Progression Of Joint Damage Research Articles

Soluble vascular cell adhesion molecular-1 is a potential biological indicator of hemophilic arthropathy.

Hemophilic arthropathy is the most common chronic complication in patients with hemophilia. The pathogenesis of hemophilic arthropathy involves the inflammatory processes associated with rheumatoid arthritis (RA). Determining the severity and/or progression of joint damage is crucial when evaluating the effect of treatment modalities. Identifying reliable biomarkers in the peripheral blood of patients with hemophilic arthropathy may be beneficial in clinical practice. Circulating soluble vascular cell adhesion molecule-1 (sVCAM-1), E-selectin, and P-selectin levels are elevated in patients with RA. Our study investigated whether these soluble adhesion molecules can be used as biological indicators in the course of joint damage in patients with hemophilia A.Patients with hemophilia A (mild, moderate, and severe) were enrolled. The plasma levels of sVCAM-1, E-selectin, and P-selectin in patients with hemophilia A and control were measured using specific enzyme-linked immunosorbent assay kits. Joint damages were evaluated using Pettersson scores.No statistically significant differences were observed in E-selectin and P-selectin levels between patients and controls. The sVCAM-1 level was significantly higher in patients with hemophilia A than in controls. The differences remained significant in patients with severe hemophilia A but not in patients with mild or moderate hemophilia A. The degree of hemophilic arthropathy was evaluated using Pettersson scores, and a score higher than 5 indicated marked arthropathy. Patients with more than 1 joint with marked arthropathy showed significantly higher sVCAM-1 levels.sVCAM-1 levels in patients with hemophilia A are associated with the severity of hemophilic arthropathy.

A study of acute and chronic tissue changes in surgical and traumatically-induced experimental models of knee joint injury using magnetic resonance imaging and micro-computed tomography.

The objective of this study was to monitor the progression of joint damage in two animal models of knee joint trauma using two non-invasive, clinically available imaging modalities. A 3-T clinical magnet and micro-computed tomography (μCT) was used to document changes immediately following injury (acute) and post-injury (chronic) at time points of 4, 8, or 12 weeks. Joint damage was recorded at dissection and compared to the chronic magnetic resonance imaging (MRI) record. Fifteen Flemish Giant rabbits were subjected to a single tibiofemoral compressive impact (ACLF), and 18 underwent a combination of anterior cruciate ligament (ACL) and meniscal transection (mACLT). All ACLF animals experienced ACL rupture, and 13 also experienced acute meniscal damage. All ACLF and mACLT animals showed meniscal and articular cartilage damages at dissection. Meniscal damage was documented as early as 4 weeks and worsened in 87% of the ACLF animals and 71% of the mACLT animals. Acute cartilage damage also developed further and increased in occurrence with time in both models. A progressive decrease in bone quantity and quality was documented in both models. The MRI data closely aligned with dissection notes suggesting this clinical tool may be a non-invasive method for documenting joint damage in lapine models of knee joint trauma. The study investigates the acute to chronic progression of meniscal and cartilage damage at various time points, and chronic changes to the underlying bone in two models of posttraumatic osteoarthritis (PTOA), and highlights the dependency of the model on the location, type, and progression of damage over time.

Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial

Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm2) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of defect filling and development of repair tissue approaching the composition of native cartilage. Hyaline-like cartilage tissues, engineered from autologous nasal chondrocytes, can be used clinically for repair of articular cartilage defects in the knee. Future studies are warranted to assess efficacy in large controlled trials and to investigate an extension of indications to early degenerative states or to other joints. Deutsche Arthrose-Hilfe.

Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study

BackgroundBaricitinib is an oral, reversible, selective Janus kinase 1 and 2 inhibitor.MethodsIn this phase III, double-blind 24-week study, 684 biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with rheumatoid arthritis and inadequate...

