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ID PMID Title PublicationDate abstract
27885916 ATIC missense variant affects response to methotrexate treatment in rheumatoid arthritis p 2016 Dec AIM: The study was aimed at investigation of several gene variants of folate pathway enzymes for their potential association with methotrexate (MTX) treatment response in patients with rheumatoid arthritis. PATIENTS & METHODS: Four hundred and twenty two Caucasian patients were classified as good or poor responders, and subsequently genotyped for common SNPs in DHFR, FPGS and ATIC genes. RESULTS: No significant differences were observed in case of DHFR and FGPS SNPs. As for ATIC rs2372536 (Thr116Ser), GG minor genotype was significantly associated with good response to MTX (OR: 2.40; 95% CI: 1.30-4.42; p = 0.005), which was confirmed by multivariate analysis. CONCLUSION: The results of the study suggest that ATIC missense rs2372536 SNP may influence response to MTX therapy in rheumatoid arthritis patients.
27721549 Hepatic and hematological adverse effects of long-term low-dose methotrexate therapy in rh 2016 Sep OBJECTIVES: Methotrexate (MTX) is the most commonly used cost-effective disease-modifying antirheumatoid drug (DMARD). Its main dose-limiting adverse effects are hepatic and hematopoietic. This cross-sectional, observational study evaluated the prevalence of hepatic and hematological adverse effects with long-term low-dose MTX therapy. MATERIALS AND METHODS: Rheumatoid arthritis (RA) patients taking ≤15 mg/week MTX for at least 2 years were enrolled from the rheumatology outpatient department. Demographic, disease, drug treatment profiles, and hematological and hepatic enzyme levels were noted. RESULTS: Of the 204 patients enrolled, the frequency of raised alanine transaminase level (≥3-fold rise above the upper limit of normal) was 6.37% (95% confidence interval of 3.76-10.59) including two biopsy-proven hepatic fibrosis cases. About 5.4% had severe anemia (<8 g/dl) and 4.4% had leukopenia. CONCLUSION: Long-term low-dose MTX is safe in RA patients in the Indian population. The patterns of adverse effects were similar to those documented in earlier studies. However, our study results suggest that disease duration, cumulative MTX dose, concomitant DMARD intake are not risk factors associated with hepatic or hematological adverse effects.
25994819 Existing joint erosions increase the risk of joint space narrowing independently of clinic 2015 May 21 INTRODUCTION: Clinical synovitis is often associated with damage to bone and cartilage. Previous data have suggested that joint erosions (JE) are more prevalent than joint space narrowing (JSN) and that the two processes are partly independent of each other. The objective of this study was to evaluate whether the presence of JE in an individual joint can lead to development of JSN and if existing JSN leads to new onset of JE, in the absence of synovitis. METHODS: The Prospective Multi-Centre Randomised, Double-Blind, Active Comparator-Controlled, Parallel-Groups Study Comparing the Fully Human Monoclonal Anti-TNFα Antibody Adalimumab Given Every Second Week With Methotrexate Given Weekly and the Combination of Adalimumab and Methotrexate Administered Over 2 Years in Patients With Early Rheumatoid Arthritis (PREMIER) enrolled early rheumatoid arthritis (RA) patients who were randomized to one of three treatments: methotrexate (MTX), adalimumab (ADA), or ADA + MTX. All evaluable joints with JE and JSN measures at 26 and 52 weeks and synovitis assessments from week 26 to 52 were included. Synovitis was assessed every 2-8 weeks by swollen joint counts between weeks 26 and 52. Radiographs were taken at week 26 and 52. Two readers, blinded to time and sequence, scored 14 bilateral joints individually for JE and JSN. Multivariate logistic modeling was used to characterize the dependence of JE/JSN onset at 52 weeks. Analyses were performed based on treatment arm and were also performed within individual joints. RESULTS: JE and swelling were independently and comparably associated with onset of JSN at week 52. Assessment by individual joints indicated that existing JE, independent of swelling, was significantly associated with JSN onset in higher proportions of metatarsophalangeal (MTP; 7/10) than proximal interphalangeal (PIP; 1/8) or metacarpophalangeal (MCP; 1/10) joints. Treatment with ADA + MTX prevents JE/JSN progression independently of its ability to suppress synovitis and limits JE/JSN onset and progression in joints with existing damage. CONCLUSIONS: Existing JE predisposes individual joints to development of JSN independently of synovitis in the same joint. Weight-bearing MTP joints with JE may be at increased risk for JSN when compared with MCPs and PIPs. TRIAL REGISTRATION: Clinicaltrials.gov NCT00195663. Registered 13 September 2005.
