rheumatologist within 6-weeks of symptom-onset had clear benefits for achieving SDFR, but not for radiographic progression. Funding Statement: EAC was supported by the European Research Council (ERC-Starting grant, No714312) and the Dutch Arthritis Society. ESPOIR was funded by an unrestricted grant from Merck Sharp and Dohme (MSD) for the first 5 years. Additionally, two INSERM grants, The French Society of Rheumatology, Pfizer, Abbvie, Lilly, and Sanofi supported ESPOIR. Declaration of Interests: The authors stated: None. Ethics Approval Statement: Written informed consent was obtained by all participants and both cohorts received approval by their ethical committees.

Association Between Vitamin D Deficiency and Disease Activity, Disability, and Radiographic Progression in Early Rheumatoid Arthritis: The ESPOIR Cohort.

To evaluate the association of baseline serum level of vitamin D with disease activity, disability, and radiographic damage over the first year in early rheumatoid arthritis (RA). Among early arthritis patients included in the ESPOIR cohort, patients with early RA were evaluated. Levels of 25-hydroxy vitamin D2 and D3 were measured at baseline. Baseline associations between vitamin D level and 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR), Health Assessment Questionnaire-Disability Index (HAQ-DI), and van der Heijde modified total Sharp score (mTSS) were assessed. Bivariate analysis was used to assess the association between vitamin D level and radiographic progression (mTSS increased by ≥ 1 point) or disability (HAQ-DI ≥ 0.5) over 12 months. Forward stepwise multiple logistic regression was used to evaluate the independent association of baseline variables and outcomes. Among 813 patients with early arthritis, data for 645 patients with RA were analyzed. Vitamin D level was < 10 ng/mL (deficiency, group 1), 10-29.9 ng/mL (low level, group 2), and ≥ 30 ng/mL (normal, group 3) for 114 (17.7%), 415 (64.54%), and 114 (17.7%) patients, respectively. At baseline, DAS28-ESR and HAQ-DI were higher with vitamin D deficiency compared with groups 2 and 3 combined (P = 0.007 and P = 0.001, respectively), as was mean mTSS, but not significantly (p = 0.076). On multivariate analysis, baseline vitamin D deficiency was associated with HAQ-DI at 6 months (OR 1.70) and mTSS at 12 months (OR 1.76). Vitamin D deficiency was associated with more active and severe disease at baseline and may predict disability and radiographic progression over 1 year in early RA patients. [ClinicalTrials.gov: NCT03666091].

GOTHA - The Early Arthritis and Psoriasis Study of Region Västra Götaland, Sweden

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Increased monohexosylceramide levels in the serum of established rheumatoid arthritis patients.

To identify serum sphingolipids that could act as candidate biomarkers in RA. We performed lipidomic analyses in the serum of 82 participants: 19 established RA patients, 18 untreated early RA patients, 13 untreated early arthritis patients not fulfilling the classification criteria for RA, 12 established SpA patients and 20 controls. We compared the lipid levels from the different patient groups with the control group through multiple-regression analyses controlling for age at diagnosis, gender and medication (cDMARDs and corticoids). Established RA patients had significantly increased levels of sphingosine, monohexosylceramide and ceramide compared with controls, when controlling for age and gender. Monohexosylceramide levels remained significantly increased when additionally controlling for medication. On the contrary, SpA patients had significantly decreased levels of ceramide, in both analyses. We observed a detectable increase in the levels of certain sphingolipids in the serum of established RA patients when compared with controls, in line with previous observations in the synovial fluid. Such findings provide further evidence that sphingolipids may play a key role in the pathophysiology of RA.

Variation and implications of treatment decisions in early rheumatoid arthritis: results from a nationwide cohort study.

Trial data have provided an evidence base to guide early treatment in RA. Few studies have investigated rheumatologists' adherence to guidelines, and subsequent impact on outcomes. The objectives of this study are to characterize baseline prescribing for patients with RA across the National Health Service, identifying treatment decisions that associate with patient outcomes. A nationwide audit of RA collected information on treatment choices, DAS and sociodemographic factors at baseline. Treatment response was assessed at 3 months. Multilevel regression models were used to characterize departmental variations in prescribing. Heat maps were used to visualize geographical variation. Mixed effects regression models were constructed to assess the relationship between treatment decisions and disease outcomes, adjusting for patient and department level covariates. A total of 7154 patients with a diagnosis of RA were recruited from 136 departments. There was broad variation in prescribing choices, even between departments close to one another, with evidence of substantial deviation from guidelines. Over 75% of patients received glucocorticoids, fewer than half received combination conventional DMARDs. Early glucocorticoid therapy associated with achieving a good treatment response [odds ratio 1.93 (95% CI 1.31, 2.84), P-value = 0.001]. The association was maintained following propensity modelling and imputation. Guideline adherence varies between departments and cannot be explained by case-mix alone. Departments that prescribe early adjunctive steroid achieve better short-term outcomes. Further research should work to ensure that the early arthritis evidence base translates into better outcomes for patients.

