Impact of a magnetic resonance imaging-guided treat-to-target strategy on disease activity and progression in patients with rheumatoid arthritis (the IMAGINE-RA trial): study protocol for a randomized controlled trial MR imaging findings in hands in early rheumatoid arthritis: comparison with those in systemic lupus erythematosus and primary Sjögren syndrome. The progression of erosion and joint space narrowing scores in rheumatoid arthritis during the first twenty-five years of disease. A simple algorithm to predict the development of radiological erosions in patients with early rheumatoid arthritis: prospective cohort study Development of radiographic damage during the first 5-6 yr of rheumatoid arthritis. A prospective follow-up study of a Swedish cohort. A prediction rule for disease outcome in patients with undifferentiated arthritis using magnetic resonance imaging of the wrists and finger joints and serologic autoantibodies. Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial) Low-Dose Prednisone Therapy for Patients with Early Active Rheumatoid Arthritis: Clinical Efficacy, Disease-Modifying Properties, and Side Effects: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. The influence of HLA-DRB1 alleles and rheumatoid factor on disease outcome in an inception cohort of patients with early inflammatory arthritis. Elucidation of the relationship between synovitis and bone damage: a randomized magnetic resonance imaging study of individual joints in patients with early rheumatoid arthritis. Usefulness of magnetic resonance imaging of the hand versus anticyclic citrullinated peptide antibody testing to confirm the diagnosis of clinically suspected early rheumatoid arthritis in the absence of rheumatoid factor and radiographic erosions. Inflammation and damage in an individual joint predict further damage in that joint in patients with early rheumatoid arthritis. Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis Magnetic Resonance Imaging of the Rheumatic Foot According to the RAMRIS System Is Reliable Bone Marrow Edema Is the Most Specific Finding for Rheumatoid Arthritis (RA) on Noncontrast Magnetic Resonance Imaging of the Hands and Wrists: A Comparison of Patients with RA and Healthy Controls Sustained inhibition of progressive joint damage with rituximab plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a high prevalence of erosions at four months after symptom onset Raised granzyme B levels are associated with erosions in patients with early rheumatoid factor positive rheumatoid arthritis. MR imaging of erosions in interphalangeal joint osteoarthritis: is all osteoarthritis erosive? A prognostic index for erosive changes in the hands, feet, and cervical spines in early rheumatoid arthritis. Cigarette smoking and radiographic progression in rheumatoid arthritis
Background Rheumatoid arthritis ( RA ) is a chronic , progressive joint disease , which frequently leads to irreversible joint deformity and severe functional impairment . Although patients are treated according to existing guidelines and reach clinical remission , erosive progression still occurs . This demonstrates that additional methods for prognostication and monitoring of the disease activity are needed . Bone marrow edema ( BME ) detected by magnetic resonance imaging ( MRI ) has proved to be an independent predictor of subsequent radiographic progression . Guiding the treatment based on the presence/absence of BME may therefore be clinical ly beneficial . We present the design of a r and omized controlled trial ( RCT ) aim ing to evaluate whether an MRI-guided treatment strategy compared to a conventional treatment strategy in anti-CCP-positive erosive RA is better to prevent progression of erosive joint damage and increase the remission rate in patients with low disease activity or clinical remission . Methods / design The study is a non-blinded , multicenter , 2-year RCT with a parallel group design . Two hundred anti-CCP-positive , erosive RA patients characterized by low disease activity or remission , no clinical ly swollen joints and treatment with synthetic disease-modifying antirheumatic drugs ( DMARDs ) will be included . Patients will be r and omized to either a treatment strategy based on conventional laboratory and clinical examinations ( control group ) or a treatment strategy based on conventional laboratory and clinical examinations as well as MRI ( intervention group ) . Treatment is intensified according to a predefined treatment algorithm in case of inflammation defined as a disease activity score ( DAS28 ) > 3.2 and at least one clinical ly swollen joint ( control and intervention groups ) and /or MRI-detected BME ( intervention group only ) . The primary outcome measures are DAS28 remission ( DAS28 < 2.6 ) and radiographic progression ( Sharp/vdHeijde score ) . Discussion The perspectives , strengths and weaknesses of this study are discussed . This study has been approved by The Regional Scientific Ethical Committees for Southern Denmark , S-20110109 . Dissemination will occur through presentations and publication in international peer- review ed journals . Trial registration The study is registered in http://www . Clinical Trials.gov identifier : NCT01656278 ( 5 July 2012 PURPOSE To evaluate prospect ively the use of magnetic resonance ( MR ) imaging for differentiating true rheumatoid arthritis ( RA ) from systemic lupus erythematosus ( SLE ) or primary Sjögren syndrome in patients who have inflammatory polyarthralgia of the h and s but no radiographic evidence of RA . MATERIAL S AND METHODS This study had institutional review board approval , and patient informed consent was obtained . Twenty-eight patients ( 16 female and 12 male patients ; mean age , 42 years ) with early RA and 19 patients ( 18 female and one male patient ; mean age , 46 years ) with SLE ( n = 14 ) or primary Sjögren syndrome ( n = 5 ) underwent MR imaging of both h and s.  