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ID PMID Title PublicationDate abstract
18700876 Inhibitory NKG2A and activating NKG2D and NKG2C natural killer cell receptor genes: suscep 2008 Oct The inhibitory (NKG2A) and activating (NKG2D and NKG2C) natural killer (NK) cell receptors are expressed on a subset of NK and T cells. They regulate the innate and adaptive immune systems related to cytotoxicity and cytokine production that are involved in the pathogenesis of rheumatoid arthritis (RA). The role of inhibitory and activating NK cell receptor genes might contribute to chronic inflammation and destruction of bone and cartilage in RA. Therefore, we investigated the association of the NKG2A, NKG2C, and NKG2D genotypes with RA. NKG2A (KLRC1) NKG2C (KLRC2), and NKG2D (KLRK1, D12S249E) genes were genotyped in 210 unrelated patients with RA and 298 controls using a polymerase chain reaction-restriction fragment length polymorphism. We further investigated the relationships between the genotypes of each single nucleotide polymorphism and the presence of rheumatoid factor (RF), antinuclear antibody (ANA), and bony erosions in RA patients. The major NKG2A c.338-90*A/*A, NKG2C102*Ser/*Ser, and NKG2D72*Ala/*Ala genotypes in RA were significantly associated compared with controls [P = 0.013, odds ratio (OR) = 0.6, 95% confidence interval (CI) = 0.44-0.91; P < 0.0001, OR = 2.1, 95% CI = 1.44-2.96; and P = 0.019, OR = 0.6, 95% CI = 0.45-0.93, respectively]. The minor NKG2A c.338-90*G/*G, NKG2C102*Phe/*Phe, and NKG2D72*Thr/*Thr genotypes showed a risk of RA (P = 0.010, OR = 2.0, 95% CI = 1.17-3.54; P < 0.0001, OR = 0.2, 95% CI = 0.12-0.48; and P = 0.032, OR = 2.3, 95% CI = 1.05-5.01, respectively) compared with controls. No significance was observed between the inhibitory (NKG2A) or activating (NKG2C and NKG2D) receptor genotypes and the presence of RF, ANA, or bony erosions in RA.
17384177 MHC class II expression on myeloid cells inversely correlates with disease progression in 2007 Jun OBJECTIVE: To investigate whether MHC class II expression on myeloid cells of patients with treatment-naive early rheumatoid arthritis (RA) correlates with disease progression. METHODS: Monocytes were isolated by negative selection from the peripheral blood of 15 patients with early RA (disease duration < or =12 months), differentiated to macrophages and analysed for MHC class II expression by flowcytometry. The phenotypical data were correlated with clinical disease progression for up to 45 months. RESULTS: Before treatment was initiated, in vitro differentiated macrophages of 10/15 early RA patients expressed MHC class II comparable with macrophages from healthy controls. In sharp contrast, macrophages of the remaining five patients expressed significantly fewer MHC class II molecules. In contrast to patients with normal levels of myeloid cell MHC class II expression, who developed a smouldering, non-progressive disease, patients with decreased expression of MHC class II on macrophages early in their disease developed a continuously active disease as demonstrated by persistently increased disease activity scores (chi(2) = 4.54, P < 0.02) and progressive bone destructions (chi(2) = 5.66, P < 0.02) despite aggressive therapy. CONCLUSION: The level of myeloid cell MHC class II expression in recent onset RA allows a reliable distinction between patients who develop active and destructive RA and patients with a smouldering, slowly progressive disease.
16542466 Fish oil: what the prescriber needs to know. 2006 There is a general belief among doctors, in part grounded in experience, that patients with arthritis need nonsteroidal anti-inflammatory drugs (NSAIDs). Implicit in this view is that these patients require the symptomatic relief provided by inhibiting synthesis of nociceptive prostaglandin E2, a downstream product of the enzyme cyclo-oxygenase (COX), which is inhibited by NSAIDs. However, the concept of 'safe' NSAIDs has collapsed following a multiplicity of observations establishing increased risk for cardiovascular events associated with NSAID use, especially but not uniquely with the new COX-2-selective NSAIDs. This mandates greater parsimony in the use of these agents. Fish oils contain a natural inhibitor of COX, reduce reliance on NSAIDs, and reduce cardiovascular risk through multiple mechanisms. Fish oil thus warrants consideration as a component of therapy for arthritis, especially rheumatoid arthritis, in which its symptomatic benefits are well established. A major barrier to the therapeutic use of fish oil in inflammatory diseases is ignorance of its mechanism, range of beneficial effects, safety profile, availability of suitable products, effective dose, latency of effects and instructions for administration. This review provides an evidence-based resource for doctors and patients who may choose to prescribe or take fish oil.
