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ID PMID Title PublicationDate abstract
23545592 Role of methotrexate polyglutamation and reduced folate carrier 1 (RFC1) gene polymorphism 2013 The aims of the present study were to define inter-individual differences in response to methotrexate (MTX) through MTX polyglutamate (MTX-PG) levels in red blood cells (RBC) and MTX-related gene polymorphisms. A total of 145 rheumatoid arthritis patients were recruited. MTX-PG1-5 concentrations in RBC were measured, and 11 single nucleotide polymorphisms, all in MTX-related genes involved in the folate pathway, were analyzed. Disease activity was also assessed. There was no direct relationship between any MTX-PG concentration and the patient's disease condition, but detectability of MTX-PG5 was extracted as a candidate marker for response to MTX. When disease activity was compared between patients in which MTX-PG5 was detectable and undetectable, all indexes except the visual analog scale (VAS) and C-reactive protein (CRP) were found to be significantly lower in the former patients. Reduced folate carrier 1 (RFC1) 80G>A was significantly associated with the detectability of MTX-PG5; detectability of MTX-PG5 was lower in patients with the A mutant allele. The present study suggests that detectability of MTX-PG5 in RBC is a possible biomarker for response to MTX, and the RFC1 80G>A mutation is associated with low detectability of MTX-PG5. Prospective studies with a sufficient number of patients are needed to confirm the present findings.
24870843 [Biologic agents for the treatment of rheumatic diseases]. 2014 Jun Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by chronic synovitis and bone damage. Bone homeostasis is maintained by a balance between bone resorption and bone formation. It is also involved by immune systems and imbalance in immune system often results in pathological processes such as joint destruction as well as secondary osteoporosis. Proinflammatory cytokines such as TNF and IL-6 cause an imbalance in bone metabolism via direct and/or indirect effects on osteoclasts. However, the combination of methotrexate and biologic DMARDs targeting TNF and IL-6 have revolutionized the treatment of RA, producing significant improvements in clinical, radiographic, and functional outcomes that were not previously observed. Such progress in the treatment of RA has been expanded to other joint diseases including psoriatic arthritis, spodylarthritis and so on.
22689315 Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on ri 2013 Mar BACKGROUND: Studies examining the relationship between serological status (rheumatoid factor and/or anticitrullinated antibody) and rituximab treatment outcome in rheumatoid arthritis (RA) have been hampered by limited numbers of seronegative patients. OBJECTIVE: To carry out a meta-analysis of trials from the rituximab RA clinical programme to investigate this relationship further. METHODS: This was a meta-analysis of four placebo-controlled, phase II or III clinical trials. The efficacy end point in all analyses was change from baseline in Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 24 weeks. Assay of serotype and missing data imputation methods were consistent across all studies. RESULTS: The population analysed comprised 2177 patients (rituximab, n=1416; placebo, n=761). Demographics and baseline disease characteristics were well balanced. When a fixed-effects meta-analysis approach was used, the overall-effect model indicated evidence of additional treatment benefit with rituximab in seropositive patients: reduction in DAS28-ESR at week 24 was on average 0.35 units (95% CI 0.12 to 0.84; n=1394) greater than in seronegative patients; this effect was not seen in placebo patients. Heterogeneity indices indicated significant uncertainty in the overall-effect model (Q=8.8, I=0.77; p=0.03 (χ(2) test)). Baseline Health Assessment Questionnaire score, pain visual analogue scale, swollen joint counts of 28 joints and race were significant contributors to this heterogeneity, with additional analysis indicating that these effects may predominate in early RA (methotrexate-naïve) populations. A dominant effect was seen in patients for whom one or more tumour necrosis factor inhibitors had failed. CONCLUSION: Although the difference was modest, the overall-effect model indicates that seropositive patients respond better to rituximab than seronegative patients.