All patients had inflammatory polyarthralgia of the h and s and no evidence of erosive changes on radiographs . Coronal T2-weighted short inversion time inversion-recovery , transverse T1-weighted spin-echo , transverse fat-suppressed gadolinium-enhanced T1-weighted spin-echo , and transverse gadolinium-enhanced three-dimensional gradient-echo MR images were obtained . The following MR imaging variables were assessed in the wrist and nonthumb metacarpophalangeal joints : synovitis , bone lesions ( erosion , defect , and edema ) , and tenosynovitis . Synovitis and bone lesions were scored with the OMERACT RA-MRI scoring system . Findings in patients with RA and those without RA were compared by means of Mann-Whitney , chi2 , and Fisher exact tests . RESULTS The only significant difference between the two groups in terms of individual scores for synovitis , bone lesions , and tenosynovitis was the more frequent presence of tenosynovitis of the right fourth extensor tendon in patients without RA ( P = .04 ) . There were no significant differences between patients with RA and those without RA in terms of global scores for synovitis , bone lesions , and tenosynovitis . However , bone marrow edema in the metacarpophalangeal joints was seen more frequently in patients with RA ( P < .001 ) . CONCLUSION It may be impossible to distinguish between patients with early RA and those without RA ( ie , those with SLE or primary Sjögren syndrome ) by means of MR imaging Erosions and cartilage destruction are nearly universal features in peripheral joints that have been chronically affected by rheumatoid arthritis .  Scoring methods to measure the extent of these abnormalities in h and s and wrists have been developed and have been thoroughly tested in several studies to establish their reproducibility . In this study , we utilized one of these scoring methods to examine the progression of radiologic damage as related to duration of disease . Two hundred ninety-two patients from 3 different participating centers in the Arthritis , Rheumatism , and Aging Medical Information System were included . Six hundred fifty films of the h and s and wrists , obtained from 210 patients , were scored for  erosions and joint space narrowing . The average annual rate of progression of the total radiologic score , which sums erosion and joint space abnormalities and has a maximum possible score of 314 , was approximately 4 units per year over the first 25 years after onset ; this progression was more rapid in the earlier years of disease and slightly slower in the later years . Data were insufficient to accurately determine the progression rate in disease of more than 25 years duration Abstract Objective : To produce a practical algorithm to predict which patients with early rheumatoid arthritis will develop radiological erosions . Design : Primary care based prospect i ve cohort study . Setting : All general practice s in the Norwich Health Authority , Norfolk Subjects : 175 patients notified to the Norfolk Arthritis Register were visited by a metrologist soon after they had presented to their general practitioners with inflammatory polyarthritis , and again after a further 12 months . All the patients satisfied the American Rheumatism Association 's 1987 criteria for rheumatoid arthritis and were seen by a metrologist within six months of the onset of symptoms . The study population was r and omly split into a prediction sample ( n = 105 ) for generating the algorithm and a validation sample ( n = 70 ) for testing it . Main outcome measures : Predictor variables measured at baseline included rheumatoid factor status , swelling of specific joint areas , duration of morning stiffness , nodules , disability score , age , sex , and disease duration when the patient first presented . The outcome variable was the presence of radiological erosions in the h and s or feet , or both , after 12 months . Results : A simple algorithm based on a combination of three variables — a positive rheumatoid factor test , swelling of at least two large joints , and a disease duration of more than three months — was best able to predict erosions . When the accuracy of this algorithm was tested with the validation sample , the erosion status of 79 % of patients was predicted correctly . Conclusions : A simple algorithm based on three easily measured items of information can predict which patients are at high risk and which are at low risk of developing radiological erosions The objective of this study was to describe the development of radiographic damage in patients with RA and to search for predictors of radiographic progression over 5 yr . One hundred and thirteen patients , 75 female and 38 male , mean age 53 yr , with definite RA and mean disease duration of 11.4 months , were followed prospect ively for 5 yr at an out-patient clinic .  Radiographs of the h and s and feet were performed annually , and evaluated according to Larsen . The predictive value of demographic , clinical and laboratory variables at study start was evaluated . A stepwise logistic regression model was applied . We found that radiological joint damage occurred early and was significantly progressive during the 5 study years . The rate of progression was most prominent during the first 2 yr . At study start , 53 % of the patients had no detectable erosions , but only 11 % remained non-erosive . Twenty-six per cent of the patients with the initial presence of erosions did not progress substantially and needed no aggressive therapy . High joint damage progression during the first year , female gender and high baseline ESR could predict 57 % of the patients with high total radiographic progression . Age , disease duration , rheumatoid factor , genetic factors , active joint count and the presence of erosions at study start had no predictive value OBJECTIVE To evaluate whether magnetic resonance imaging ( MRI ) of the wrists and finger joints and an analysis of serologic autoantibodies are clinical ly meaningful for the subsequent development of rheumatoid arthritis ( RA ) in patients with undifferentiated arthritis ( UA ) . METHODS A total of 129 patients with UA , a disease status formally confirmed by a rheumatologist over a period of at least 1 year , were included .  Gadolinium-diethylenetriamine-enhanced MRI of both wrists and finger joints and serologic variables were examined upon admission to our Early Arthritis Clinic at Nagasaki University . After a prospect i ve followup of 1 year , a predictive value for the development of RA was determined for each patient . RESULTS The subjects were evaluated for their positive or negative status with respect to 3 objective measures at study entry : anti-cyclic citrullinated peptide ( anti-CCP ) antibodies and /or IgM-rheumatoid factor , MRI-proven symmetric synovitis , and MRI-proven bone edema and /or bone erosion . The patients who were positive for at least 2 of these measures progressed to RA at 1 year with a 79.7 % positive predictive value ( PPV ) , 63.0 % negative predictive value , 75.9 % specificity , 68.0 % sensitivity , and 71.3 % accuracy . Furthermore , in 22 UA patients positive for both anti-CCP antibodies and MRI-proven bone edema who were considered to have progressed to RA at 1 year , the PPV was increased to 100 % . A close correlation was found between the present rule and that