18785315 Distribution of myeloid dendritic cells and plasmacytoid dendritic cells in the synovial t 2008 Oct OBJECTIVE: To examine the precise tissue distribution of dendritic cells (DC) and indoleamine 2,3-dioxygenase (IDO)-expressing cells in synovial tissue and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Synovial tissues from 30 patients with RA and 7 with OA were immunohistochemically stained for DC markers. The examined areas were classified into 5 categories based on pathobiological staging and histopathological grading systems. Myeloid DC (mDC) and plasmacytoid DC (pDC) were isolated using positive and negative magnetic sorting systems, respectively, from SF samples (7 patients with RA and 4 with OA) and synovial tissues (3 RA, 4 OA). RESULTS: mDC were mainly observed in lymphoid aggregations. pDC were scattered around perivenular infiltration areas, and small and large lymphoid aggregations in RA. The mDC/pDC ratio increased significantly, with higher grading in RA SF tissues compared to OA synovial tissues (p<0.05). IDO-immunoreactivity was detected in pDC by serial sectioning and staining of RA synovial tissues. CONCLUSION: Our results indicate that mature mDC play a central role in the RA inflammatory process. Although there were fewer pDC than mDC, the presence of IDO-positive pDC suggests a possible tolerance mechanism in RA synovial tissues. However, it is probably modest due to the marked inflammation in RA, in which mDC are dominant.
17055211 Genetic basis of rheumatoid arthritis. 2006 Dec Rheumatoid arthritis (RA) is a clinically heterogeneous condition with a complex aetiology in which environmental and genetic factors are implicated. The contribution of human leukocyte antigen (HLA) genes, particularly the HLA-DRB1 gene, to RA genetic predisposition was the first described, and remains as the best characterised single genetic risk factor contributing to RA. However, it has been estimated that only 30% of the genetic contribution to RA can be attributed to HLA genes and it is suggested that other non-HLA genes may play a relevant role in RA susceptibility. Linkage studies and association studies are the two main strategies used in the investigation of genetic factors contributing to complex genetic traits. In this work we review the progress made in the field of RA genetics, focusing mainly on the contribution of candidate gene association studies to the dissection of RA genetic risk factors.
17050366 Contrast-enhanced dynamic magnetic resonance imaging of finger joints in osteoarthritis an 2006 Oct PURPOSE: To investigate a two-compartment kinetic model applied to the dynamic time course of contrast enhancement as a method to differentiate between finger-joint synovitis in established osteoarthritis (OA) and rheumatoid arthritis (RA). MATERIAL AND METHODS: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of one hand in 19 patients and six healthy volunteers was undertaken. Eight patients had OA of the hand and eleven patients had RA. From the signal intensity curves, the three parameters Kps (endothelial transfer constant), Kep (elimination rate constant from extracellular space back to plasma) and Kel (elimination rate constant from plasma by renal excretion) were calculated. RESULTS: The rate constant Kps showed the best separation between the groups with significantly higher values in the RA group compared to the OA group (P<0.005) and in the OA group compared to the control group (P<0.005). Significantly higher values of Kep were also found in the RA group compared with the OA group (P<0.005). CONCLUSION: DCE-MRI may provide useful information that can help differentiate synovitis in OA from synovitis in RA.
17349293 [Gene therapy for osteoarticular disorders]. 2007 Mar Osteoarticular disorders are the major cause of disability in Europe and North America. It is estimated that rheumatoid arthritis affects 1 % of the population and that more than two third of people over age 55 develop osteoarthritis. Because there are no satisfactory treatments, gene therapy offers a new therapeutic approach. The delivery of cDNA encoding anti-arthritic proteins to articular cells has shown therapeutic efficacy in numerous animal models in vivo. Through the development and the experimental progresses that have been made for both rheumatoid arthritis and osteoarthritis, this review discusses the different gene therapy strategies available today and the safety issues with which they may be associated. Among the different vectors available today, adeno-associated virus seems the best candidate for a direct in vivo gene delivery approach for the treatment of joint disorders.