22679306 Decline in work disability caused by early rheumatoid arthritis: results from a nationwide 2013 May OBJECTIVES: To study whether the work disability (WD) rates in early rheumatoid arthritis (RA) have changed in Finland, where the treatment of RA has long been active but has intensified further since 2000. METHODS: All incident non-retired patients with RA of working age (18-64 years) in a nationwide register maintained by the Finnish Social Insurance Institution from 1 January 2000 to 31 December 2007 were identified. Patient cohorts were analysed in 2-year time periods (2000-1, 2002-3, 2004-5, 2006-7) and initial disease-modifying antirheumatic drugs (DMARDs) were elucidated from the drug purchase register. The incidence of continuous WD in the RA cohorts as well as in the entire Finnish population up to 31 December 2008 was analysed. RESULTS: A total of 7831 patients were identified (71% women, 61% rheumatoid factor-positive). Throughout the follow-up period the use of methotrexate and combination DMARDs as the initial treatment of early RA increased. During the first 2 years the incidence of RA-related continuous WD was 8.9%, 9.4%, 7.2% and 4.8% in the year cohorts, respectively (p<0.001 for linearity). Compared with the entire Finnish population, the age- and sex-stratified standardised incidence ratio of a WD pension due to any cause was 3.69, 3.34, 2.77 and 2.80 in the year cohorts, respectively (p<0.001 for linearity). CONCLUSIONS: Since 2000 the frequency of continuous WD in early RA has declined in Finland. The present data allow no explanatory analysis but, at the same time, increasingly active treatment strategies have been introduced.
24252054 Confirmation of effectiveness of tocilizumab by ultrasonography and magnetic resonance ima 2015 Efficacy of tocilizumab in active early-stage RA patients despite methotrexate was evaluated for 12 months. One out of 5 patients was quitted by infusion reaction whereas tocilizumab continued for 12 months in the remaining 4 patients. Power Doppler articular synovitis was reduced in every patient and disappeared in 2 patients. Marked MRI osteitis, found in 1 patient, had disappeared at 12 months. Present results confirm the efficacy of tocilizumab by ultrasonography and MRI.
24535543 Genetic and epigenetic predictors of responsiveness to treatment in RA. 2014 Jun Methotrexate and TNF-blocking agents are the DMARDs most commonly prescribed for the treatment of rheumatoid arthritis (RA). However, not all patients treated with these nonbiologic and biologic DMARDs respond satisfactorily and few predictors of treatment efficacy have been identified, despite the fact that these therapies have now been available for many years. Many studies have investigated genetic factors that might predict patient responsiveness to therapies used to treat RA, and epigenetic studies regarding response to treatment are expected to accumulate in the literature in the near future. Herein, we review the advances in identifying genetic and epigenetic predictors of therapeutic responses to methotrexate and/or TNF inhibitors in RA that have been made to date, and highlight important considerations for future studies, such as the need for an improved, preferably biological, outcome measure reflecting response to treatment.
23457387 Evaluation of serum biomarkers associated with radiographic progression in methotrexate-na 2013 May OBJECTIVE: To evaluate associations between biomarkers and radiographic progression in methotrexate (MTX)-naive patients with rheumatoid arthritis (RA) treated with MTX or golimumab, a tumor necrosis factor inhibitor (with or without MTX). METHODS: Serum samples from 152 MTX-naive adults with active RA who received placebo + MTX (n = 37) or golimumab (combined 50 mg + MTX or 100 mg ± MTX; n = 115) were analyzed for selected markers of inflammation and bone/cartilage turnover. One hundred patients were randomly selected for additional protein profiling using multianalyte profiles (HumanMap v1.6, Rules Based Medicine). Radiographs at baseline, Week 28, and Week 52 were scored using van der Heijde-Sharp (vdH-S) methodology. Correlations were assessed between biomarker levels (baseline and change at Week 4) and joint space narrowing, erosion, and total vdH-S scores (changes at Weeks 28 and 52). Statistical significance was defined as a correlation coefficient with an absolute value ≥ 0.3 and p < 0.05. RESULTS: Biomarker correlations with changes in vdH-S scores at Week 28 and/or 52 were observed predominantly in the placebo + MTX group and rarely in the combined golimumab treatment group. Changes in epidermal growth factor (EGF) and CD40 ligand (CD40L) at Week 4 were positively correlated with changes in total vdH-S scores at Weeks 28 and 52 in the placebo + MTX group. CONCLUSION: These preliminary findings indicate that EGF and CD40L may have utility in monitoring MTX-treated patients with RA who are more likely to have radiographic progression as measured by increases in vdH-S scores.