established in the Leiden Early Arthritis Cohort . CONCLUSION MRI-proven early joint damage in conjunction with serologic autoantibodies is efficient in predicting progression from UA to RA . This method can be used to identify patients who would benefit from early treatment with disease-modifying antirheumatic drugs Background Several agents provide treatment for established rheumatoid arthritis ( RA ) , but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis ( UA ) or very early RA . Objective To determine the impact of T-cell costimulation modulation in patients with UA or very early RA . Methods In this double-blind , phase II , placebocontrolled , 2-year study , anti-cyclic citrullinated peptide (CCP)2-positive patients with UA ( not fulfilling the ACR criteria for RA ) and clinical synovitis of two or more joints were r and omised to  abatacept  ( ∼10 mg/kg ) or placebo for 6 months ; the study drug was then terminated . The primary end point was development of RA ( by ACR criteria ) at year 1 . Patients were monitored by radiography , MRI , CCP2 , rheumatoid factor and 28 joint count Disease Activity Score ( DAS28 ) over 2 years . Results At year 1 , 12/26 ( 46 % ) abatacept-treated versus 16/24 ( 67 % ) placebo-treated patients developed RA ( difference ( 95 % CI ) −20.5 % ( −47.4 % to 7.8 % ) ) . Adjusted mean changes from baseline to year 1 in Genant-modified Sharp radiographic scores for abatacepttreated versus placebo-treated patients , respectively , were 0 versus 1.1 for total score , and 0 versus 0.9 for erosion score . Mean changes from baseline to year 1 in MRI erosion , osteitis and synovitis scores were 0 , 0.2 and 0.2 , respectively , versus 5.0 , 6.7 and 2.3 in the abatacept versus placebo groups . Safety was comparable between groups ; serious adverse events occurred in one patient ( 3.6 % ) in each group . Conclusion Abatacept delayed progression of UA/very early RA in some patients . An impact on radiographic and MRI inhibition was seen , which was maintained for 6 months after treatment stopped . This suggests that it is possible to alter the progression of RA by modulating T-cell responses at a very early stage of disease . Trial registration number NCT00124449 Drug treatment for rheumatoid arthritis usually consists of a combination of a nonsteroidal anti-inflammatory drug ( NSAID ) and a disease-modifying antirheumatic drug ( for example , sulfasalazine , methotrexate , gold salt , or a combination ) . New biological agents , such as tumor necrosis factor- blocking agents and interleukin-1 receptor antagonists , appear promising ( 1 , 2 ) . Glucocorticoids have had a special place in the treatment of rheumatoid arthritis since the publication of the report by Hench and coworkers showing that cortisone dramatically alleviated the symptoms of rheumatoid arthritis by inhibiting inflammation ( 3 ) . This period of enthusiasm in the 1950s was followed by a long period in which glucocorticoids were applied cautiously for rheumatoid arthritis because of their many side effects and the recognition that inhibition of inflammation is not necessarily associated with retardation of joint damage ( 4 ) . Ongoing research on glucocorticoids in rheumatoid arthritis focused on both inflammation and joint damage . Some recent studies showed that glucocorticoids reduced the progression of joint damage when added to therapy with disease-modifying antirheumatic drugs . These findings suggested that glucocorticoids might also have disease-modifying properties . If this could be confirmed , glucocorticoids might be used more often , especially since potential serious adverse effects of glucocorticoid therapy are more easily managed today ( 5 ) . Secondary osteoporosis is inhibited by potent bisphosphonates , and gastrointestinal complications of glucocorticoid therapy , especially in combination with NSAIDs , can be reduced by misoprostol , proton-pump inhibitors , or cyclooxygenase-2 selective NSAIDs . As yet , disease-modifying properties of low-dose glucocorticoids as monotherapy for patients with early rheumatoid arthritis have not been investigated . The aim of our study was to investigate the clinical efficacy , disease-modifying properties , and side effects of low-dose glucocorticoids as monotherapy for previously untreated patients with early active rheumatoid arthritis . Methods Patients From October 1992 through October 1995 , all consecutive out patients at the rheumatology departments of the Deventer and Zutphen Hospitals , the Netherl and s , who were at least 18 years of age and had early previously untreated rheumatoid arthritis ( disease duration < 1 year ) that satisfied classification criteria were invited to participate in the study [ 6 ] . To be included , patients had to have active disease , which was defined as the presence of at least two of the following three criteria : 1 ) early-morning stiffness lasting 30 minutes or longer , 2 ) 28-joint score for tenderness and 28-joint score for swelling of 3 or more , and 3 ) Westergren erythrocyte sedimentation rate of 28 mm or higher after 1 hour ( 7 , 8) . Exclusion criteria were contraindications to prednisone  or NSAIDs  , active gastrointestinal problems , serious complicating diseases , severe hypertension , hemorrhagic diathesis , treatment with cytotoxic or immunosuppressive drugs , alcohol or drug abuse , and psychiatric or mental problems . Informed consent was obtained from all patients before participation . Of the 118 eligible patients , 37 declined to participate ( Figure 1 ) . Figure 1 . Trial profile . Intervention Pharmacy personnel at Deventer Hospital used a computer-generated r and omization procedure to r and omly assign the 81 participating patients , in blocks of 10 , to one of two treatment groups . One group received two tablets of prednisone , 5 mg , once daily at breakfast , and one group received placebo . The pharmacology department at Deventer Hospital prepared and labeled the prednisone and placebo tablets , which were identical in shape and color , and distributed them to patients in unlabeled boxes . Only the pharmacist could access the allocation table . Both groups of patients received 500 mg of elementary calcium in the evening . The code of r and omization was broken after 2 years of treatment , and the prednisone dosage was tapered . Surplus tablets of the study medication were counted at every visit , and adherence was satisfactory ( 96 % ) . Use of NSAIDs  was not regulated . Local glucocorticoid injections were permitted only when absolutely necessary . Physical therapy and additional use of paracetamol were allowed . After 6 months , sulfasalazine ( 2 g/d ) could be prescribed as rescue medication . The decision to add sulfasalazine was made on clinical grounds ( activity of rheumatoid arthritis ) . Design and Setting The ethics committees of the University Medical Center Utrecht and the Deventer and Zutphen Hospitals approved the trial . The study was considered ethically acceptable when it was design ed ( 19891991 ) ; later , however , it became clear that irreversible joint damage is an early feature of rheumatoid arthritis . With our present knowledge , it would probably be considered unethical to compare the effects of prednisone and placebo in patients who did not receive a disease-modifying antirheumatic drug for at least 6 months . In our study , sulfasalazine could be prescribed as rescue medication only after 6 months to avoid obscuring the effects of prednisone monotherapy . Measurements All clinical outcome measurements , except those for disability and radiologic outcomes , were performed at baseline and every 3 months . Disability , which was assessed with the Health Assessment Question naire , and radiologic outcomes were measured every 6 months . Early-morning stiffness was recorded in minutes ( maximum , 720 minutes ) . Morning pain and general well-being were assessed on a horizontal visual analogue scale ranging from 0 to 100 mm , with 0 representing the best score ( no problems ) and 100 representing the worst score . Swelling and tenderness were assessed with the 28-joint score ( 7 , 8) . Grip strength was measured in kPa with a vigorimeter ( range , 0 to 200 kPa ) ; the mean of three measurements was calculated for each h and . Disability was assessed with a vali date d Dutch version of the Health Assessment Question naire ( Vragenlijst Dagelijks Functioneren ) ( 9 ) , which had a range of 0 to 3 ( 0 represented the best score [ no problems ] , and 3 represented the worst score ) . Serum C-reactive protein level was measured in mg/L. To investigate the possible sparing effect of the trial medication , we recorded the use of NSAIDs and analgesics , the frequency of intra-articular corticosteroid injections , and the use of physiotherapy . The patients recorded the use of NSAIDs , analgesics  , and physical therapy in st and ardized patient diaries . To calculate the use of NSAIDs and to compare different NSAIDs , we arbitrarily chose naproxen as a reference . One thous and mg of naproxen was defined as 1 unit and was considered to be approximately equivalent to 600 mg of azapropazone , 100 mg of diclofenac , 200 mg of flurbiprofen , 1600 mg of ibuprofen , 100 mg of indomethacin , 200 mg of ketoprofen , 15 mg of meloxicam , 1000 mg of nabumetone , 20 mg of piroxicam , and 600 mg of tiaprofenic acid . Every 3 months , the first author recorded use of intra-articular corticosteroid injections . Radiologic outcome measures were erosions , joint space narrowing , and the total score for both ( range , 0 to 448 ) . The total score is the sum of the erosions and narrowing scores in 44 joints in the h and s and feet , assessed on plain radiography and scored with the van der Heijde modification of the Sharp method ( 10 , 11 ) . Radiologic outcome measures also included the number of patients with erosive disease in each group and the number of radiologically affected joints per patient . Radiographs were taken at entry and every 6 months . An assistant prepared the radiographs to be read , and all identifying patient data on the radiographs were concealed from the readers . The readers had no knowledge of patient identity when they scored the radiographs . Radiographs were read in r and om patient order and were scored for each patient in temporal order . Scoring in temporal order clearly has advantages , as a comparative study has shown ( 11 ) . However , with this method , scores can either be stable or increase ; a decrease ( indicating improvement ) is not possible . The first author and an independent radiologist viewed all available radiographs  at one center . When the readers ' total scores for individual cases differed by 25 % or more , agreement was reached through discussion . Joint damage was defined as a score that exceeded 0 . To correct for possible differences between the two treatment groups in the number of patients who developed little or no joint damage , we also analyzed data only from patients who developed joint damage . Furthermore , radiologic damage was also analyzed with a cutoff point of 4 modified Sharp units . A score of 0 to 3 was interpreted as no damage , and scores of 4 or greater were interpreted as joint damage . This cutoff point seems to reflect clinical ly relevant change ( 12 ) and was also used in our study to define erosive rheumatoid arthritis . At the start of the study and every 3 months for 2 years , st and ardized lists were used to document adverse effects . We noted the occurrence of infections and the use of antibiotics ; the latter was checked at the patient 's pharmacy . For hypertension , the first author used a single device to measure blood pressure in mm Hg . For steroid diabetes , serum glucose level was measured in mmol/L. Hyperglycemia was defined according to the World Health Organization st and ard : postpr and ial , a glucose level of at least 11.0 mmol/L ( 198 mg/dL ) , and fasting , at least 6.6 mmol/L ( 119 mg/dL ) . Urinary glucose level was measured by using a semiquantitative method ( dipstick ) . A value less than 2.7 mmol/L ( 49 mg/dL ) was considered negative , a value of 2.7 to 5.5 mmol/L ( 50 to 99 mg/dL ) was considered a trace , a value of 5.6 to 16.6 mmol/L ( 100 to 299 mg/dL ) was considered 1 + , a value of 16.7 to 54.9 mmol/L ( 300 to 989 mg/dL ) was considered 2 + , and a value of 55 mmol/L or greater ( 990 mg/dL ) was considered 3 + . To assess weight gain , OBJECTIVE RANKL is essential for osteoclast development , activation , and survival . Denosumab is a fully human monoclonal IgG2 antibody that binds RANKL , inhibiting its activity . The aim of this multicenter , r and omized , double-blind , placebo-controlled , phase II study was to evaluate the effects of denosumab on structural damage in patients with rheumatoid arthritis ( RA ) receiving methotrexate treatment . METHODS RA patients received subcutaneous placebo ( n = 75 ) , denosumab 60 mg ( n = 71 ) , or denosumab 180 mg ( n = 72 ) injections every 6 months for 12 months . The primary end point was the change from baseline in the magnetic resonance imaging ( MRI ) erosion score at 6 months . RESULTS At 6 months , the increase in the MRI erosion score from baseline was lower in the 60-mg denosumab group ( mean change 0.13 ; P = 0.118 ) and significantly