17642237 [CTLA4-Ig (abatacept)]. 2007 Jul Although tumor necrosis factor (TNF) antagonists have dramatically improved the outcome of patients with rheumatoid arthritis (RA), some of the patients do not respond or cannot tolerate these drugs. Abatacept is a recombinant fusion protein containing components of IgG and cytotoxic T-lymphocyte-associated antigen-4 that inhibit costimulatory signal from antigen presenting cells and prevent activation of T cells. Several clinical trials have demonstrated the excellent efficacy and safety of abatacept in patients with RA who are resistant to methotrexate or TNF antagonists. Abatacept improved clinical signs and symptoms and quality of life of patients with RA and also retarded their radiological progression of structural damage of affected joints. The safety concerns, especially for infections and malignancies, are raised and should be strictly monitored in clinical trials and future clinical practice in Japan as well as in Western countries.
17400667 Acute exacerbation of interstitial pneumonia other than idiopathic pulmonary fibrosis. 2007 Jul BACKGROUND: Acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) is increasingly recognized as a relatively common and highly morbid clinical event. However, clinical data on AE in non-IPF interstitial pneumonia are sparse. This study was performed to find the frequency, clinical features, and outcome of AE in non-IPF interstitial pneumonia. METHODS: Retrospective analysis of 10 patients who satisfied the modified Akira criteria for AE during follow-up of 74 patients with surgical lung biopsy-confirmed idiopathic nonspecific interstitial pneumonia (I-NSIP) and 93 patients with biopsy-confirmed interstitial pneumonia associated with collagen vascular disease (CVD-IP). RESULTS: AE occurred in six patients with I-NSIP (1-year frequency, 4.2%) and in four patients with CVD-IP (rheumatoid arthritis [RA], n = 3; scleroderma, n = 1), with 1-year frequency of 3.3%. Median age was 58 years (range, 47 to 75); six patients were female. AE occurred in two patients immediately after surgical biopsy. Median duration of acute symptom before hospital admission was 10 days (range, 1 to 30). Median ratio of Pao(2) to the fraction of inspired oxygen (Fio(2)) was 172 (range, 107 to 273), and Pao(2)/Fio(2) ratio was < 200 in six patients. Surgical lung biopsy performed at the time of AE in two patients revealed diffuse alveolar damage superimposed on nonspecific interstitial pneumonia pattern. Four patients with I-NSIP survived to discharge and were followed up for 24 months (range, 6 to 121). CONCLUSION: AE occurred in the patients with I-NSIP with apparently better prognosis. In patients with CVD-IP, AE occurred mostly with RA-usual interstitial pneumonia in our small series with poor outcome.
17902022 2-Deoxy-2-[F-18]fluoro-D-glucose joint uptake on positron emission tomography images: rheu 2007 Nov PURPOSE: Previous positron emission tomography (PET) studies have shown increased 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake in joints of patients with osteoarthritis (OA) and inflamed joints of patients with rheumatoid arthritis (RA). This study compares FDG uptake in joints of RA and OA patients and FDG-uptake with clinical signs of inflammation. PROCEDURES: FDG-PET scans of hands and wrists were performed in patients with RA and primary OA. PET data were compared with clinical data. RESULTS: 29% of RA joints and 6% of OA joints showed elevated FDG-uptake. The level of uptake in PET-positive OA joints was not significantly different from that in RA joints. The majority of PET results of RA joints corresponded with clinical findings. Clinical synovitis was found some OA joints with FDG-uptake. CONCLUSIONS: FDG-uptake was observed in the majority of clinically inflamed RA joints and in a few OA joints with no significant difference in uptake level. The latter may be due to secondary synovitis.