Radiographic changes and factors associated with subsequent progression of damage in weight-bearing joints of patients with rheumatoid arthritis under TNF-blocking therapies—three-year observational study

Objectives: The long-term effects of tumor necrosis factor (TNF)-blocking therapies on weight-bearing joints in patients with rheumatoid arthritis (RA) have not been fully characterized. The purpose of this study was to assess the radiographic changes of weight-bearing joints in patients with RA during 3-year of TNF-blocking therapies and to identify factors related to the progression of joint damage.Methods: Changes in clinical variables and radiological findings in 243 weight-bearing joints (63 hips, 54 knees, 71 ankles, and 55 subtalar joints) in 38 consecutive patients were investigated during three years of treatment with TNF-blocking agents. Multivariate logistic regression analysis was used to identify risk factors for the progression of weight-bearing joint damage.Results: Seventeen (14.5%) of proximal weight-bearing joints (hips and knees) showed apparent radiographic progression during three years of treatment, whereas none of the proximal weight-bearing joints showed radiographic evidence of improvement or repair. In contrast, distal weight-bearing joints (ankle and subtalar joints) displayed radiographic progression and improvement in 20 (15.9%) and 8 (6.3%) joints, respectively. Multivariate logistic analysis for proximal weight-bearing joints identified the baseline Larsen grade (p < 0.001, OR:24.85, 95%CI: 5.07–121.79) and disease activity at one year after treatment (p = 0.003, OR:3.34, 95%CI:1.50–7.46) as independent factors associated with the progression of joint damage. On the other hand, multivariate analysis for distal weight-bearing joints identified disease activity at one year after treatment (p < 0.001, OR:2.13, 95%CI:1.43–3.18) as an independent factor related to the progression of damage.Conclusions: Baseline Larsen grade was strongly associated with the progression of damage in the proximal weight-bearing joints. Disease activity after treatment was an independent factor for progression of damage in proximal and distal weight-bearing joints. Early treatment with TNF-blocking agents and tight control of disease activity are necessary to prevent the progression of damage of the weight-bearing joints.

Disease activity states of the DAPSA, a psoriatic arthritis specific instrument, are valid against functional status and structural progression

BackgroundRecently, disease activity states were developed for the Disease Activity index for PSoriatic Arthritis (DAPSA). Here, we assess if different DAPSA disease activity states are associated with different degrees of...

GRAPPA 2015 Research and Education Project Reports.

At the 2015 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), attendees were presented with brief updates on several ongoing initiatives, including educational projects. Updates were presented on the treatment recommendations project, the development of simple criteria to identify inflammatory musculoskeletal disease, new patient/physician Delphi exercises, and BIODAM (identifying biomarkers that predict progressive structural joint damage). The publication committee also gave a report. Herein we summarize those project updates.

Differential synovial expression patterns in early osteoarthritis patients are associated with pain and with progression of joint damage

Differential synovial expression patterns in early osteoarthritis patients are associated with pain and with progression of joint damage

Have radiographic progression rates in early rheumatoid arthritis changed? A systematic review and meta-analysis of long-term cohorts.

To evaluate, firstly, all published data on baseline and annual progression rates of radiographic damage from all longitudinal observational cohorts, and secondly, the association of standard clinical and laboratory parameters with long-term radiographic joint damage. A comprehensive search of the literature from 1975 to 2014, using PubMed, SCOPUS and Cochrane databases, identified a total of 28 studies that investigated long-term radiographic progression, and 41 studies investigating predictors of long-term radiographic progression. This was submitted and approved by PROSPERO in February 2014 (Registration Number: CRD42014007589). Meta-analysis indicated an overall baseline rate of 2.02%, and a yearly increase of 1.08% of maximum damage. Stratified analysis found that baseline radiographic scores did not differ significantly between cohorts recruiting patients pre- and post-1990 (2.01% vs 2.03%; P > 0.01); however, the annual rate of progression was significantly reduced in the post-1990 cohorts (0.68% vs 1.50%; P < 0.05). High levels of acute phase markers, baseline radiographic damage, anti-CCP and RF positivity remain consistently predictive of long-term radiographic joint damage. Critical changes in treatment practices over the last three decades are likely to explain the reduction in the long-term progression of structural joint damage. Acute phase markers and presence of RF/anti-CCP are strongly associated with increased radiographic progression.

Factors associated with change in radiographic damage scores in gout: a prospective observational study

Background/aimsRadiographic damage is frequently observed in patients with longstanding gout. The aim of this prospective observational study was to determine factors associated with change in radiographic damage scores in gout.MethodsPeople...

Association between Wnt inhibitory factor-1 expression levels in articular cartilage and the disease severity of patients with osteoarthritis of the knee.