lower in the 180-mg denosumab group ( mean change 0.06 ; P = 0.007 ) than in the placebo group ( mean change 1.75 ) . A significant difference in the modified Sharp erosion score was observed as early as 6 months in the 180-mg denosumab group ( P = 0.019 ) as compared with placebo , and at 12 months , both the 60-mg ( P = 0.012 ) and the 180-mg ( P = 0.007 ) denosumab groups were significantly different from the placebo group . Denosumab caused sustained suppression of markers of bone turnover . There was no evidence of an effect of denosumab on joint space narrowing or on measures of RA disease activity . Rates of adverse events were comparable between the denosumab and placebo groups . CONCLUSION Addition of twice-yearly injections of denosumab to ongoing methotrexate treatment inhibited structural damage in patients with RA for up to 12 months , with no increase in the rates of adverse events as compared with placebo BACKGROUND Etanercept , which blocks the action of tumor necrosis factor , reduces disease activity in patients with long-st and ing rheumatoid arthritis . Its efficacy in reducing disease activity and preventing joint damage in patients with active early rheumatoid arthritis is unknown . METHODS We treated 632 patients with early rheumatoid arthritis with either twice-weekly subcutaneous etanercept  ( 10 or 25 mg ) or weekly  oral methotrexate ( mean , 19 mg per week ) for 12 months . Clinical response was defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology . Bone erosion and joint-space narrowing were measured radiographically and scored with use of the Sharp scale . On this scale , an increase of 1 point represents one new erosion or minimal narrowing . RESULTS As compared with patients who received methotrexate , patients who received the 25-mg dose of etanercept had a more rapid rate of improvement , with significantly more patients having 20 percent , 50 percent , and 70 percent improvement in disease activity during the first six months ( P<0.05 ) . The mean increase in the erosion score during the first 6 months was 0.30 in the group assigned to receive 25 mg of etanercept and 0.68 in the methotrexate group ( P= 0.001 ) , and the respective increases during the first 12 months were 0.47 and 1.03 ( P=0.002 ) . Among patients who received the 25-mg dose of etanercept , 72 percent had no increase in the erosion score , as compared with 60 percent of patients in the methotrexate group ( P=0.007 ) . This group of patients also had fewer adverse events ( P=0.02 ) and fewer infections ( P= 0.006 ) than the group that was treated with methotrexate . CONCLUSIONS As compared with oral methotrexate , subcutaneous [ corrected ] etanercept acted more rapidly to decrease symptoms and slow joint damage in patients with early active rheumatoid arthritis OBJECTIVE There are conflicting data concerning the role of HLA-DRB1 alleles in disease outcome in early rheumatoid arthritis . The exact role of these alleles in short-term outcome is determined in this large , prospect i ve , population -based study . METHODS We recruited 532 patients with inflammatory polyarthritis from the Norfolk Arthritis Register and typed  their sera for HLA-DRB1 alleles using polymerase chain reaction-based methods . Disease outcome was assessed at 2 years in terms of persistent joint inflammation , functional disability , and radiologic erosions . Results are expressed as risk ratios ( RR ) with 95 % confidence intervals ( 95 % CI ) . RESULTS There was no influence of HLA-DRB1 alleles , in any combination , on the likelihood of disease persistence , and only a modest effect on functional disability ( Health Assessment Question naire score > or = 1 ) . The most obvious effect was on the development of erosions ( RR 1.9 , 95 % CI 1.4 - 2.6 for those who carried at least 1 DRB1 shared epitope [ SE ] allele ) , with slightly greater effects for those who were homozygous for SE-bearing alleles ( RR 2.5 , 95 % CI 1.8 - 3.6 ) . This effect of HLA-DRB1 was restricted to patients whose sera were negative for rheumatoid factor . Among patients with erosions , HLA-DRB1 had no influence on the severity of radiologic damage ( defined as the number of eroded joints , or total Larsen score ) . CONCLUSION These data do not support routine HLA-DRB1 screening of patients with early arthritis to identify those at risk for subsequent severe disease OBJECTIVE To simultaneously image bone and synovium in the individual joints characteristically involved in early rheumatoid arthritis ( RA ) . METHODS Forty patients with early , untreated RA underwent gadolinium-enhanced magnetic resonance imaging ( MRI ) of the second through fifth metacarpophalangeal joints of the dominant h and at presentation , 3 months , and 12 months . In the first phase ( 0 - 3 months ) , patients were r and omized to receive either methotrexate alone ( MTX ) or MTX and intraarticular corticosteroids ( MTX + IAST ) into all joints with clinical ly active RA . The MTX-alone group received no further corticosteroids until the second phase ( 3 - 12 months ) , when both groups received st and ard therapy . RESULTS In the first phase , MTX + IAST reduced synovitis scores more than MTX alone . There were significantly fewer joints with new erosions on MRI in the former group compared with the latter . During the second phase , the synovitis scores were equivalent and a similar number of joints in each group showed new erosions on MRI . In both phases , there was a close correlation between the degree of synovitis and the number of new erosions , with the area under the curve for MRI synovitis the only significant predictor of bone damage progression . In individual joints , there was a threshold effect on new bone damage related to the level of synovitis ; no erosions occurred in joints without synovitis . CONCLUSION In early RA , synovitis appears to be the primary abnormality , and bone damage occurs in proportion to the level of synovitis but not in its absence . In the treatment of patients with RA , outcome measures and therapies should focus on synovitis OBJECTIVE The diagnosis of rheumatoid arthritis ( RA ) is sometimes difficult to establish early in the disease process , particularly in the absence of its classic hallmarks . Our aim was to compare the practical usefulness of magnetic resonance imaging ( MRI ) of the h and versus anticyclic citrullinated peptide ( anti-CCP ) antibody testing to confirm the diagnosis of clinical ly suspected RA in the absence of rheumatoid factor ( RF ) and radiographic erosions . METHODS We prospect ively included patients with early inflammatory arthritis and strong clinical