17493521 Not all "quality-adjusted life years" are equal. 2007 Jun BACKGROUND: There is evidence that utility elicitation methods used in the calculation of quality-adjusted life years (QALYs) yield different results. It is not clear how these differences impact economic evaluations. METHODS: Using a mathematical model incorporating data on efficacy, costs, and utility values, we simulated the experiences of 100,000 hypothetical rheumatoid arthritis patients over 10 years (50,000 exposed to infliximab plus methotrexate [MTX] and 50,000 exposed to MTX alone). QALYs, were derived from the Health Utilities Index 2 and 3 (HUI2 and HUI3), the Short Form 6-D (SF-6D), and the Euroqol 5-D (EQ-5D). Incremental cost-utility ratios were determined using each instrument to calculate QALYs and the results were compared using cost-effectiveness acceptability curves. RESULTS: Using the different utility measurement methods, the mean difference in QALYs between the infliximab plus MTX and MTX groups ranged from a high of 1.95 QALYs (95% CI=1.93-1.97) using the HUI3 to 0.89 QALYs (95% CI=0.88-0.91) using the SF-6D. Adopting the commonly cited value of society's willingness to pay for a QALY of $50,000, 91% of the simulations favored the cost utility of infliximab plus MTX when using the HUI3 to calculate QALYs. However, when using the EQ-5D, HUI2, or the SF-6D utility values to calculate QALYS, the proportion of simulations that favored the cost utility of infliximab were 63%, 45%, and 12%, respectively. CONCLUSION: Depending on the method for determining utility values used in the calculation of QALYs, very different incremental cost-utility ratios are generated.
16977346 NOD2 allele variants in patients with rheumatoid arthritis. 2007 Jun Recent reports have proven the importance of genetic factors and inflammation in the pathogenesis of rheumatoid arthritis (RA). In the current study, the frequency of NOD2/CARD15 gene variants (R702W, G908R, and L1007fsinsC) was examined in a group of 243 RA patients and 220 healthy controls. There were no statistically significant differences in distribution of NOD2 variant alleles between RA patients and controls. Moreover, there was no significant association between NOD2 variant alleles and joint erosions, extraarticular manifestations, rheumatoid factor, number of swollen and tender joints, and erythrocyte sedimentation rate. The results of the present study suggest that NOD2 allele variants have no significant influence on RA susceptibility, activity, and severity.
17642249 [Pneumonia, pneumocystis pneumonia]. 2007 Jul Pneumonia (almost equally bacterial) is the most common and serious adverse events of the patients with rheumatoid arthritis (RA) prescribing anti-tumor necrosis factor(TNF) agents. Furthermore, it has been shown that Pneumocystis jirovecii should be one of the important causal microorganisms by the results of postparketing all-patients registration surveillance in Japan. Older age, pulmonary comorbidities, diabetes mellitus, or dosage of co -prescribing glucocorticoid has been extracted as a predictable risk factor respectively and synergistically by the surveillance. When prescribing anti-TNF agents, it is possible that considering these risk factors might reduce the incidence of bacterial or Pneumocystis pneumonia in RA patients.
16362817 LST1 and NCR3 expression in autoimmune inflammation and in response to IFN-gamma, LPS and 2006 Jan Many genes in the central region of the major histocompatibility complex (MHC) encode proteins involved in immune and inflammatory responses. In this study, we have further characterized two genes in the MHC class IV region, leucocyte-specific transcript (LST) 1 and natural cytotoxicity-triggering receptor 3 (NCR3) (also known as 1C7 and natural killer (NK)p30). The specific function of LST1 is not known, although expression analysis and functional data suggest an immunomodulatory role. The LST1 gene undergoes extensive alternative splicing, giving rise to both membrane-bound (encoded by exon 3) and soluble isoforms. The NCR3 protein is involved in NK-mediated cytotoxicity and plays a role in NK/dendritic cell crosstalk. Expression of these genes was examined, by real-time reverse transcriptase-polymerase chain reaction, in autoimmune-induced inflammation, specifically rheumatoid-arthritis-affected blood and synovium, and in response to stimulation with inflammatory mediators and bacterial agents. The expression of LST1, specifically splice variants encoding soluble isoforms and NCR3, was increased in rheumatoid-arthritis-affected blood and synovium and was associated with more severe inflammation in the synovium. Furthermore, both genes were significantly up-regulated in response to lipopolysaccharide, interferon (IFN)-gamma and bacterial infection. These findings suggest that NCR3 and soluble isoforms of LST1 may play a role in inflammatory and infectious diseases.
