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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
19632157 Depletion of B lymphocytes in rheumatoid arthritis patients modifies IL-8-anti-IL-8 autoan 2009 Oct Cytokines and chemokines are key regulatory molecules involved in rheumatoid arthritis (RA). B-cell depletion therapy improves RA clinically but its mechanism is not completely understood. One possible mechanism for this therapy is the modification of the proinflammatory cytokine homeostasis of RA. We show here that the levels of the proinflammatory chemokine IL-8 in serum samples from RA patients unexpectedly increased by up to 100-fold 8 weeks after the administration of rituximab, despite clinical improvement. We also show that RA patients produced anti-IL-8 autoantibodies and that their levels dropped after RTX treatment. Moreover, we identified antibody-IL-8 immune complexes in the synovial fluid and serum of RA patients, and found that the amount of these complexes decreased after the administration of RTX. Our results indicate that B-cell depletion therapy modifies the cytokine-autoantibody network by reducing the levels of anti-cytokine autoantibodies and, consequentially, the formation of antibody-cytokine immune complexes.
20516025 Lipoprotein subclasses determined by nuclear magnetic resonance spectroscopy and coronary 2010 Aug 1 OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of atherosclerosis, but routine lipid measurements differ little from those of people without RA. We examined the hypothesis that lipid subclasses determined by nuclear magnetic resonance spectroscopy (NMR) differed in patients with RA compared to controls and are associated with disease activity and the presence of coronary-artery atherosclerosis. METHODS: We measured lipoprotein subclasses by NMR in 139 patients with RA and 75 control subjects. Lipoproteins were classified as large low-density lipoprotein (LDL; diameter range 21.2-27.0 nm), small LDL (18.0-21.2 nm), large high-density lipoprotein (HDL; 8.2-13.0 nm), small HDL (7.3-8.2 nm), and total very low-density lipoprotein (VLDL; >or= 27 nm). All subjects underwent an interview and examination; disease activity was quantified by the 28-joint Disease Activity Score (DAS28) and coronary artery calcification (CAC) was measured with electron-beam computed tomography. RESULTS: Concentrations of small HDL particles were lower in patients with RA (18.2 +/- 5.4 nmol/l) than controls (20.0 +/- 4.4 nmol/l; p = 0.003). In patients with RA, small HDL concentrations were inversely associated with DAS28 (rho = -0.18, p = 0.04) and C-reactive protein (rho = -0.25, p = 0.004). Concentrations of small HDL were lower in patients with coronary calcification (17.4 +/- 4.8 nmol/l) than in those without (19.0 +/- 5.8 nmol/l; p = 0.03). This relationship remained significant after adjustment for the Framingham risk score and DAS28 (p = 0.025). Concentrations of small LDL particles were lower in patients with RA (1390 +/- 722 nmol/l) than in controls (1518 +/- 654 nmol/l; p = 0.05), but did not correlate with DAS28 or CAC. CONCLUSION: Low concentrations of small HDL particles may contribute to increased coronary atherosclerosis in patients with RA.
20852893 Rare variation at the TNFAIP3 locus and susceptibility to rheumatoid arthritis. 2010 Dec Genome-wide association studies (GWAS) conducted using commercial single nucleotide polymorphisms (SNP) arrays have proven to be a powerful tool for the detection of common disease susceptibility variants. However, their utility for the detection of lower frequency variants is yet to be practically investigated. Here we describe the application of a rare variant collapsing method to a large genome-wide SNP dataset, the Wellcome Trust Case Control Consortium rheumatoid arthritis (RA) GWAS. We partitioned the data into gene-centric bins and collapsed genotypes of low frequency variants (defined here as MAF ≤ 0.05) into a single count coupled with univariate analysis. We then prioritized gene regions for further investigation in an independent cohort of 3,355 cases and 2,427 controls based on rare variant signal p value and prior evidence to support involvement in RA. A total of 14,536 gene bins were investigated in the primary analysis and signals mapping to the TNFAIP3 and chr17q24 loci were selected for further investigation. We detected replicating association to low frequency variants in the TNFAIP3 gene (combined p = 6.6 × 10(-6)). Even though rare variants are not well-represented and can be difficult to genotype in GWAS, our study supports the application of low frequency variant collapsing methods to genome-wide SNP datasets as a means of exploiting data that are routinely ignored.