Improved RA classification among early arthritis patients with the concordant presence of three RA autoantibodies: analysis in two early arthritis clinics

BackgroundThe patients with RA benefit from early identification soon after the first clinical symptoms appear. The 2010 ACR/EULAR classification criteria were developed to fulfill this need and their application has been demonstrated to be effective. However, there is still room for improvement. Therefore, we aimed to evaluate the potential of the concordant presence of RF, anti-CCP and anti-carbamylated protein antibodies to improve current RA classification among early arthritis (EA) patients.MethodsData from the first visit of 1057 patients in two EA prospective cohorts were used. The serological scores from the 2010 ACR/EULAR criteria and the concordant presence of the three RA autoantibodies were assessed relative to a gold standard consisting of the RA classification with the 1987 ACR criteria at the 2 years of follow-up.ResultsThe concordant presence of three antibodies showed predictive characteristics allowing for direct classification as RA (positive predictive value = 96.1% and OR = 80.9). They were significantly better than the corresponding to the high antibody titers defined as in the 2010 classification criteria (PPV = 88.8%, OR = 26.1). In addition, the concordant presence of two antibodies was also very informative (PPV = 82.3%, OR = 15.1). These results allowed devising a scoring system based only on antibody concordance that displayed similar overall performance as the serological scoring system of the 2010 criteria. However, the best classification was obtained combining the concordance and 2010 serological systems, a combination with a significant contribution from each of the two systems.DiscussionThe concordant presence of RA autoantibodies showed an independent contribution to the classification of EA patients that permitted increased discrimination and precision.

Early Diagnosis Of Inflammatory Arthritis By Primary Care Physicians Following Training By A Rheumatologist.

BackgroundEarly diagnosis and therapeutic management of inflammatory arthritis (IA) is crucial for minimizing disease progression and improving outcomes. We recently developed the New Early Arthritis Referral Criteria to help improve the detection of suspected early IA via musculoskeletal (MSK) examination. The present study aimed to evaluate the agreement between rheumatologists and primary care physicians (PCPs) trained by rheumatologists in detecting IA when applying the standardized MSK examination techniques used to develop this criteria in a real-world setting in Jeddah, Saudi Arabia.MethodsThis quasi-experimental study was conducted in 4 primary health centers and involved 30 PCPs and 3 rheumatologists. All PCPs were trained by rheumatologists to apply the standardized MSK examination techniques used to develop the New Early Arthritis Referral Criteria. Patients were eligible if they were >18 years of age and presented with small-joint pain that persisted for >6 weeks. Patients were excluded if they had prior diagnosis of osteoarthritis, hand fractures, or rheumatic disease associated with IA. All patients were examined separately by a PCP and a rheumatologist, with the findings compared via kappa statistics and the rheumatologist’s findings considered the “gold standard”.ResultsData from 202 of the 203 enrolled patients were analyzed. There was fair-to-moderate agreement between PCPs and rheumatologists when assessing swelling of the small joints and wrist of the right side (range of kappa: 0.14–0.41) and low-to-moderate agreement in similar examinations of the left side (range of kappa: 0.04–0.42). Assessments of joint tenderness showed fair-to-moderate agreement for both the right side (range of kappa: 0.22–0.47) and left side (range of kappa: 0.24–0.45). P-values were significant for virtually all comparisons.ConclusionMSK examinations by PCPs showed a promising extent of agreement in detecting IA with those by rheumatologists following training. Refinement of the standardized training process could further improve accuracy and help PCPs to confidently identify cases of early IA, thus allowing earlier intervention than is typical in this setting.

CD4+ CCR6+ Tcells, but not γδ Tcells, are important for the IL-23R-dependent progression of antigen-induced inflammatory arthritis in mice.

IL‐23 plays an important role in the development of arthritis and the IL‐23 receptor (IL‐23R) is expressed on different types of T cells. However, it is not fully clear which IL‐23R+ T cells are critical in driving T cell‐mediated synovitis. We demonstrate, using knock‐in IL‐23R‐GFP reporter (IL‐23RGFP/+) mice, that CD4+CCR6+ T cells and γδ T cells, but not CD8+ T cells, express the IL‐23R(GFP). During early arthritis, IL‐23R(GFP)+CD4+CCR6+ T cells, but not IL‐23R(GFP)+ γδ T cells, were present in the inflamed joints. IL‐23RGFP/+ mice were bred as homozygotes to obtain IL‐23RGFP/GFP (IL‐23R deficient/IL‐23R−/−) mice, which express GFP under the IL‐23R promotor. Arthritis progression and joint damage were significantly milder in IL‐23R−/− mice, which revealed less IL‐17A+ cells in their lymphoid tissues. Surprisingly, IL‐23R−/− mice had increased numbers of IL‐23R(GFP)+CD4+CCR6+ and CCR7+CD4+CCR6+ T cells in their spleen compared to WT, and IL‐23 suppressed CCR7 expression in vitro. However, IL‐23R(GFP)+CD4+CCR6+ T cells were present in the synovium of IL‐23R−/− mice at day 4. Finally, adoptive transfer experiments revealed that CD4+CCR6+ T cells and not γδ T cells drive arthritis progression. These data suggest that IL‐23R‐dependent T cell‐mediated synovitis is dependent on CD4+CCR6+ T cells and not on γδ T cells.