23719982 [A case of myasthenia gravis following sarcoidosis and rheumatoid arthritis]. 2013 We report an elderly woman with sarcoidosis and rheumatoid arthritis who subsequently developed myasthenia gravis. She was given a diagnose of rheumatoid arthritis at the age of 65 years and sarcoidosis, proved by multiple lymphadenopathy with noncaseating granuloma at the age of 67. Prednisolone, methotrexate, and etanercept had been administrated for rheumatoid arthritis. She consulted our hospital because of bilateral ptosis with diurnal fluctuation at the age of 72. Myasthenia gravis was confirmed by an elevated serum anti-acetylcholine receptor antibody titer (1,100 nmol/l, normal <0.2) and a positive edrophonium test. A chest CT showed a small granular structure in the anterior mediastinum, suggesting thymic hyperplasia. This is the first reported case of myasthenia gravis complicated by sarcoidosis and rheumatoid arthritis. Administration of etanercept may be involved in the onset of myasthenia gravis.
23634781 Baseline factors predicting change from the initial DMARD treatment during the first 2 yea 2013 May 1 BACKGROUND: Outcomes in early Rheumatoid Arthritis (RA) may be improved by rapidly establishing a stable and effective disease modifying anti-rheumatic drug (DMARD) treatment regimen. We aimed to investigate whether baseline factors and initial treatment strategies are associated with changes to the first DMARD treatment, due to either Lack of Efficacy (LoE) or Adverse Drug Reaction (ADR) within 2 years of presentation. METHODS: Reasons for changes from initial DMARD therapy within 2 years of baseline, and associated factors, were examined using logistic regression in data from the Early RA Network (ERAN) inception cohort. RESULTS: Data were available for 766 participants. 410 (54%) changed their initial DMARD regime within 2 years, including 230 (56%) due to Lack of Efficacy (LoE) and 139 (34%) due to Adverse Drug Reaction (ADR). The first DMARD was recorded as methotrexate monotherapy in 336 (44%), sulphasalazine monotherapy in 273 (36%), or combined methotrexate/sulphasalazine/hydroxychlorquine in 52 (7%).Baseline predictors of changing DMARD (for all reasons) were HAQ-disability (aOR 1.44, 95% CI 1.12 - 1.86), poor mental health (aOR 1.44, 95% CI 1.16 - 1.78) and extra-articular disease (aOR 1.78, 95% CI 1.00 - 3.16). In this model, the triple combination therapy also predicted lower likelihood of DMARD change (aOR 0.30, 95% CI 0.12 - 0.79).Subgroup analyses showed that MTX monotherapy was associated with lower risk of change due to ADR. Combination therapy conferred lower risk of change due to LoE. Poor mental health was associated with change due to ADR, and extra-articular disease, HAQ-disability at baseline, and younger age predicted LoE. CONCLUSIONS: Our findings suggest that non-pharmacological interventions to improve disability and mental health, may reduce initial DMARD treatment failure.
25534420 Risk of venous thromboembolism in patients with rheumatoid arthritis: initiating disease-m 2015 May OBJECTIVES: Recent research suggests that rheumatoid arthritis increases the risk of venous thromboembolism. This study compared the risk of venous thromboembolism in patients with newly diagnosed rheumatoid arthritis initiating a biologic disease-modifying antirheumatic drug (DMARD) with those initiating methotrexate or a nonbiologic DMARD. METHODS: We conducted a population-based cohort study using US insurance claims data (2001-2012). Three mutually exclusive, hierarchical DMARD groups were used: (1) a biologic DMARD with and without nonbiologic DMARDs; (2) methotrexate without a biologic DMARD; or (3) nonbiologic DMARDs without a biologic DMARD or methotrexate. We calculated the incidence rates of venous thromboembolism. Cox proportional hazard models stratified by propensity score (PS) deciles after asymmetric PS trimming were used for 3 pairwise comparisons, controlling for potential confounders at baseline. RESULTS: We identified 29,481 patients with rheumatoid arthritis with 39,647 treatment episodes. From the pairwise comparison after asymmetric PS trimming, the incidence rate of hospitalization for venous thromboembolism per 1000 person-years was 5.5 in biologic DMARD initiators versus 4.4 in nonbiologic DMARD initiators and 4.8 in biologic DMARD initiators versus 3.5 in methotrexate initiators. The PS decile-stratified hazard ratio of venous thromboembolism associated with biologic DMARDs was 1.83 (95% confidence interval [CI], 0.91-3.66) versus nonbiologic DMARDs and 1.39 (95% CI, 0.73-2.63) versus methotrexate. The hazard ratio of venous thromboembolism in biologic DMARD initiators was the highest in the first 180 days versus nonbiologic DMARD initiators (2.48; 95% CI, 1.14-5.39) or methotrexate initiators (1.80; 95% CI, 0.90-3.62). CONCLUSIONS: The absolute risk for venous thromboembolism was low in patients with newly diagnosed rheumatoid arthritis. Initiation of a biologic DMARD seems to be associated with an increased short-term risk of hospitalization for venous thromboembolism compared with initiation of a nonbiologic DMARD or methotrexate.