19238330 Chronic increases in sphingosine kinase-1 activity induce a pro-inflammatory, pro-angiogen 2009 Sphingosine kinase-1 (SK1) promotes the formation of sphingosine-1-phosphate (S1P), which has potent pro-inflammatory and pro-angiogenic effects. We investigated the effects of raised SK1 levels on endothelial cell function and the possibility that this signaling pathway is activated in rheumatoid arthritis. Human umbilical vein endothelial cells with 3- to 5-fold SK1 (EC(SK)) overexpression were generated by adenoviral and retroviralmediated gene delivery. The activation state of these cells and their ability to undergo angiogenesis was determined. S1P was measured in synovial fluid from patients with RA and OA. EC(SK) showed an enhanced migratory capacity and a stimulated rate of capillary tube formation. The cells showed constitutive activation as evidenced by the induction of basal VCAM-1 expression, and further showed a more augmented VCAM-1 and E selectin response to TNF compared with empty vector control cells (EC(EV)). These changes had functional consequences in terms of enhanced neutrophil binding in the basal and TNFstimulated states in EC(SK). By contrast, over-expression of a dominant-negative SK inhibited the TNF-induced VCAM-1 and E selectin and inhibited PMN adhesion, confirming that the observed effects were specifically mediated by SK. The synovial fluid levels of S1P were significantly higher in patients with RA than in those with OA. Small chronic increases in SK1 activity in the endothelial cells enhance the ability of the cells to support inflammation and undergo angiogenesis, and sensitize the cells to inflammatory cytokines. The SK1 signaling pathway is activated in RA, suggesting that manipulation of SK1 activity in diseases of aberrant inflammation and angiogenesis may be beneficial.
19626390 Prospective study of methotrexate treatment for rheumatoid arthritis treated legitimately 2009 Clinical squeal of the treatment of rheumatoid arthritis patients with methotrexate (MTX) according to the Japanese government recommended dose of 8 mg/week was evaluated prospectively. A total of 176 patients with active RA attending Konan Kakogawa Hospital and Kobe University Hospital were enrolled. Patients' profile at the start of study was Class 2.0 +/- 1.1 and X-ray stage 2.6 +/- 1.0. The effects of MTX treatment were evaluated by the American College of Rheumatology (ACR) core set, disease activity score of 28 joints (DAS28), and European League Against Rheumatism (EULAR) response criteria. A modified Sharp method was used to evaluate the radiographs. The improvement in the clinical signs and symptoms of the ACR core set was maintained for a 24-month period (p < 0.05). The ACR20/50/70 and DAS28 were also improved at the 12- and 24-month assessments. However, 82 of 130 patients (63.5%) were found to be nonresponders at 24 months of MTX therapy, as evaluated by EULAR response criteria. The X-ray study showed that joint destruction progressed despite the treatment. Thus, long-term MTX treatment performed in accordance with the Japanese 8 mg/week regimen appears to be favorable in terms of the signs and symptoms of RA; however, it is clearly insufficient for and cannot halt the progression of rheumatic joint destruction.
19180477 Genetic risk factors for rheumatoid arthritis differ in Caucasian and Korean populations. 2009 Feb OBJECTIVE: Recent studies have identified a number of novel rheumatoid arthritis (RA) susceptibility loci in Caucasian populations. The aim of this study was to determine whether the genetic variants at 4q27, 6q23, CCL21, TRAF1/C5, and CD40 identified in Caucasians are also associated with RA in a Korean case-control collection. We also comprehensively evaluated the genetic variation within PTPN22, a well-established autoimmune disease-associated gene. METHODS: We designed an experiment to thoroughly evaluate the PTPN22 linkage disequilibrium region, using tag single-nucleotide polymorphisms (SNPs) and disease-associated SNPs at 5 RA-associated loci recently identified in Caucasians, in 1,128 Korean patients with RA and 1,022 ethnically matched control subjects. We also resequenced the PTPN22 gene to seek novel coding variants that might be contributing to disease in this population. RESULTS: None of the susceptibility loci identified in Caucasian patients with RA contributed significantly to disease in Koreans. Although tag SNPs covering the PTPN22 linkage disequilibrium block were polymorphic, they did not reveal any disease association, and resequencing did not identify any new common coding region variants in this population. The 6q23 and 4q27 SNPs assayed were nonpolymorphic in this population, and the TRAF1/C5, CD40, and CCL21 SNPs did not show any evidence for association with RA in this population of Korean patients. CONCLUSION: The genetic risk factors for RA are different in Caucasian and Korean patients. Although patients of different ethnic groups share the HLA region as a major genetic risk locus, most other genes shown to be significantly associated with disease in Caucasians appear not to play a role in Korean patients with RA.