Wnt inhibitory factor (WIF)-1 is a potent extracellular Wnt antagonist which may be used as a potential molecular therapy for the treatment of inflammatory and autoimmune diseases. Although previous studies have demonstrated that WIF-1 has a protective role in experimental studies of arthritis, its role in the various disease grades of osteoarthritis (OA) remains unclear. A total of 40 patients with various stages of primary OA of the knee and 10 control subjects were enrolled in the present study. Articular cartilage specimens were harvested from subjects following total knee arthroplasty or knee above amputation. Disease severity was determined according to Modified Mankin score and cartilage tissues were ascribed to four groups: Normal, mild, moderate and severe lesions. WIF-1 expression levels in articular cartilage were measured using immunohistochemical techniques. WIF-1 expression levels were detected in all cartilage tissues. As compared with the controls, patients with OA exhibited significantly decreased WIF-1 expression levels in the articular cartilage (0.19±0.05 vs. 0.26±0.04; P<0.01). Furthermore, articular cartilage WIF-1 expression levels in the moderate and severe lesion groups were significantly reduced, as compared with the controls (P<0.01) and mild lesion group (P<0.05). Subsequent analysis demonstrated that articular cartilage WIF-1 expression levels were negatively correlated with the severity of disease (r=-0.896, P<0.001). In conclusion, the results of the present study suggested that WIF-1 expression levels in articular cartilage may be negatively associated with progressive joint damage in patients with OA of the knee; therefore, WIF-1 expression may be a potential indictor for monitoring OA disease severity.

A study on efficacy and safety of etanercept in patients with rheumatoid arthritis

Aim and objective: To assess the efficacy of Etanercept and also to evaluate the safety profile of Etanercept in patients with Rheumatoid arthritis. The main objectives of the study are to evaluate the drug safety and efficacy among the Rheumatoid arthritis patients. And to monitor the ADRs observed in Rheumatoid arthritis patients with Etanercept. Materials and Methods: Study was carried out in a 300 bedded tertiary care hospital. The department selected for the study was orthopaedics. This method involves prospective observational analysis of Efficacy and safety of Etanercept in patients with Rheumatoid arthritis. The study was carried out by the collection and documentation of general information of the patient including personal history, past medical history, past medication history, lab investigations and treatment pain will be analysed by using visual analog scale(vas). ADR’s were assessed by using Naranjo adverse drug reaction probability scale. The whole procedure was carried out in Rheumatoid arthritis patients who received Etanercept without any alteration in therapy. Result and Discussion: This study on sample size of 35 was carried out to assess the short term safety and efficacy of Etanercept. Moreland et al compared placebo, ETN 10 mg twice weekly (ETN20), and ETN 25 mg twice weekly (ETN50) in patients with long-standing RA and an inadequate response to DMARDs. Although both treatment arms were significantly better than placebo, as measured by American College of Rheumatology. The study conducted by Elizabeth Mary Curtis et al., shows that Etanercept is a safe and well-tolerated treatment for RA, And another study conducted by Boulos Haraoui et al, study shows that Etanercept is both safe and effective to use in RA. Etanercept has been shown not only to reduce disease activity but also to limit progression of joint damage in early and late disease which are similar to our study. Conclusion: This study concludes incidence of rate of patients in the age group of 50 – 59 years were mostly affected by Rheumatiod arthritis compared to other age groups. The male patients were found to be affected more with rheumatoid arthritis than female patients. The study made use of 25mg Eternacept for the above obtained results. This could also be carried out using 50mg Eternacept and evaluated on the same. There was a decrease in pain VAS scale confirming the efficacy and safety of Etanercept. In the future, this study could be further extended to a combination therapy over longer duration of time for better results.