23945134 Serological identification of fast progressors of structural damage with rheumatoid arthri 2013 Aug 14 INTRODUCTION: Rheumatoid arthritis (RA) patients with structural progression are in most need of immediate treatment to maintain tissue integrity. The serum protein fingerprint, type I collagen degradation mediated by matrix metalloproteinases (MMP)-cleavage (C1M), is a biomarker of tissue destruction. We investigated whether baseline serum C1M levels could identify structural progressors and if the biomarker levels changed during anti-inflammatory treatment with tocilizumab (TCZ). METHODS: The LITHE-biomarker study (NCT00106535, n = 585) was a one-year phase III, double-blind, placebo (PBO)-controlled, parallel group study of TCZ 4 or 8 mg/kg every four weeks, in RA patients on stable doses of methotrexate (MTX). Spearman's ranked correlation was used to assess the correlation between baseline C1M levels and structural progression at baseline and at weeks 24 and 52. Multivariate regression was performed for delta structural progression. Change in C1M levels were studied as a function of time and treatment. RESULTS: At baseline, C1M was significantly correlated to C-reactive protein (P <0.0001), visual analog scale pain (P <0.0001), disease activity score28-erythrocyte sedimentation rate (DAS28-ESR) (P <0.0001), joint space narrowing (JSN) (P = 0.0056) and modified total Sharp score (mTSS) (P = 0.0006). Baseline C1M was significantly correlated with delta-JSN at Week 24 (R² = 0.09, P = 0.0001) and at Week 52 (R² = 0.27, P <0.0001), and with delta-mTSS at 24 weeks (R² = 0.006, P = 0.0015) and strongly at 52 weeks (R² = 0.013, P <0.0001) in the PBO group. C1M levels were dose-dependently reduced in the TCZ + MTX group. CONCLUSIONS: Baseline C1M levels correlated with worsening joint structure over one year. Serum C1M levels may enable identification of those RA patients that are in most need of aggressive treatment TRIAL REGISTRATION: ClinicalTrials.gov: NCT00106535.
24624914 MTHFR functional genetic variation and methotrexate treatment response in rheumatoid arthr 2014 Mar AIM: To date, functional MTHFR SNPs have been tested for their impact on low-dose methotrexate (MTX) response in small rheumatoid arthritis (RA) cohorts. We sought to test their effect in the single largest cohort studied to date, and undertook a meta-analysis utilizing stringent study inclusion criteria. MATERIALS & METHODS: RA patients treated with MTX monotherapy from the Yorkshire Early Arthritis Register (YEAR) were genotyped using RFLP assays, and tested for association with treatment efficacy. Studies for meta-analysis were screened by a set of stringent inclusion criteria. RESULTS & CONCLUSION: rs1801131 and rs1801133 were not associated with response to MTX in the YEAR cohort, nor did they affect the probability of achieving a low disease activity state. A meta-analysis of comparable studies found no association with these SNPs. MTHFR SNPs rs1801131 and rs1801133 are unlikely to have a clinically meaningful effect on the first 6 months of MTX treatment in early RA.