suspicion of RA , in whom initial complementary tests ( RF and radiographs of h and s , wrists , and feet ) did not provide unequivocal confirmation of the diagnosis . In all patients , anti-CCP antibodies were assessed and contrast-enhanced MRI of the most affected h and was performed according to a specifically design ed protocol . The MRI criterion for the diagnosis of RA was either the presence of synovitis with bone erosions or bone marrow edema , which is currently considered to be a forerunner of erosions . RESULTS In the 40 patients ( 28 women ) , the mean age at diagnosis was 54 + /- 6 years and the median duration of symptoms was 4 + /- 2.6 months ( range 1.5 to 12 ) . Final diagnoses at 1-year follow-up were RA in 31 patients , undifferentiated arthritis in 7 ( 5 self-limiting ) , and psoriatic arthropathy ( PsA ) and antisynthetase syndrome in 1 patient each . Anti-CCP antibodies were positive only in 7 patients , all of whom were finally diagnosed with RA . The prevalence of anti-CCP positivity in our series of seronegative RA patients was thus 23 % ( 7/31 ) ; in these patients the anti-CCP antibodies had a specificity of 100 % ( 95 % CI : 71.7 to 100 ) and sensitivity of 23 % ( 95 % CI : 9.6 to 41.1 ) . Use of the MRI criterion led to the correct diagnosis in 100 % of patients with RA and to false-positive results ( 1 with PsA and 1 with antisynthetase syndrome ) . The MRI criterion had a specificity of 78 % ( 95 % CI : 40.0 to 97.2 ) and sensitivity of 100 % ( 95 % CI : 90.8 to 100 ) for identification of seronegative RA . CONCLUSION Although the tests are not mutually exclusive , in our experience MRI is more helpful than anti-CCP antibody determination in confirming the diagnosis of clinical ly suspected early RA in patients in whom the diagnosis can not be confirmed using conventional methods UNLABELLED OBJECTIVE ; Several factors predict joint damage in early rheumatoid arthritis ( RA ) . In the context of a trial in early RA , we studied the relationship between clinical signs in individual joints and their propensity to develop progressive damage . METHODS The COBRA ( Combinatietherapie Bij Reumatoide Artritis ) multicenter trial compared the efficacy of prednisolone , methotrexate , and sulfasalazine against sulfasalazine alone in 155 patients with early RA . Two blinded observers interpreted radiographs in sequence ( using the Sharp/Van der Heijde scoring system ) ; in each center , one blinded observer performed clinical assessment s every 3 months . The current analysis is based on clinical and radiologic data of the individual metacarpophalangeal ( MCP ) and proximal interphalangeal ( PIP ) joints of 135 patients . Conditional stepwise logistic regression analyzed the relationship between damage ( progression ) and clinical signs at baseline and followup for each of these joints individually in each patient . RESULTS Combination therapy strongly retarded the progression of damage . Progression was stronger in patients with rheumatoid factor , HLA-DR4 , and high levels of disease activity at baseline . At baseline , 6 % of the MCP and PIP joints showed damage ; after 1 year , disease had progressed in 10 % of these joints . Baseline damage , swelling , or pain in a joint independently and strongly predicted the progression of damage in that joint ( P < 0.001 ) . Each additional point in the swelling score ( range 0 - 2 ) tripled the risk for subsequent progression . Each additional point on the Sharp scale ( range 0 - 8 per joint ) and each additional point on the pain scale ( range 0 - 3 ) doubled the risk . The mean pain and swelling scores over the year were even stronger predictors of damage . CONCLUSION Local expression of early RA disease activity , both at baseline and at 1-year followup , is strongly related to progression of damage in the individual joint Background : Early treatment prevents progression of joint damage in rheumatoid arthritis ( RA ) , but diagnosis in early disease is impeded by lack of appropriate diagnostic criteria . Objective : To study the value of rheumatoid factor ( RF ) , anti-cyclic citrullinated peptide autoantibodies ( anti-CCP ) , and anti-RA33 autoantibodies for diagnosis of RA and prediction of outcome in patients with very early arthritis . Methods : The prospect i ve follow up inception cohort included 200 patients with very early ( <3 months ) inflammatory joint disease .  Autoantibodies  were measured at baseline and analysed in a tree based model which aim ed at determining the added diagnostic value of testing for anti-CCP and anti-RA33 as compared with RF alone . Results : RA was diagnosed in 102 patients , while 98 developed other inflammatory arthropathies . Receiver operator curve analysis showed an optimum cut off level for RF at 50 U/ml , above which anti-CCP and anti-RA33 had no additional diagnostic value . Remarkably , RF ⩾50 U/ml and anti-CCP showed similar sensitivity and high specificity for RA , but overlapped considerably . Anti-RA33 was less specific and did not correlate with RF or anti-CCP . Among patients with RA , 72 % showed at least one of these three autoantibodies , compared with 15 % of non-RA patients . RF ⩾50 U/ml and anti-CCP were predictors of erosive disease , whereas anti-RA33 was associated with mild disease . Conclusions : Stepwise autoantibody testing in early inflammatory joint disease , starting with RF , followed by anti-CCP ( in patients with RF < 50 U/ml ) , and finally anti-RA33 , should be used as a sensitive and effective strategy for distinguishing patients with RA at high risk for poor outcome Objective . In rheumatology , magnetic resonance imaging ( MRI ) is predominantly applied in the assessment and outcome measurement of rheumatoid arthritis ( RA ) in h and s and wrists , leading to the development of the RAMRIS ( RA-MRI-Scoring ) system . It was initiated by the Outcome Measures in Rheumatoid Arthritis Clinical Trials ( OMERACT ) . The RAMRIS system has not been applied widely in the measurement of feet . We investigated the interreader and intrareader agreement of the RAMRIS scoring system in the assessment of feet in RA . Methods . Twenty-nine patients with RA who had radiological damage and /or arthritis underwent MRI .  