19373885 Myasthenia gravis associated with etanercept therapy. 2009 Jun Etanercept is an antagonist of tumor necrosis factor alpha that was developed to treat rheumatoid arthritis. In this report we present a patient who developed myasthenia gravis while taking etanercept and had resolution of symptoms after stopping it. This is the first report of this potential side effect and is of additional interest, because etanercept has been proposed as a treatment for myasthenia gravis.
19597733 Adiponectin and leptin serum concentrations in patients with rheumatoid arthritis. 2010 Apr Adipose tissue is regarded as an active metabolic and endocrine organ producing adipokines. The purpose of the study was to evaluate adiponectin and leptin concentrations in rheumatoid arthritis (RA) patients (pts) in relation to disease duration and activity. The study group consisted of 80 RA pts. Serum adiponectin and leptin concentrations remained within normal ranges. Adiponectin concentration correlated positively both with the age and disease duration. Both adipokines levels correlated negatively with glomerular filtration rate. There were significant positive correlations between adipokines' concentrations and lipid profile components (between adiponectin and HDL-cholesterol, leptin and total cholesterol and LDL-cholesterol). In pts with long-standing RA, there was a negative correlation between adiponectin and numbers of tender, swollen joints and a positive relationship between leptin level and DAS28. The results confirm adipokines' involvement in the process of inflammation and atherosclerosis: protective and antiinflammatory adiponectin effect and proatherogenic and proinflammatory leptin function.
20732648 Treating to re-establish tolerance in inflammatory arthritis - lessons from other diseases 2010 Aug Therapeutic tolerance embraces the concept of 'switching off' immunopathology by specifically targeting elements of the immune system. It has been achievable in preclinical models of transplantation and auto-immunity for more than two decades; however, previous attempts to translate to the clinic have been unsuccessful. Nonetheless, an improved understanding of tolerance mechanisms, along with novel therapeutic agents and strategies, are starting to bear fruit in a number of disease areas. True tolerance is achievable in transplantation settings, and long-term remissions can be induced in various auto-immune and atopic conditions. Equivalent outcomes should be achievable in inflammatory arthritis, although this may require an improved understanding of the immune dysregulation that is intrinsic to rheumatoid arthritis (RA), and better definitions of RA autoantigens. Biomarkers of tolerance induction would rapidly advance the field in all therapeutic areas. This article summarises the advances made in other therapeutic areas, and the lessons learned that we can now apply to RA.
21062853 The extent of the anti-citrullinated protein antibody repertoire is associated with arthri 2011 Jan OBJECTIVES: To determine the fine specificity of anti-citrullinated protein antibodies (ACPA) in the early phase of arthritis development, the ACPA repertoire in arthralgia patients and the association with arthritis development were studied. METHODS: A total of 244 patients with arthralgia positive for anti-cyclic citrullinated peptide antibodies (aCCPs) and/or IgM rheumatoid factor (IgM-RF), without arthritis were included. Development of arthritis was defined as presence of one or more swollen joints at clinical examination during follow-up. Sera were tested at baseline for reactivity to five citrullinated peptides derived from fibrinogen (three), vimentin (one) and α-enolase (one) and five corresponding arginine peptides in an ELISA. RESULTS: In all, 69 patients (28%) developed arthritis in a median of 3 joints after a median follow-up of 11 (IQR 5-20) months. Reactivity to each peptide was significantly associated with arthritis development (p<0.001). The ACPA repertoire did not differ between patients who did or did not develop arthritis. Among aCCP-positive patients, patients recognising two or more additional citrullinated peptides developed arthritis more often (p=0.04). The number of recognised peptides was positively associated with the aCCP level (p<0.001). Crossreactivity between different peptides was minimal. CONCLUSIONS: Arthritis development is not associated with recognition of a specific citrullinated peptide once joint complaints are present. The ACPA repertoire in some patients with arthralgia is expanded. High aCCP levels are associated with a qualitatively broad ACPA repertoire. Patients with an extended ACPA repertoire have a higher risk of developing arthritis.