The efficacy of abatacept in Japanese patients with rheumatoid arthritis: 104 weeks radiographic and clinical results in clinical practice

Objective: We aimed to assess the efficacy of abatacept in Japanese patients with rheumatoid arthritis (RA) in clinical practice.Methods: We examined 92 patients who received abatacept for 104 weeks. Analysis of radiographic efficacy was conducted using van der Heijde-modified total Sharp score (mTSS). Disease activity score was assessed using disease activity score in 28 joints (DAS28) and simplified disease activity index (SDAI) by last observation carried forward.Results: The change in mTSS was 0.61 at 52 weeks and 0.27 at 52–104 weeks. Structural remission occurred in 64.9% at 52 weeks and 76.6% at 104 weeks. The significant risk factors for joint damage progression at 52 weeks were prednisolone use, baseline C-reactive protein level (CRP), and erythrocyte sedimentation rate (ESR), as well as average DAS28-CRP and DAS28-ESR scores, SDAI, CRP, ESR, and matrix metalloproteinase-3 (MMP-3) levels. The clinical remission rates were 47.8% by DAS28-CRP, 39.1% by DAS28-ESR, and 30.4% by SDAI at 52 weeks, were 59.8% by DAS28-CRP, 48.9% by DAS28-ESR, and 43.5% by SDAI at 104 weeks.Conclusion: This study suggested efficacy of abatacept treatment in Japanese patient with RA for 104 weeks in daily clinical practice. Abatacept lead to suppress joint destruction for 104 weeks.

Radiographic progression of large joint damage in patients with rheumatoid arthritis treated with biological disease-modifying anti-rheumatic drugs

Objectives: Radiographic progression of damage to the small joints in patients with rheumatoid arthritis (RA) is well known; however, it has not been studied fully in the large joints. In this study, we looked at the prevalence of radiographic progression of large joint damage in patients with RA treated with biological disease-modifying anti-rheumatic drugs (bDMARDs).Methods: A total of 273 large joints in the upper and lower extremities of 67 patients with RA treated with bDMARDs were investigated. Radiographs for tender and/or swollen large joints were taken at least twice during the study period (mean 18.6 months), and the progression of damage was evaluated.Results: Progressive damage was found in 20.9% of patients and 6.2% of joints. A multivariate analysis revealed that the Larsen grade (LG) alone was a risk factor for progressive damage. The LG cutoff value was determined to be 2.5 (sensitivity: 0.529, specificity: 0.805).Conclusions: The only factor to predict progressive damage was the LG of the joints with symptoms, and the damage must be stopped within LG II. Regular radiographic examinations for large joints should be performed in addition to routine examinations for small joints, such as the hand and foot.

Comparison of Short-Term Tertiary Prophylaxis at Low-Dose and Intermediate-Dose for Adults with Severe Hemophilia a in China