Two experienced readers independently read both complete sets . One reader read 6 r and om sets after the initial session , in order to assess the intrareader agreement . For evaluation of the intrareader and interreader reliability , quadratic-weighted κ scores were calculated per joint and lesion . Results . For the forefeet , interreader scores were excellent , ranging from 0.77 ( bone edema ) to 0.95 ( bone erosion ) . Hindfoot interreader agreement scores were highest for erosion ( 0.90 ) and synovitis global score ( 0.88 ) , but edema and synovial thickness agreement were also acceptable ( 0.83 and 0.86 ) . Intrareader scores were on the whole slightly lower , but excellent . Conclusion . Reliability ( interreader and intrareader agreement ) in the assessment of the rheumatoid foot according to the RAMRIS method is excellent Objective . To evaluate the sensitivity and specificity of magnetic resonance imaging ( MRI ) in detecting erosions , bone edema , and synovitis in the metacarpophalangeal and wrist joints for rheumatoid arthritis ( RA ) . Methods . MRI scans of bilateral h and s and wrists of 40 healthy subjects and 40 RA patients were performed using 0.2 T extremity-MRI and read blindly using a modified RA MRI ( RAMRIS ) system ( no contrast injection , imaging in 1 plane only ) . To determine interreader reliability , images of 10 r and omly selected subjects were read independently by a musculoskeletal radiologist . Results . A total of 3360 bones were evaluated . Patients with RA had significantly more erosions as well as higher scores for bone edema and synovitis than healthy subjects . Age had a significant effect on the number of erosions in both groups . However , when disease duration was factored in , age became insignificant in RA patients . Erosion number correlated with positive rheumatoid factor and higher C-reactive protein values . The intraclass correlation coefficient between the 2 readers was 0.76 for individual joints and 0.88 for total scores . When having a single erosion was used as a positive test for RA , the sensitivity of this test was 90 % , but the specificity was only 35 % . Presence of bone edema provided 65 % sensitivity and 82.5 % specificity . Eliminating the lunate from scoring for bone edema increased the specificity to 87.5 % while decreasing the sensitivity to 62.5 % . Conclusion . While MRI is a highly sensitive tool for identifying and tracking the progression of erosions , erosions detected by MRI with measures commonly used in a rheumatologist ’s office ( no contrast , imaging in 1 plane ) provide low specificity for RA . Bone marrow edema is the most specific MRI lesion for RA in this setting Background In the IMAGE study , rituximab plus methotrexate ( MTX ) inhibited joint damage and improved clinical outcomes at 1 year in MTX-naïve patients with early active rheumatoid arthritis . Objective The aim of this study was to assess joint damage progression and clinical outcomes over 2 years . Methods Patients ( n=755 ) were r and omised to receive rituximab 2 × 500 mg+MTX , 2 × 1000 mg+MTX or placebo+MTX . The placebo-controlled period continued to week 104 . Two-year end points were defined as secondary or exploratory and included change in total Genant-modified Sharp score ( mTSS ) , total erosion score and joint space narrowing score from baseline to week 104 . Clinical efficacy and physical function end points were also assessed . Results At 2 years , rituximab 2 × 1000 mg+MTX maintained inhibition of progressive joint damage  versus MTX alone ( mTSS change 0.41 vs 1.95 ; p<0.0001 ( 79 % inhibition ) ) , and a higher proportion of patients receiving rituximab 2 × 1000 mg+MTX had no radiographic progression over 2 years compared with those receiving MTX alone ( 57 % vs 37 % ; p<0.0001 ) . Contrary to 1-year results , exploratory analysis of rituximab 2 × 500 mg+MTX at 2 years showed that progressive joint damage was slowed by ∼61 % versus placebo+MTX ( mTSS , exploratory p=0.0041 ) . Improvements in clinical signs and symptoms and physical function seen after 1 year in rituximab-treated patients versus those receiving placebo were maintained at year 2 . Safety profiles were similar between groups . Conclusions Treatment with rituximab 2 × 1000 mg+MTX was associated with sustained improvements in radiographic , clinical and functional outcomes over 2 years . Clinical trials.gov identifier NCT00299104 OBJECTIVES To evaluate the role of magnetic resonance imaging ( MRI ) of the wrist in detecting early joint damage in patients with rheumatoid arthritis ( RA ) . METHODS  MRI was performed on 42 patients with early RA ( median symptom duration of four months ) . Scans were scored separately by two musculoskeletal radiologists using a newly devised scoring system , which was vali date d. MRI findings were compared with plain radiography , clinical measures , and HLA-DRB*01/04 genotyping . RESULTS Interobserver reliability for the overall MRI score was high ( r = 0.81 ) as was intraobserver reliability ( r = 0.94 for observer 1 and 0.81 for observer 2 ) . There was more variation in scoring synovitis ( interobserver reliability : r = 0.74 ) . Erosions were detected in 45 % of scans ( 19 of 42 ) , compared with 15 % of plain radiographs . The most common site for erosions was the capitate ( 39 % ) , for synovitis the ulnar aspect of the radiocarpal joint , and for tendonitis , the extensor carpi ulnaris tendon . The total MRI score and MRI synovitis score correlated most significantly with C reactive protein ( r = 0.40 and 0.42 respectively , p<0.01 ) . The MRI erosion score was highly correlated with MRI bone marrow oedema ( r = 0.83 ) as well as the Ritchie score and disease activity score ( r = 0.32 , p<0.05 ) . HLA-DRB1 * 04 or * 01 ( shared epitope + ve ) was found in 76 % of patients ; 84 % of those with MRI erosions and 69 % of those without ( NS , p = 0.3 ) . CONCLUSIONS A high proportion of RA patients develop MRI erosions very early in their disease , when plain radiography is frequently normal . MRI of the dominant wrist may identify those requiring early aggressive treatment BACKGROUND Raised granzyme B in serum and synovium of patients with rheumatoid arthritis suggests a role for cytotoxic T cells and natural killer cells in the pathogenesis of this disease . OBJECTIVE To evaluate serum granzyme B in patients with early arthritis and correlate it with specific diagnosis and clinical indices of disease severity . METHODS 257 patients with inflammatory arthritis for less than one year ( 46 % rheumatoid arthritis , 17 % spondyloarthropathy , 37 % undifferentiated arthritis ) had a prospect i ve clinical , serological , and radiographic evaluation .  Granzyme B was measured in initial sera by ELISA .  