20473501 Antibodies against cyclic citrullinated peptide don't decrease after 6 months of inflixima 2011 Nov Anti-citrullinated peptide antibodies (ACPA) and the rheumatoid factor (RF) are well-established serological markers for rheumatoid arthritis (RA). ACPA are very useful in the diagnosis of RA, especially at the early stages of the disease when ACPA have a greater diagnostic value than RF. The aim of the study was to assess the influence of infliximab treatment on RF IgM and ACPA serum levels and RA activity during 6 months of treatment. Thirty-two patients with refractory RA were treated with infliximab during a 6-month period. At baseline, 3 and 6 months of treatment the patients were examined for the number swollen and tender joints out of 28 (SJC, TJC) and the visual analogue scale of arthritis activity according to the patient (VAS). Serum samples were tested for erythrocyte sedimentation rate (ESR), C-reactive protein level (CRP), ACPA and RF IgM. The disease activity score (DAS-28) parameter was also calculated at the same time. During the course of our study, we observed statistically significant improvement in ESR, CRP, TJC, SJC, VAS DAS-28, and RF IgM after 3 and 6 months of infliximab treatment when compared to the baseline, whereas the ACPA level remained unchanged after 3 and 6 months of treatment (P = 0.96 and P = 0.85). The changes in the ACPA level are not a factor for evaluation of successful infliximab treatment but the changes in RF IgM are. According to different behavior of these antibodies during infliximab treatment, we suggest that the roles of ACPA and RF in the pathogenesis of RA are different.
21044436 Long-term safety of methotrexate in the treatment of rheumatoid arthritis. 2010 Sep Methotrexate (MTX) has been the anchor treatment in rheumatoid arthritis (RA) over the last 15 years, and is used in combination with biologic agents to enhance efficacy over the last decade or so. The safety profile of MTX has been studied over 25 years with very few clinically important adverse events in the weekly low-doses used for RA treatment. The importance of MTX in earlier and more aggressive management of RA patients cannot be overstated. MTX courses show some of the longest continuation rates reported in clinical medicine, due to both effectiveness and safety. The safety profile of MTX indicates that it is among the safest of any mediation used for the treatment of any arthritis. Better information on the effectiveness and safety of weekly-low dose MTX should be communicated to all health professionals involved in the management of RA patients.
19283524 Plasma total homocysteine level and methylenetetrahydrofolate reductase 677C>T genetic pol 2009 Feb Hyperhomocysteinemia is a known risk factor of cardiovascular disease. Homocysteine has been also linked to inflammation in rheumatoid arthritis (RA). In this study, we investigated the relationship between plasma homocysteine levels and single nucleotide polymorphism (SNP) of the gene coding for methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in the biosynthesis of homocysteine, and the correlation between the plasma homocysteine levels and generally used inflammatory markers (C-reactive protein, erythrocyte sedimentation rate and matrix metalloproteinase-3) in 96 Japanese patients with RA. Plasma homocysteine levels in patients with the MTHFR 677TT genotype were significantly higher than in those with the 677CC genotype (p < 0.05). In addition, plasma homocysteine levels were increased along with the elevation of general inflammatory markers. Therefore, we conclude that homocysteine might affect the inflammatory status of patients, and the MTHFR 677C>T SNP could be a predictive factor of hyperhomocysteinemia in patients with RA.
19663190 [Combined basic therapy of rheumatoid arthritis with methotrexate and plaquenil]. 2009 AIM: To compare efficacy of basic RA treatment with methotrexate+plaquenil and basic monotherapy with methotrexate. MATERIAL AND METHODS: Two groups of rheumatoid arthritis (RA) patients were studied: group 1 (n = 82) received combined basic treatment with methotrexate (7.5 mg/week) in combination with plaquenil (0.2 ?mg/day); group 2 (n = 60) received methotrexate monotherapy according to the same scheme; all the patients received also diclofenak in a dose 100 mg/day; low-dose glucocorticosteroids were given to 36 and 24 patients, respectively. To improve methotrexate tolerance, all the patients took folic acid (1-2 mg/day 5 days a week). Efficacy of the treatment was evaluated by regression and final value of inflammation activity. RESULTS: 6-month treatment produced in groups 1 and 2 good effect in 27.6 and 21.4%, satisfactory effect--in 65.5 and 66.6% patients, respectively. No effect was seen in 6.8 and 11.9% patients, respectively. A good effect was achieved in group 1 in 73.3 +/- 5.4 days; in group 2--in 93.7 +/- 5.9 days (p < 0.05). In 12 months good and satisfactory effects persisted. Side effects occurred with the same frequency in both groups primarily in those who did not take folic acid. CONCLUSION: Combined basic therapy of RA with methotrexate and plaquenil was more effective than monotherapy with methotrexate because it produced good effects more frequently and earlier while no response was seen less often.