▪Background: Some studies had indicated that the joint damage progression could not be prevented by low-dose prophylaxis regimen though it had been practiced and achieved good outcomes as well as largely reduced bleedings. we initiated a retrospective study to compare the different outcomes between low-dose and intermediate-dose regimen of tertiary prophylaxis for adults with severe hemophilia A.Methods: Data collected from the hemophilia treatment centre at Nanfang hospital from July 2010 to February 2015 ( median 2 years of follow-up), a total of 40 adult patients with severe hemophilia A (FVIII < 1%) who are receiving prophylaxis treatment≥1 year and treatment data available were eligible for enrollment in the study, including 25 patients in low-dose regimen(F‡[8-15 IU/kg 1-2times weekly or weekly<30 IU/kg), and 15 patients in intermediate-dose regimen( F‡[ 15-20 IU/kg 2-3 times weekly or weekly≥40IU/kg and <75 IU/kg). Collect the data with patients' characteristics, previous condition and treatment, treatment efficacy indexFannual bleeding rate(ABR), annual joint bleeding rate(AJBR), number of target joint, annual target joint bleeding rate, annual severe bleeding event, etc.), FVIII consumption. Use FISH scoring system to evaluate patients' joint status, use the difference between the beginning of this study and one year ago of FISH score to represent the improvement of joint function. To analyze the joint function in various subgroups(joint bleeding rate ≤5 times or >5 times) under prophylaxis treatment. Screening out patients whose dosage and frequency adherence both >75% in two groups, including 15 patients in low-dose regimen and 14 patients in intermediate-dose regimen, observed the situation that breakthrough bleeding events occurred in different time period after clotting factors' injection and calculate the proportion.Results: 1. There were no statistical differences between two groups in age, weight, age at first bleeding, age at first treatment, family history of hemophilia and history of hepatitis. (the range of p-value was 0.221-1.000). 2. Intermediate-dose prophylaxis regimen reduced ABR than the low-dose regimen (median 13 vs. 5.5, P=0.000), as well as AJBR (median 10 vs. 4, p=0.001) and the annual target joint bleeding rate (median 8 vs. 3.5, p=0.002) .Reduced median annual absent days was found in intermediate-dose regimen group (median 7.5 vs. 0, p=0.005). In terms of total annual usages of FVIII, the intermediate-dose regimen group increased 35% than low-dose regimen group(2630 IU/kg/year vs.1950 IU/kg/year,P=0.000), but decreased 63% ABR, 60% AJBR and 56% annual target joint bleeding than low-dose regimen group. There was no statistical differences between low-dose and intermediate-dose groups in terms of target joint numbers (median 1 vs.1,P=0.579) and annual severe bleeding events(median 0 vs.0, P=0.911). 3. There was statistical differences between two groups on the improvement of FISH(P=0.008). The proportion that patients' annual joint bleeding rate ≤5 in low dose and intermediate-dose group were 12% and 73.3%. When AJBR ≤5, the mean improvement of Fish score of low-dose and intermediate-dose group was 0.33 and 1.18, When AJBR>5, the mean score was -0.09 and 1.00 respectively, while the joint function still improved in intermediate-dose group.3. The low-dose group had higher proportion of breakthrough bleeding in 24-48h after FVIII injection (median 45.5% vs.27.95%, P=0.000), while intermediate-dose group got higher proportion in more than 48h after FVIII injection (median 60% vs.43.75%,P=0.001).Conclusion: 1. Compared to low-dose prophylaxis regimen, the ABR, AJBR, annual target joint bleeding rate, annual absent days and joint functionwere significantly decreased in patients treated with intermediate-dose regimen.2. It is indicated the intermediate-dose prophylaxis treatment would be better in long-term effect than low-dose regimenin improving joint function. 3. The low-dose group had higher proportion of breakthrough bleeding in 24-48h after FVIII injection, while intermediate-dose group got higher proportion in more than 48h after FVIII injection. Once every other day regimen is beneficial to further reduce bleedings in intermediate-dose prophylaxis treatment. DisclosuresNo relevant conflicts of interest to declare.

Annual Evaluations of MRI Findings of Hemophilia Arthropathy in 7 Years

ObjectiveRecently, hemophilia care has been advanced with regular factor VIII replacement (prophylaxis) to prevent or postpone joint damage. It have been needed an accurate monitoring system for the evaluation of hemophilic arthropathy. Conventional radiography has been used to objectively evaluate hemophilic arthropathy. However, it visualizes primarily bone lesions that appear late in the process of hemophilic arthropathy. Magnetic resonance imaging (MRI) had been considered to accurately evaluate the early changes of these joint damages in hemophilic arthropathy.We present our experiences of 7 years annual MRI assessment of arthropathy of the Japanese children with hemophilia, who were treated with sencondary prophylaxis or on demand therapy in comparison with conventional radiographic assessment.MethodsFrom 2007 to 2013, 10 children , 7 hemophilia A and 3 hemophilia B ,were enrolled in this study. One patient was treated with primary prophylaxis , 6 pts with secondary prophylaxis, 4 pts with on demand therapy. We made annual MRI and X ray examinations to of hemophilic arthropathy assessments of 37 joints (bilateral knees and ankles of every patient). We used a complete MRI protocol, including T1-weighted, T2*-weighted and short tau inversion recovery (STIR), GRE (gradient echo) T2*) sequences in all the joints. Assessmen of MRI was done with according to the compatible MRI scoring system (Haemophilia 2005, 11, 116 - 122), and X-ray radiographic assesment was according to the Pettersson system.ResultsThe damage grade of MRI findings were severe damage grade ; 5 joints, moderate grade ; 4 joints, mild grade ; 21 joints, no damage ; 7 joints. The damage grade of two joint were reduced and that of one joint was increased in 7 years. The progressive joint damage was found in 11 years boy with severe hemophilia A and he had been treated with on demand therapy .Of the 173 studied joints, 49 (29.5%) had normal MRI findings, and 124 (70.5%) showed a various ranges of abnormalities. 58 joints (35.3%) had progressive damages in 7 years. Synovial hyperplasia and/or hemosiderin deposition was the main MRI findings in the affected joints (105/116, 90.5%). Cysts and/or erosions were the second in order finding (66/116, 56.9%). Although synovial hyperplasia was present, hemosiderin was not observed in 17 of 105 (16.2 %) joints, which suffered a few hemarthroses within the last 2 years. On X-ray radiographic evaluations, 57 of the 173 studied joints (34.3%) had a zero Pettersson score (0); however, 50% of them (29/57) presented with MRI alterations. The remaining 108 joints had radiological scores ranging between 2 and 13 points, nonetheless, in 70% (72/108) of cases MRI revealed more profound alterations than those observed by X-ray findings.ConclusionWe considered that MRI assessment of patients' joints could identify the early changes of hemophilic arthropathy. But, this study is consisting of small numbers of joints observation, further studies are needed to confirm these findings. DisclosuresNo relevant conflicts of interest to declare.