Patients were HLA typed for DR alleles using sequence specific primers . A logistic regression model was used to evaluate the potential prognostic value of serum granzyme B in predicting radiographic erosions after one year of follow up . RESULTS Granzyme B values were similar in rheumatoid arthritis , spondyloarthropathy , and undifferentiated arthritis . Concentrations were higher in rheumatoid factor ( RF ) positive patients than in RF negative patients ( mean ( SD ) : 3.15 ( 0.92 ) v 2.89 ( 0.71 ) pg/ml ; p<0.05 ) . After one year , erosions were present in 30 % of patients in the overall cohort , and in 44 % of patients with rheumatoid arthritis . In the entire cohort , serum granzyme B did not predict erosions independently . However , high granzyme B was an independent predictor of early erosions in patients with RF positive rheumatoid arthritis ( odds ratio = 4.83 ( 95 % confidence interval , 1.13 to 20.59 ) ) ( p<0.05 ) . CONCLUSIONS Granzyme B may be a useful prognostic marker in early rheumatoid arthritis and may provide important clues to the pathogenesis of this disease Objective Erosive osteoarthritis is usually considered as an inflammatory subset of osteoarthritis ( OA ) . However , an inflammatory component is now recognised in all subsets of OA , so this subgroup of erosive or inflammatory OA is more difficult to conceptualise . The aim of this study was to compare routine CR and MRI to investigate erosion numbers and morphology to determine whether h and OA in general is a more erosive disease than previously recognised . Design and methods Fifteen patients with clinical ( OA ) of the small joints of the h and underwent MRI of one of the affected proximal interphalangeal ( PIP ) or distal interphalangeal ( DIP ) joints .  Conventional radiographs ( CR ) of the h and were also obtained . The MR images were review ed by two observers for the presence of central and marginal erosions . The site and morphology of any erosions was recorded . CR images of the same h and joint were scored independently for central and marginal erosions by the same observers . Results There was 100 % agreement between the observers for scoring erosions on CR . Agreement for the MRI scores was also excellent ( kappa = 0.84 ) . MRI detected 37 erosions , of which only 9 were seen on CR . The increase in sensitivity using MRI was much greater for marginal erosions ( 1 detected on CR , 19 on MRI ) than for central erosions ( 8 on CR , 18 on MRI ) . Using MRI 80 % of joints examined showed 1 or more erosions compared with 40 % using CR . If only marginal erosions were considered 80 % of joints were still considered erosive by MRI criteria , but only 1 showed evidence of erosion on CR . Morphologically central erosions appeared to represent areas of subchondral collapse and pressure atrophy . In contrast , marginal erosions resembled those seen in inflammatory arthritides . Conclusion Erosions , and particularly marginal erosions typical of those seen in inflammatory arthritis , are a more common feature of small joint OA than conventional radiographs have previously indicated Clinical and laboratory measurements taken at the onset of rheumatoid arthritis in 149 patients were compared with the severity of radiological changes seen at 3 years in the h and s and feet , and cervical spine . The strongest association with the severity of peripheral radiological damage was rheumatoid factor ( p less than 0.0001 for both the latex titre and RAHA titre ) . Subluxation of the cervical spine was associated only with the presence of HLA-Dw2 ( p less than 0.02 ) and HLA-B7 cross-reacting group ( p less than 0.02 ) . Discriminant function analysis utilizing latex titre , RAHA titre , haemoglobin level , and platelet count predicted the development of erosive or nonerosive disease in 79 % . This method was less successful in predicting the actual severity of erosive damage and was not improved by the addition of HLA data . Radiological outcome in the cervical spine was successfully predicted in 82 % using HLA-Dw2 , HLA-B27 and age of onset of disease . It is concluded that the best predictors of erosive disease were st and ard laboratory features measured at onset , but that more powerful discriminant factors are needed if these are to influence clinical practice . Further prospect i ve studies will establish whether rheumatoid involvement of the cervical spine is an expression of the influence of HLA determinants in this disease Background : Smoking is a well-established environmental risk factor for the development of rheumatoid arthritis ( RA ) . However , it remains unclear whether smoking influences RA disease progression and whether smokers have more radiographic damage progression than non-smokers over time . Objective : To compare the rates of radiographic damage progression in current smokers and non-smokers in a large prospect i ve RA cohort . Methods : The SCQM-RA is a population -based registry monitoring disease activity , radiographic damage and symptoms at regular intervals . All patients in the SCQM-RA data base with sequential plain radiographs were included .  Joint erosions were assessed in 38 h and and foot joints with a vali date d scoring method . The rate of erosion progression was analysed using multivariate longitudinal regression models and adjusted for potential confounders . Results : 2004 RA patients with a mean of 3.6 sequential radiographs and 3.1 years of follow-up were included . The 545 ( 27 % ) current smokers smoked on average 16 cigarettes per day and had a mean past smoking exposure of 20.6 pack-years . Radiographic joint damage progressed at a similar rate in current smokers and non-smokers ( p = 0.26 ) . However , smoking intensity was associated with a significant inverse dose – response ; heavy smokers ( > 1 pack-day ) progressed significantly less than non-smokers or moderate smokers ( p<0.001 ) . Conclusion : Radiographic joint damage progressed at an equivalent rate in smokers and non-smokers . Furthermore , a significant trend was observed for reduced radiographic progression and generally more favourable functional scores among heavy smokers , suggesting that cigarette smoke does not accelerate RA disease progression
It can be classified according to their configuration , shape , content , and can be described specifically with an anatomical term . “
Rheumatoid arthritis is a chronic inflammatory disease characterized by the development of osseous and cartilaginous damage .
The correct differentiation between a true erosion and other entities — then often called “ pseudoerosions”—is essential to avoid misdiagnosing rheumatoid arthritis and to correctly interpret the progress of the disease .
The aims of this systematic review were as follows : to create a definition and delineation of the term “ pseudoerosion ” , to point out morphological pitfalls in the interpretation of images , and to report on difficulties arising from choosing different imaging modalities .