23141718 Meta-analysis of clinical and radiological efficacy of biologics in rheumatoid arthritis p 2013 Jul Our aim was to compare all eight biologics available for rheumatoid arthritis in two patient populations, methotrexate-naive patients and inadequate responders to methotrexate, based on a comprehensive literature review. The five TNFα antagonists, rituximab, abatacept and tocilizumab used with methotrexate were compared to methotrexate monotherapy using the ACR50 response as the primary clinical endpoint and absence of radiographic progression after 1 year as the primary radiological endpoint. Odds ratios (ORs) were computed, as well as the number needed to treat (NNT) to obtain an ACR50 response for each biologic. We included 22 studies. Overall, combined biologic therapy was significantly more effective than methotrexate alone in both the naive group (OR: 2.11; 95% confidence interval [95%CI], 1.85-2.41) and the unresponsive group (OR: 4.82; 95%CI: 3.83, 6.08). Crude NNTs were as follows: etanercept, five in the naive group and three in the unresponsive group; adalimumab, seven and three; infliximab, seven and five; abatacept, seven and four; rituximab, five and five; and tocilizumab and certolizumab, four in the unresponsive group. None of the differences was statistically significant. In the naive group, combined biologic therapy was associated with a higher rate of absence of radiographic progression after 1 year compared to methotrexate alone (OR: 2.19; 95%CI: 1.55-3.08). All biologics had approximately the same efficacy. Methotrexate-naive patients treated with biologics had significantly less radiographic progression than those with cellular therapy.
23415602 Effects of disease modifying anti-rheumatic drugs on subclinical atherosclerosis and endot 2013 Aug OBJECTIVE: The study was designed to explore the effect of disease modifying anti-rheumatic drugs (DMARDs) on synovial inflammation as well as on atherosclerotic indices in patients with early rheumatoid arthritis (RA). METHODS: The study included 35 early RA patients (disease duration <12 months). Inflammatory variables, like erythrocyte sedimentation rate (ESR) and high sensitivity C-reactive protein (hsCRP) were measured. Carotid intima-media thickness (cIMT) and endothelial dependent flow-mediated vasodilatation (ED-FMD) were measured by high-resolution ultrasonography. Disease activity of RA was assessed by disease activity score (DAS28) and quality of life was determined by Health Assessment Questionnaire-Disability Index (HAQ-DI) Score. All the above parameters were assessed both at baseline and follow-up after 1 year. Patients were treated with methotrexate (MTX), hydroxycholoroquine (HCQ) and sulfasalazine (SSZ) depending on their disease activity. RESULTS: After a year of treatment, variables like ESR, hsCRP, DAS28 and HAQ-DI showed significant improvement (p < 0.0001 for each variable). However, there was no such significant change observed in the lipid profile after 1 year from the baseline. Average body mass index (BMI) of patients remained same at the one year follow-up. The cIMT values after 1 year decreased significantly [0.43 ± 0.08mm] from the baseline [0.50 ± 0.16mm] [p = 0.002]. Similarly, in case of FMD%, the post-1-year treatment values [7.57 (4.04-13.03)] improved significantly from the baseline [5.26 (2.9-10.6)] [p = 0.041]. CONCLUSION: Subclinical atherosclerosis and endothelial dysfunction are demonstrable features even in early RA which improved after therapy. Early intervention of RA with DMARDs not only controls the disease but also retards the atherosclerotic progression.