27829394 The Scottish Early Rheumatoid Arthritis (SERA) Study: an inception cohort and biobank. 2016 Nov 9 The Scottish Early Rheumatoid Arthritis (SERA) study is an inception cohort of rheumatoid (RA) and undifferentiated arthritis (UA) patients that aims to provide a contemporary description of phenotype and outcome and facilitate discovery of phenotypic and prognostic biomarkers METHODS: Demographic and clinical outcome data are collected from newly diagnosed RA/UA patients every 6 months from around Scotland. Health service utilization data is acquired from Information Services Division, NHS National Services Scotland. Plain radiographs of hands and feet are collected at baseline and 12 months. Additional samples of whole blood, plasma, serum and filtered urine are collected at baseline, 6 and 12 months RESULTS: Results are available for 1073 patients; at baseline, 76 % were classified as RA and 24 % as UA. Median time from onset to first review was 163 days (IQR97-323). Methotrexate was first-line DMARD for 75 % patients. Disease activity, functional ability and health-related quality of life improved significantly between baseline and 24 months, however the proportion in any employment fell (51 to 38 %, p = 0.0005). 24 % patients reported symptoms of anxiety and/or depression at baseline. 35/391 (9 %) patients exhibited rapid radiographic progression after 12 months. The SERA Biobank has accrued 60,612 samples CONCLUSIONS: In routine care, newly diagnosed RA/UA patients experience significant improvements in disease activity, functional ability and health-related quality of life but have high rates of psychiatric symptoms and declining employment rates. The co-existence of a multi-domain description of phenotype and a comprehensive biobank will facilitate multi-platform translational research to identify predictive markers of phenotype and prognosis.
25941102 Optimizing perioperative outcomes for older patients with rheumatoid arthritis undergoing 2015 May Patients with rheumatoid arthritis continue to undergo arthroplasty despite widespread use of potent disease-modifying drugs (DMARDs), including the biologic tumor necrosis-α inhibitors. In fact, over 80 % of RA patients are taking DMARDs or biologics at the time of arthroplasty. While many RA-specific factors including disease activity and disability may contribute to the increase in infection in RA patients undergoing arthroplasty, immunosuppressant medications may also play a role. As the age of patients with RA undergoing arthroplasty is rising, and the incidence of arthroplasty among the older population is increasing, optimal perioperative management of DMARDs and biologics in older patients with RA is an increasing challenge. Although evidence is sparse, most evidence supports withholding tumor necrosis-α inhibitors and other biologics prior to surgery based on the dosing interval, and continuing methotrexate and hydroxychloroquine through the perioperative period. There is no consensus regarding leflunomide, and rituximab risk does not appear related to the interval between infusion and surgery. This paper reviews arthroplasty outcomes including complications in patients with RA, and discusses the rationale for strategies for the optimal medication management of DMARDs and biologics in the perioperative period to minimize complications and improve outcomes.
27825567 Prevalence of rheumatoid arthritis in the French West Indies: Results of the EPPPRA study 2017 Jul OBJECTIVES: Studies suggest that rheumatoid arthritis (RA) is less frequent in African populations. However, no recent precise data exists for Afro-Caribbeans. The EPPPRA project is a prospective epidemiological survey to describe prevalence and clinical aspects of RA in the French West Indies (Martinique, Guadeloupe, French Guiana). METHODS: EPPPRA involved all rheumatologists from the French West Indies who included all patients with a known clinical diagnosis of RA, during a one-year period. We outline here results for Martinique. RESULTS: EPPPRA estimated an overall world age-standardized prevalence of RA at 0.10% [95% CI 0.09% to 0.11%] in Martinique, with a high female predominance (88.1%) and 93.1% of self-reported Afro-Caribbeans. Mean age at diagnosis was 49.6±16.0 years. A majority of subjects presented at least 4 criteria points from the 1987 American College of Rheumatology (ACR) classification (94.4%) and at least 6 points (78.2%) from the 2010 ACR/European League Against Rheumatism (EULAR) classification. A high immune seropositivity rate was highlighted (84.2%). Despite functional impact observed in 40.5% of patients, 71.4% presented a low disease activity level. Methotrexate was the most common ongoing treatment (73%), followed by biotherapies (24.4%). Numerous patients (68.6%) received a steroid regimen. Cardiovascular risk factors were very frequent, contrasting with a very low tobacco use (8.7%), CONCLUSION: This work outlines low standardized prevalence of RA in a French Afro-Caribbean population with specific characteristics (high female predominance, high immune seropositivity, low tobacco use). Despite easy access to care and biotherapies, approximately half of RA patients still present destructive disease with functional impact.