Disease flares in rheumatoid arthritis are associated with joint damage progression and disability: 10-year results from the BeSt study.

IntroductionFlares in patients with rheumatoid arthritis are suggested to sometimes spontaneously resolve. Targeted therapy could then entail possible overtreatment. We aimed to determine the flare prevalence in patients who are treated-to-target and to evaluate associations between flares and patient-reported outcomes and radiographic progression.MethodsIn the BeSt study, 508 patients were treated-to-target for 10 years. After initial treatment adjustments to achieve disease activity score ≤2.4, a flare was defined from the second year of follow-up onwards, according to three definitions. The first definition is a disease activity score >2.4 with an increase of ≥0.6 regardless of the previous disease activity score. The other definitions will be described in the manuscript.ResultsThe flare prevalence was 4–11 % per visit; 67 % of the patients experienced ≥1 flare during 9 years of treatment (median 0 per patient per year). During a flare, functional ability decreased with a mean difference of 0.25 in health assessment questionnaire (p < 0.001), and the odds ratios (95 % confidence intervals) for an increase in patients’ assessment of disease activity, pain and morning stiffness of ≥20 mm on a visual analogue scale were 8.5 (7.3–9.8), 8.4 (7.2–9.7) and 5.6 (4.8–6.6), respectively, compared to the absence of a flare. The odds ratio for radiographic progression was 1.7 (1.1–2.8) in a year with a flare compared to a year without a flare. The more flares a patient experienced, the higher the health assessment questionnaire at year 10 (p < 0.001) and the more radiographic progression from baseline to year 10 (p = 0.005).ConclusionFlares were associated with concurrent increase in patient’s assessment of disease activity, pain and morning stiffness, functional deterioration and development of radiographic progression with a dose–response-effect, both during the flare and long term. This suggests that intensifying treatment during a flare outweighs the risk of possible overtreatment.Trial registrationDutch trial registry NTR262 (7 September 2005) and NTR265 (8 September 2005).

MRI evidence of persistent joint inflammation and progressive joint damage despite clinical remission during treatment of early rheumatoid arthritis

Objectives: To determine the value of magnetic resonance imaging (MRI) of bones and joints in patients with recent-onset rheumatoid arthritis (RA) treated for 2 years from diagnosis with disease-modifying anti-rheumatic drugs (DMARDs) and glucocorticoids.Method: Thirteen patients with early RA were treated according to clinical practice and followed with MRI, radiographs, and Disease Activity Score calculated on 28 joints (DAS28) at inclusion (baseline) and after 1, 4, 7, 13, and 25 months. MRI of the dominant wrist and metacarpophalangeal (MCP) joints were assessed for synovitis, bone oedema, and erosions using the RA MRI Score (RAMRIS) and for tenosynovitis by an MRI tenosynovitis scoring method. Radiographs were assessed by the van der Heijde modified Sharp score (SHS). Clinical remission was defined by a DAS28 < 2.6.Results: MRI at baseline detected inflammation in joints and tendons in all patients as well as erosions in 10 out of 13 patients. Over time, the erosion score increased while the synovitis and tenosynovitis scores remained almost unchanged. Bone oedema strongly correlated with synovitis. Synovitis and tenosynovitis correlated well with the erosion score at baseline but not thereafter. The MRI changes showed that joint damage started early and continued in the presence of persistent synovial and tenosynovial inflammation.Conclusions: The observations made in this small study suggest that the treatment goal of ‘clinical remission’ should be supplemented by a ‘joint remission’ goal. To this end, MRI is an appropriate tool. Further studies are needed to evaluate the optimal use of MRI in early RA.