16541480 Effects of infliximab treatment on lipoprotein profile in patients with rheumatoid arthrit 2006 May OBJECTIVE: To investigate the longterm effects of the anti-tumor necrosis factor (TNF) therapy infliximab, a drug known to reduce disease activity in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: Eighty-two patients (50 with RA, 32 with AS) aged 17-77 years were enrolled. All patients were treated with intravenous infliximab. Lipid profile was assessed at baseline and after 6 months of treatment. RESULTS: Disease activity significantly decreased in patients with RA and AS at the end of infliximab therapy. Infliximab treatment significantly increased total cholesterol from 206 to 216 mg/dl (p < 0.05) and triglycerides from 109 to 122 mg/dl (p < 0.05). The low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol did not change during treatment. Furthermore, the total cholesterol/HDL cholesterol and triglycerides/HDL cholesterol ratios did not change significantly. CONCLUSION: The influence of infliximab treatment on lipid profile seems to be neutral, since neither LDL cholesterol levels nor total cholesterol/HDL cholesterol and triglycerides/HDL cholesterol ratios changed significantly during the 6-month therapy. Our findings suggest that the favorable effect of infliximab treatment on cardiovascular comorbidity may not be mainly mediated by the effects on the lipid profile, but further investigations are needed in order to confirm this hypothesis.
18159199 [Surgical procedures for treatment of the rheumatoid knee]. 2007 Oct In the last decade considerable modifications in the surgical procedures recommended for the treatment of rheumatoid knee have been observed. This was due to all the medical developments achieved in pharmacology and therapeutic as well as a significant quality improvement of the rheumatologist s intervention. The synovectomy and namely the total knee arthroplasty represent the most commonly procedures used in the surgical treatment of the rheumatoid knee. An arthroscopic followed by a radionuclide synovectomy can be an appropriate treatment in a knee with an inflammatory arthritis Larsen radiograph grade I II . The ideal patient for synovectomy must present an early disease absence of deformity or instability good range of motion and preserved articular cartilage. On the other hand a total knee arthroplasty represents the only possible operation to treat a rheumatoid knee with a severe bone and cartilage damage Larsen radiograph grade IV V including younger patients. Total knee arthroplasty is actually a successful operation providing pain relief and the restoration of the function. Nevertheless the excellent good short and medium-term results achieved do not resist over time. Similarly to what happens with every other arthoplasty joint replacements the particules that come from the wear of the biomaterials included in its composition are the cause of biological intolerance reactions which can lead to the need of a new implant. The replacement prosthesis raises technical issues related to the reconstruction of bone mass losses where the cryopreserved bone allografts can be recommended.
19096851 Preliminary study on the immunologic background of good clinical outcome in rheumatoid art 2009 Jun This preliminary study focuses on early peripheral cellular immune changes after 1 month therapy with leflunomide, in 18 patients with severe rheumatoid arthritis, previously treated with methotrexate. A good clinical outcome of disease was documented and we showed that a particular target of short-time leflunomide therapy in rheumatoid arthritis was the peripheral innate immune system (NK cells and the population of granulocytes developing phagocytosis and superoxide anion production when challenged ex vivo with zymosan particles). Meanwhile, the high inter-individual variability of adaptive immunity required data analysis in subgroups of patients. We showed that the abnormal increase of peripheral leukocytes counts, or the decrease towards normal values of the CD4:CD8 lymphocytes ratio, or the inhibition of uridine uptake by ex vivo activated lymphocytes were consistent with a positive clinical evolution, proved by the reduction of tender/swollen joints, morning stiffness duration or acute phase response. We emphasized that significant benefits of short-term leflunomide therapy were associated with functional suppression of peripheral B lymphocytes. Hence, the positive evolution of rheumatoid arthritis patients seemed to be specifically linked to early drug-induced changes of trafficking or uridine metabolism of mononuclear cells.