24706006 Current smoking status is a strong predictor of radiographic progression in early rheumato 2015 Aug OBJECTIVES: To study clinical predictors for radiographic progression after 1 year in an early rheumatoid arthritis (RA) trial. METHODS: In the SWEFOT trial population, disease modifying antirheumatic drug (DMARD) naïve RA patients started methotrexate; 3-month responders (DAS28 <3.2) continued (n=147), while non-responders were randomised to addition of sulfasalazine+hydroxychloroquine (n=130) or infliximab (n=128). X-rays were scored by the Sharp-van der Hejde score (SHS) method and radiographic progression was defined as a ≥5 increase after 1 year. Potential baseline predictors of radiographic progression were tested using multivariable logistic regression, adjusted for potential confounders. RESULTS: 79 of 311 patients with available radiographs at baseline and follow-up had radiographic progression. The following baseline parameters were independent predictors of radiographic progression at 1 year: baseline erosions (adjusted OR=2.29, 95% CI 1.24 to 4.24), erythrocyte sedimentation rate (adjusted OR per tertile increase=1.72, 95% CI 1.12 to 2.65) and C-reactive protein (adjusted OR per tertile increase=1.52, 95% CI 1.03 to 2.26). Current smoking was an independent predictor of radiographic progression (adjusted OR=2.17, 95% CI 1.06 to 4.45). These results remained after further adjustment for treatment strategy. Three-dimensional matrix including current smoking status, erosions and C-reactive protein tertiles showed a 12-63% risk gradient from patients carrying none compared with all predictors. Rheumatoid factor (RF)/anti-cyclic citrullinated peptide (anti-CCP) positivity did not significantly predict radiographic progression using SHS increase ≥5 as cut-off. In a secondary exploratory analysis using cut-off >1, both RF and anti-CCP positivity were significant predictors in the unadjusted, but not the adjusted analyses. The other parameters also remained significant using this lower cut-off. CONCLUSIONS: In addition to previously described predictors, we identified smoking as a strong independent risk factor for radiographic progression in early RA. TRIAL REGISTRATION NUMBER: NCT00764725.
26150618 Co-occurrence of rheumatoid arthritis and sarcoidosis. 2015 Jul 6 Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by erosive arthritis. Sarcoidosis is a chronic disease characterised by formation of non-calcified granulomas. Our case, a 35-year-old woman, presented with metacarpophalangeal, proximal interphalangeal (PÄ°P) joints and arthritis of both ankles, of 6-month duration. She had morning stiffness lasting 1 h, restriction of range of motion and erythaema nodosum. Laboratory tests showed elevated acute phase responses and serum ACE levels, and anti-cyclic citrullinated peptide antibody positivity. There was periarticular osteoporosis on her hand and wrist on direct X-rays and hilar lymphadenopathy on her thorax CT. The pathological result of endobronchial ultrasound biopsy showed non-calcified granuloma congruent with sarcoidosis. According to clinical, laboratory and histopathological evaluation, the patient was diagnosed with RA and sarcoidosis. Corticosteroids and methotrexate were started, and on her sixth month of follow-up, her clinical and laboratory findings and lymphadenopathies on CT had regressed. The clinical follow-up continues; the patient appears to be in clinical remission.
26466969 Immunological evaluation of rheumatoid arthritis patients treated with itolizumab. 2016 Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical samples taken from 30 patients enrolled in a clinical trial. T and B cell subpopulations were measured at different time points of the study. Plasma cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. The combined treatment of itolizumab and methotrexate led to a reduction in the frequency of T cell subpopulations, and plasma levels of proinflammatory cytokines showed a significant decrease up to at least 12 weeks after treatment ended. No anti-idiotypic antibody response was detected. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease.
25800214 Clocking in: chronobiology in rheumatoid arthritis. 2015 Jun Circadian rhythms are of crucial importance for cellular and physiological functions of the brain and body. Chronobiology has a prominent role in rheumatoid arthritis (RA), with major symptoms such as joint pain and stiffness being most pronounced in the morning, possibly mediated by circadian rhythms of cytokine and hormone levels. Chronobiological principles imply that tailoring the timing of treatments to the circadian rhythm of individual patients (chronotherapy) could optimize results. Trials of NSAID or methotrexate chronotherapy for patients with RA suggest such an approach can improve outcomes and reduce adverse effects. The most compelling evidence for RA chronotherapy, however, is that coordinating the timing of glucocorticoid therapy to coincide with the nocturnal increase in blood IL-6 levels results in reduced morning stiffness and pain compared with the same glucocorticoid dose taken in the morning. Aside from optimizing relief of the core symptoms of RA, chronotherapy might also relieve important comorbid conditions such as depression and sleep disturbances. Surprisingly, chronobiology is not mentioned in official guidelines for conducting RA drug registration trials. Given the imperative to achieve the best value with approved drugs and health budgets, the time is ripe to translate the 'circadian concept' in rheumatology from bench to bedside.