25028384 Effect of human immunodeficiency virus infection on disease activity in rheumatoid arthrit 2014 Aug OBJECTIVE: To determine the effect of human immunodeficiency virus (HIV) infection on disease activity in rheumatoid arthritis (RA). METHODS: A retrospective records review of patients who contracted HIV infection subsequent to RA diagnosis (HIV group), compared to an HIV-negative group of patients with RA (control group), for 28-joint Disease Activity Score (DAS28) scores at initial presentation (T0) and last clinic visit (TL), and at diagnosis of HIV infection (TH) in the HIV group. RESULTS: Of 1712 patients with RA, 85 were HIV-positive (4.9%), 43 of them contracting HIV subsequent to RA diagnosis. The mean (SD) age, RA disease duration, and duration following diagnosis of HIV were 47.1 (10.1), 10.5 (8.4), and 2.9 (2.0) years, respectively, for the HIV group. Both the HIV and control groups showed similar improvement in joint counts and C-reactive protein (CRP) at visit TL, in spite of methotrexate (MTX) being withdrawn in most patients in the HIV group by visit TL (11.6% in the HIV group were still taking MTX vs 83.7% in the control group, p = 0.0002), but a minority (13.9%) had ongoing moderate to high disease activity at visit TL. In the HIV group, the mean DAS28-erythrocyte sedimentation rate (ESR) and DAS28-CRP scores were similar at baseline, but at visits TH and TL the mean DAS28-ESR scores were significantly higher than the mean DAS28-CRP scores (31% and 31.8%, p < 0.0005 and p < 0.004, respectively), mainly resulting from ESR increase following HIV seroconversion. CONCLUSION: Disease activity improved in most patients in the HIV group in spite of stopping the MTX as the "anchor drug." The DAS28-ESR overestimates disease activity compared to the DAS28-CRP in the setting of HIV infection.
23263550 Tc-99 m diethylenetriamine-pentaacetic acid (DTPA): is it reliable for assessment of metho 2013 Dec Methotrexate (MTX) is commonly employed as the initial DMARD used for the treatment of rheumatoid arthritis (RA). We aimed to contribute to the safety profile of MTX by assessing its cumulative effect on renal filtration. A total of 52 RA adult female patients with normal baseline serum creatinine and GFR at the initial diagnosis of the disease were included. Group 1 (G1) included 30 patients (mean age 40.4 ± 4.4 years) on MTX and NSAIDS, while 22 RA patients (mean age 38.5 ± 8.2 years) who received NSAIDs only served as control group (G2). Renal function was assessed by GFR measurement using technetium diethylenetriamine-pentaacetic acid (Tc-99 m DTPA) at a point of the study time corresponding to disease duration. Twenty-one out of thirty (70 %) in G1 showed reduced GFR compared to 6/22 (27.3 %) in G2 (P = 0.007), with 3.3 ± 0.5 % annual reduction in GFR. Reduced GFR in G1 showed significant negative correlation with age (r = -0.396, P = 0.005), MTX cumulative dose (r = -0.263, P = 0.049), MTX-intake duration (r = -0.293, P = 0.031) and NSAIDs-intake duration (r = -0.344, P = 0.014). Low-dose MTX has a slow cumulative effect on renal filtration manifested by GFR reduction overtime that could be monitored by Tc-99 m DTPA.
22915624 Impact of intravenous abatacept on synovitis, osteitis and structural damage in patients w 2013 Aug OBJECTIVES: This randomised, double-blind, placebo-controlled phase IIIb study evaluated the impact of abatacept on MRI pathology as a primary outcome in methotrexate (MTX)-refractory patients with rheumatoid arthritis. METHODS: Patients received intravenous abatacept (∼10 mg/kg) or placebo, on background MTX, for 4 months, followed by an 8-month open-label extension (OLE; all patients received abatacept plus MTX). Patients had 1.5T MRI with intravenous contrast at baseline, Months 4 and 12; wrist synovitis (three locations assessed), and wrist and hand (15 and eight locations assessed, respectively) osteitis and erosion were scored using OMERACT-RAMRIS. RESULTS: 26/27 abatacept- and 23/23 placebo-randomised patients completed Month 4 and entered the OLE; 26 and 21 completed Month 12. The primary endpoint was not achieved; mean change (SD) from baseline in synovitis was -0.44 (1.47) for abatacept versus 0.52 (1.38) for placebo (p=0.103) at Month 4. For mean change in synovitis adjusted for baseline score (sensitivity analysis), the difference between groups was -0.69, p=0.078. Adjusted mean changes (SE) in osteitis and erosion were -1.94 (0.86) and 0.45 (0.43) for abatacept, and 1.54 (0.90) and 0.95 (0.45) for placebo. Further MRI improvements were observed up to Month 12 for abatacept and from Months 4 to 12 for placebo-treated patients switched to abatacept at Month 4. Clinical efficacy was shown with abatacept and sustained to Month 12. CONCLUSIONS: Despite small patient numbers, MRI detected structural and synovial benefit, sustained to Month 12 in abatacept+MTX-treated patients, and improvements in structural and inflammatory outcomes for placebo+MTX-treated patients following addition of abatacept. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT00420199.