19539849 Methotrexate-related lymphoproliferative disorder with extensive vascular involvement in a 2009 Jul We describe the development of a cutaneous lymphoproliferative disorder in a patient with rheumatoid arthritis who was treated with methotrexate. Skin manifestations were characterized by thrombophlebitis-like lesions and ulcerated nodules. Histologic examination revealed large polymorphic atypical cells including Reed-Sternberg-like cells expressing CD20 and CD30 in the dermis and subcutaneous tissues. Tumor cells infiltrated the walls of dermal arterioles, subcutaneous arteries, and veins, leading to the destruction of vascular structures. Activation of Epstein-Barr virus was detected. Skin lesions improved remarkably after the discontinuation of methotrexate. This case illustrates the rare occurrence of cutaneous vascular involvement in methotrexate-related lymphoproliferative disorder that did not require any specific chemotherapy.
20813405 Ionic complex systems based on hyaluronic acid and PEGylated TNF-related apoptosis-inducin 2010 Dec The clinical applications of tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL), an emerging therapeutic protein for cancer and rheumatoid arthritis (RA), are limited by its instability and short biological half-life. In this study, efficient therapeutic modalities for RA treatment were developed in the form of nano-sized complexes (nanocomplexes) based on hyaluronic acid (HA) and polyethylene glycol (PEG)-derivatized TRAIL (PEG-TRAIL) formed by N-terminal specific PEGylation. The nanocomplexes were prepared by simply mixing the positively charged PEG-TRAIL and negatively charged HA, and showed negligible loss of bioactivity compared with the PEG-TRAIL. The in vivo biodistribution and diffusion kinetics of Cy5.5-labeled PEG-TRAIL in mice were observed using a near-infrared optical imaging system after subcutaneous injection of three different formulations: PEG-TRAIL in phosphate-buffered saline (PBS, pH 7.4), nanocomplex in PBS, or nanocomplex in 1% HA solution. The results suggested that PEG-TRAIL is released slowly in vivo from the nanocomplex in 1% HA. Experiments in a collagen-induced arthritis mouse model demonstrated that the magnitudes of therapeutic effects, as judged by clinical scores and histology, were significantly enhanced by the sustained delivery of PEG-TRAIL, with the order of nanocomplex in 1% HA>nanocomplex in PBS>PEG-TRAIL in PBS. In addition, sustained delivery of PEG-TRAIL from the nanocomplex in 1% HA resulted in significant reduction of serum inflammatory cytokines and collagen-specific antibodies that are responsible for the pathogenesis of RA. These results imply that HA/PEG-TRAIL nanocomplex formulations are promising therapeutic modalities for the treatment of RA.
20190509 [Onset of modified measles after etanercept treatment in rheumatoid arthritis]. 2010 Treatment with corticosteroid and etanercept was started for a 69-year-old woman with rheumatoid arthritis. Eight weeks later, she developed fever and anorexia, and was admitted to our hospital with a poor general condition. With the suspicion of bacterial infection, antibiotic treatment was started on the first hospital day, but was ineffective. From the fourth hospital day, multiple generalized, partially confluent, erythematous papules appeared. To exclude viral infection, we measured antibody titers against various viruses, and found that the levels of anti-measles IgG and IgM antibodies were elevated, which led to a diagnosis of modified measles. During the course of measles, she developed severe leukopenia, and bone marrow aspiration revealed bone marrow suppression. This was considered to be due to measles infection, leading to a diagnosis of severe modified measles. This is the first case report of modified measles which developed during the use of an anti-TNF-alpha preparation, and suggests that immunosuppression induced by the preparation may play a role in measles reinfection and its aggravation.