18634161 Tumor necrosis factor-alpha -1031 T/C polymorphism is associated with smaller and more pro 2008 Sep OBJECTIVE: To study, in patients with rheumatoid arthritis (RA), the association between the tumor necrosis factor (TNF)-alpha -1031 T/C polymorphism and quantitative and qualitative low density lipoprotein (LDL) characteristics. METHODS: From a sample of 100 patients with RA and 100 controls, we used the strategy of "recruit by genotype" to select 30 patients with RA: 15 carriers of the rare allele (C) and 15 homozygous for the more frequent allele (T). These were matched with 30 controls. Plasma lipoprotein profile including size distribution of lipoproteins was determined using nuclear magnetic resonance spectrometry. LDL susceptibility to oxidation was assessed by diene formation. The LDL affinity for extracellular matrix was determined using electrophoretic mobility shift assay. Genotyping was performed by SnapShot. RESULTS: Compared to TT patients with RA, carriers of the C allele had (1) LDL particles significantly smaller [20.74 (0.68) nm vs 21.18 (0.52), p < 0.02]; (2) LDL particles with a greater affinity for the proteoglycans (i.e., with a lower Kd) [197.26 (123.98) nmol/l vs 259.26 (139.31), p = 0.05]; and (3) LDL particles with significantly greater susceptibility to oxidation [shorter lag phase: 47 (20.01) min vs 74 (41.8), p < 0.03, and higher maximal rate of diene production: 3.1 (0.5) mol/min vs 2.6 (0.95), p < 0.05]. None of these differences was observed in the control group. CONCLUSION: In patients with RA, genetic variability in the TNF-alpha gene is associated with smaller LDL particles that have a greater affinity for extracellular matrix and higher susceptibility to oxidation. Because these characteristics are associated with a greater risk of atherosclerosis, identification of such predisposition in patients with RA could help in implementing early preventive intervention measures against cardiovascular disease.
18448864 Modeling corticosteroid effects in a rat model of rheumatoid arthritis II: mechanistic pha 2008 Aug A mechanism-based model for pharmacodynamic effects of dexamethasone (DEX) was incorporated into our model for arthritis disease progression in the rat to aid in identification of the primary factors responsible for edema and bone loss. Collagen-induced arthritis was produced in male Lewis rats after injection of type II porcine collagen. DEX was given subcutaneously in single doses of 0.225 or 2.25 mg/kg or 7-day multiple doses of 0.045 or 0.225 mg/kg at 21 days postdisease induction. Effects on disease progression were measured by paw swelling, bone mineral density (BMD), body weights, plasma corticosterone (CST), and tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and glucocorticoid receptor (GR) mRNA expression in paw tissue. Lumbar and femur BMD was determined by PIXImus II dual-energy X-ray absorptiometry. Plasma CST was assayed by high-performance liquid chromatography. Cytokine and GR mRNA were assayed by quantitative real-time polymerase chain reaction. Indirect response models, drug interaction models, transduction processes, and the fifth-generation model of corticosteroid dynamics were integrated and applied using S-ADAPT software to describe how dexamethasone binding to GR can regulate diverse processes. Cytokine mRNA, GR mRNA, plasma CST, and paw edema were suppressed after DEX administration. TNF-alpha mRNA expression and BMD seemed to increase immediately after dosing but were ultimately reduced. Model parameters indicated that IL-6 and IL-1beta were most sensitive to inhibition by DEX. TNF-alpha seemed to primarily influence edema, whereas IL-6 contributed the most to bone loss. Lower doses of corticosteroids may be sufficient to suppress the cytokines most relevant to bone erosion.
17469099 Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a doubl 2007 May OBJECTIVE: To determine whether patients with undifferentiated arthritis (UA; inflammatory, nontraumatic arthritis that cannot be diagnosed using current classification criteria) benefit from treatment with methotrexate (MTX). METHODS: The PRObable rheumatoid arthritis: Methotrexate versus Placebo Treatment (PROMPT) study was a double-blind, placebo-controlled, randomized, multicenter trial involving 110 patients with UA who fulfilled the American College of Rheumatology (ACR) 1958 criteria for probable RA. Treatment started with MTX (15 mg/week) or placebo tablets, and every 3 months the dosage was increased if the Disease Activity Score was >2.4. After 12 months, the study medication was tapered and discontinued. Patients were followed up for 30 months. When a patient fulfilled the ACR criteria for RA (primary end point), the study medication was changed to MTX. Joint damage was scored on radiographs of the hands and feet. RESULTS: In 22 of the 55 patients (40%) in the MTX group, UA progressed to RA compared with 29 of 55 patients (53%) in the placebo group. However, in the MTX group, patients fulfilled the ACR criteria for RA at a later time point than in the placebo group (P = 0.04), and fewer patients showed radiographic progression over 18 months (P = 0.046). CONCLUSION: This study provides evidence for the efficacy of MTX treatment in postponing the diagnosis of RA, as defined by the ACR 1987 criteria, and retarding radiographic joint damage in UA patients.