Anti- Cyclic Citrullinated Peptide Antibodies: Clinical utility and their role as early prognostic markers in Erosive Rheumatoid Arthritis.

Objectives: To assess the diagnosticutilityofanti- cyclic citrullinated protein antibody (anti-CCP) in comparison to rheumatoid factor (RF) in diagnosis of rheumatoid arthritis (RA) and to determine its prognostic value in erosive rheumatoid arthritis.Materials and Methods: The study included 60 patients with clinically suspected RA. Anti-CCPwas measured by enzyme-linked immunosorbent assay (ELISA) and rheumatoid factor (RF) by nephalometry. The seropositivity with RF and ACCP antibodies were studied in comparison with radiographic changes and joint symptoms which included presence and duration of joint involvement- multiple joints, small joints, symmetric joints, stiffness or swelling of joints.Results: Among the 60 patients, the mean age for RA was found to be 43 years. A higher seropositivity was found among the females. The sensitivity and specificity ofanti-CCPreactivity for the diagnosis of RAwere 38.3 and 100 respectively. Among the symptoms studied, small joint involvement and involvement of multiple joints showed a positive association with serologically positive individuals. Patients with high anti-CCP antibody titres showed higher RF titres and severe radiographic erosions.Conclusion: Anti CCP antibodies are a highly specific for rheumatoid arthritis. A combined diagnosis using both high titers ofanti-CCPantibodiesand a positive RF test markedly improvesRAdiagnostic specificity. ACCP antibody detection helps in early diagnosis as well as detection of progressive joint damage.

Attainment and characteristics of clinical remission according to the new ACR-EULAR criteria in abatacept-treated patients with early rheumatoid arthritis: new analyses from the Abatacept study to Gauge Remission and joint damage progression in methotrexate (MTX)-naive patients with Early Erosive rheumatoid arthritis (AGREE).

IntroductionThis study evaluated various remission criteria in abatacept plus methotrexate (MTX)-treated patients with early rheumatoid arthritis (RA). We aimed to investigate the time to, and sustainability of, remission, and to evaluate the relationship between remission, function and structure.MethodsPost hoc analyses were performed from the 12-month, double-blind period of the Abatacept study to Gauge Remission and joint damage progression in methotrexate (MTX)-naive patients with Early Erosive rheumatoid arthritis (AGREE) in patients with early RA (≤2 years) and poor prognostic factors, comparing abatacept plus MTX (n = 210) versus MTX alone (n = 209).ResultsAt month 12, Disease Activity Score 28, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index and Boolean remission rates were, for abatacept plus MTX versus MTX alone: 47.6 % versus 27.3 %, 33.3 % versus 12.4 %, 34.3 % versus 16.3 %, and 23.8 % versus 5.7 %, respectively. Cumulative probability demonstrated higher proportions achieving first remission and first sustained remission for abatacept plus MTX versus MTX alone (e.g., 23.3 % [95 % confidence interval (CI): 17.6, 29.1] vs 12.9 % [8.4, 17.5] for first SDAI remission over 0–6 months). For patients in SDAI remission at month 3, mean Health Assessment Questionnaire-Disability Index at month 12 was 0.20 versus 0.50 for abatacept plus MTX versus MTX alone. Mean changes in radiographic score from baseline to month 12 were minimal for patients in SDAI remission at month 3 in both groups, while less structural damage progression was seen, 0.75 versus 1.35, respectively, for abatacept plus MTX versus MTX alone for patients with moderate/high disease activity at month 3 (adjusted mean treatment difference: −0.60 [95 % CI: −1.11, −0.09; P < 0.05]).ConclusionsHigh proportions of abatacept plus MTX-treated patients achieved stringent remission criteria. Remission was associated with long-term functional benefit; dissociation was seen between clinical and structural outcomes for abatacept. These findings highlight the impact of reaching stringent remission targets early, on physical function and structural damage, in MTX-naïve biologic-treated patients.Trial registrationClinicalTrials.gov identifier NCT00122382. Registered 19 July 2005.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0671-9) contains supplementary material, which is available to authorized users.