20517583 mTOR regulates the invasive properties of synovial fibroblasts in rheumatoid arthritis. 2010 Sep The invasive properties of fibroblast-like synoviocytes (FLS) correlate with radiographic and histologic damage in rheumatoid arthritis (RA) and pristane-induced arthritis (PIA). We previously determined that highly invasive FLS obtained from PIA-susceptible DA (blood type D, Agouti) rats have increased expression of genes associated with invasive cancers, including Villin-2/ezrin. Villin-2/ezrin mediates invasion via mTOR. In the present study we used the mTOR inhibitor rapamycin to assess the role of the ezrin-mTOR pathway on the invasive properties of FLS. FLS were isolated from synovial tissues from arthritic DA rats, and from RA patients. FLS were treated with rapamycin or dimethyl sulfoxide (DMSO) for 24 h and then studied in a Matrigel-invasion assay. Supernatants were assayed for matrix metalloproteinase (MMP) activity, and cell lysates were used for quantification of mTOR, p70S6K1, 4EBP1 and FAK, as well as their respective phosphorylated subsets. Actin filament and FAK localization were determined by immunofluorescence. Rapamycin decreased FLS invasion in DA and RA tissues by 93% and 82%, respectively. Rapamycin treatment reduced the phosphorylation of mTOR and its substrates, p70S6K1 and 4EBP1, confirming mTOR inhibition. In conclusion, rapamycin prevented actin reorganization in both DA and RA FLS, and inhibited the directional formation of lamellipodia. Phosphorylation of the lamellipodia marker FAK was also reduced by rapamycin. MMPs were not significantly affected by rapamycin. Rapamycin significantly reduced RA and DA rat FLS invasion via the suppression of the mTOR signaling pathway. This discovery suggests that rapamycin could have a role in RA therapy aimed at reducing the articular damage and erosive changes mediated by FLS.
19015207 Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis 2009 Jun BACKGROUND: Certolizumab pegol is a PEGylated tumour necrosis factor inhibitor. OBJECTIVE: To evaluate the efficacy and safety of certolizumab pegol versus placebo, plus methotrexate (MTX), in patients with active rheumatoid arthritis (RA). METHODS: An international, multicentre, phase 3, randomised, double-blind, placebo-controlled study in active adult-onset RA. Patients (n = 619) were randomised 2:2:1 to subcutaneous certolizumab pegol (liquid formulation) 400 mg at weeks 0, 2 and 4 followed by 200 mg or 400 mg plus MTX, or placebo plus MTX, every 2 weeks for 24 weeks. The primary end point was ACR20 response at week 24. Secondary end points included ACR50 and ACR70 responses, change from baseline in modified Total Sharp Score, ACR core set variables and physical function. RESULTS: Significantly more patients in the certolizumab pegol 200 mg and 400 mg groups achieved an ACR20 response versus placebo (p< or =0.001); rates were 57.3%, 57.6% and 8.7%, respectively. Certolizumab pegol 200 and 400 mg also significantly inhibited radiographic progression; mean changes from baseline in mTSS at week 24 were 0.2 and -0.4, respectively, versus 1.2 for placebo (rank analysis p< or =0.01). Certolizumab pegol-treated patients reported rapid and significant improvements in physical function versus placebo; mean changes from baseline in HAQ-DI at week 24 were -0.50 and -0.50, respectively, versus -0.14 for placebo (p< or =0.001). Most adverse events were mild or moderate, with low incidence of withdrawals due to adverse events. Five patients developed tuberculosis. CONCLUSION: Certolizumab pegol plus MTX was more efficacious than placebo plus MTX, rapidly and significantly improving signs and symptoms of RA and physical function and inhibiting radiographic progression. TRIAL REGISTRATION NUMBER: NCT00175877.
20008093 First-line DMARD choice in early rheumatoid arthritis--do prognostic factors play a role? 2010 Jul OBJECTIVE: To examine if prognostic factors predict the choice of first DMARD for patients with RA. METHODS: Details of 616 patients with early RA were collected from 16 centres in the UK Early Rheumatoid Arthritis Network (ERAN). Logistic regression was used to identify whether HAQ score, swollen joint count (SJC), nodules, RF, ESR, CRP and erosions on radiographs were associated with the choice of first DMARD treatment. RESULTS: Of 616 patients, 547 (88%) were started on a DMARD, 253 (46%) on MTX, 230 (42%) on SSZ, 47 (9%) on other DMARD monotherapies and 17 (3%) on combination DMARD therapy (CoT). SSZ was started less frequently in patients with positive RF (P = 0.018; OR 0.59; 95% CI 0.38, 0.91) and high SJC (P = 0.02; OR 0.95; 95% CI 0.91, 0.99). MTX was favoured in patients with high SJC (P = 0.002; OR 1.07; 95% CI 1.02, 1.11). Non-prescription of DMARDs was associated with old age (P = 0.02; OR 0.98; 95% CI 0.96, 0.99) and low HAQ score (P = 0.009; OR 0.80; 95% CI 0.68, 0.95). None of the variables predicted CoT. All other variables and the hospital where the patient was treated were not independently associated with the choice of DMARD. CONCLUSIONS: When choosing DMARD monotherapy in early RA, rheumatologists in ERAN seem to preferentially prescribe MTX for patients with a poor prognosis and SSZ for patients with good prognosis. No DMARDs were used in older patients or in those with a low HAQ.