24931951 Clinical and serological predictors of remission in rheumatoid arthritis are dependent on 2014 Jul OBJECTIVE: Early intensive treatment is now the cornerstone for the management of rheumatoid arthritis (RA). In the era of personalized medicine, when treatment is becoming more individualized, it is unclear from the current literature whether all patients with RA benefit equally from such intensive therapies. We investigated the benefit of different treatment regimens on remission rates when stratified to clinical and serological factors. METHODS: The Combination Anti-rheumatic Drugs in Early Rheumatoid Arthritis (CARDERA) trial recruited patients with RA of less than 2 years' duration who had active disease. The trial compared 4 treatment regimens: methotrexate monotherapy, 2 different double therapy regimens (methotrexate and cyclosporine or methotrexate and prednisolone) and 3-drug therapy. Clinical predictors included age, male sex, and tender joint count (TJC) and serological biomarkers included rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA). RESULTS: Patients who were male, over 50 years, had ≥ 6 TJC, were RF-IgM-positive, or ACPA-positive were more likely to achieve remission at 24 months using 3-drug therapy compared to monotherapy (OR 2.99, 4.95, 2.71, 2.54, and 3.52, respectively). There were no differences in response to monotherapy and 3-drug therapy if patients were female, under 50 years, had < 6 TJC, or were seronegative. CONCLUSION: Early intensive regimens have become the gold standard in the treatment of early RA. Our study suggests that this intensive approach is only superior to monotherapy in certain subsets of patients. Although these are unlikely to be the only predictors of treatment response, our study brings us a step closer to achieving personalized medicine in RA.
25084201 Polymorphisms in genes involved in the mechanism of action of methotrexate: are they assoc 2014 Jun BACKGROUND: Methotrexate (MTX) is the first-line treatment option for newly diagnosed rheumatoid arthritis (RA) patients. However, 50-70% of the patients respond to treatment and 30% suffer toxicity. AIM: To identify pharmacogenetic markers of outcome in RA patients treated with MTX. PATIENTS & METHODS: We analyzed 27 genetic variants in DHFR, TYMS, MTHFR, ATIC and CCND1 genes. RESULTS: We included 124 RA patients treated with MTX monotherapy. In multivariate analyses two variants in the MTHFR gene were associated with response, rs17421511 (p = 0.024) and rs1476413 (p = 0.0086), as well as one in the DHFR gene, rs1643650 (p = 0.026). The ATIC rs16853826 variant was associated with toxicity (p = 0.039). CONCLUSION: MTHFR, DHFR and ATIC genetic variants can be considered as pharmacogenetic markers of outcome in RA patients under MTX monotherapy.
23319067 Functional disability can deteriorate despite suppression of disease activity in patients 2013 Nov OBJECTIVE: To analyze the relationship between the progression of disability and disease activity in patients with rheumatoid arthritis (RA) in daily practice. METHODS: Patients from an observational cohort, IORRA, who completed surveys during 2009-2011 were eligible. Linear regression of disease activity score 28 (DAS28), Japanese version of Health Assessment Questionnaire (J-HAQ), and EQ-5D from baseline were calculated, and the angles of the regression lines were designated DAS28 slope, J-HAQ slope, and EQ-5D slope, respectively, in each patient; averages were compared between treatment groups. RESULTS: A total of 5,038 patients [84.0% female, mean age 59.4 (SD 13.1) years, disease duration 13.2 (9.6) years, DAS28 3.29 (1.14), and J-HAQ 0.715 (0.760)] were analyzed. The average DAS28 slope indicated improvement in all groups, whereas J-HAQ slopes were negative in patients on methotrexate (MTX), biologics, combination biologics/disease-modifying antirheumatic drugs (DMARDs), and combination biologics/MTX at baseline, but positive in patients on prednisolone >5 mg/day [0.010 (0.153)] and not on MTX at baseline [0.007 (0.122)], representing a worsening of disability. CONCLUSION: There is some disparity between improvement of disease activity and progression of disability, suggesting that quality of remission must be considered.