26354025 Efficacy of etanercept for treating the active rheumatoid arthritis: an updated meta-analy 2016 Nov AIM: To evaluate the efficacy of etanercept (ETA) for treating active rheumatoid arthritis (RA) compared to placebo or methotrexate (MTX). METHODS: We searched Medline, Cochrane Library and Wiley databases. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to compare efficacy. RESULTS: In total, 12 studies with 3878 active RA patients (including 2046 patients treated with ETA and 1832 patients treated with placebo or MTX) were included. The overall RRs in ACR20, 50 and 70 (20%, 50%, 70% improvement based on the criteria of American Rheumatism Association) were 2.10 (95% CI: 1.45-3.02, P < 0.0001), 2.87 (95% CI: 1.66-4.97, P = 0.0002) and 2.16 (95% CI: 1.49-3.13, P < 0.0001) within 24 weeks, respectively and were 1.19 (95% CI: 1.11-1.28, P < 0.00001), 1.37 (95% CI: 1.22-1.53, P < 0.00001) and 1.57 (95% CI: 1.28-1.92, P < 0.00001) within 1-3 years, respectively. Further, the overall RRs of 25 mg versus 10 mg ETA twice weekly in ACR20, 50 and 70 were 1.10 (95% CI: 1.02-1.19, P < 0.02), 1.37 (95% CI: 0.98-1.92, P < 0.07) and 1.27 (95% CI: 1.02-1.58, P < 0.03), respectively. CONCLUSIONS: In active RA patients treated with ETA, there was significantly higher efficacy compared to the treatment of placebo or MTX. High doses of ETA were more effective for active RA patients.
26097059 Epidemiology and Treatment of New-Onset and Established Rheumatoid Arthritis in an Insured 2015 Dec OBJECTIVE: To investigate the epidemiology and treatment of rheumatoid arthritis (RA) in a population broadly representative of employed adults in the US, using a retrospective cohort design. METHODS: Incident and prevalent RA cohorts were defined from a sample of 4.66 million adults with complete followup data from the period of January 2005 through September 2008 in the Pharmetrics medical claims database. Demographics, comorbidity, and medical therapies were summarized using descriptive statistics. RESULTS: Median duration in the database was 5.7 years. Age- and sex-adjusted incidence in 2006 was 0.71 per 1,000 persons at risk (n = 3,992) and prevalence in 2005 was 0.63% (n = 30,530). Within 12 months after diagnosis, 65%, 64%, and 20% of the incident cohort had been prescribed corticosteroids, nonbiologic disease-modifying antirheumatic drugs (DMARDs), and tumor necrosis factor (TNF) inhibitors, respectively. Median time to first anti-TNF prescription was 6 months; 31% switched to a second drug and 15% to a third. An aggressive subcohort (11% of incident patients) received more DMARDs (83%) and TNF inhibitors (43%), and was more likely to switch. Twenty-eight percent of incident patients received only symptomatic therapy over a minimum of 1.75 years of followup; these patients were older with more comorbidities and contraindications to methotrexate. CONCLUSION: In this insured population-based cohort, only two-thirds of newly diagnosed RA patients were prescribed a DMARD in year 1 and 28% received no antirheumatic therapy. Although limited by lack of clinical information and by left-censoring, administrative databases capture clinical practice and suggest that gaps exist in treatment options available to a significant number of patients.
26017232 Chikungunya infection in the general population and in patients with rheumatoid arthritis 2015 Jul Chikungunya infection is a febrile illness, which currently is afflicting the Caribbean islands including the Dominican Republic. We would like to report our experience with Chikungunya-related musculoskeletal manifestations in our arthritis clinics in the Dominican Republic. A total of 514 patients presented for the first time to our arthritis clinic exhibiting musculoskeletal manifestations, 473/514 (92%) exhibiting symmetric polyarthralgias, 344/514 (67%) arthritis, and 385 (75%) skin rash. The great majority 457.46 (89%) exhibited very good clinical response to nonsteroidal anti-inflammatory drugs (NSAIDs), 370 (72%) require low-dose steroids, and only 5 patients (0.97%) required methotrexate therapy. In addition, of a total of 328 patients with rheumatoid arthritis on biological treatment, 53 exhibited Chikungunya-related musculoskeletal manifestations; 51/53 (96.2%) exhibited symmetric polyarthralgias, 25/53 (47.1%) arthritis, and 13/53 (24.5%) tendinopathy. Of most patients, 51/53 responded to NSAIDs, of which, 23 patients only responded partially, and in total 25 (47.1%) required low-dose steroids. Disease-modifying antirheumatic drug (DMARD) therapy including biologics remained unchanged in this population.
26539002 Effects of Methotrexate on Carotid Intima-media Thickness in Patients with Rheumatoid Arth 2015 Nov The purpose of this study was to evaluate the effects of rheumatoid arthritis (RA) and antirheumatic drugs on atherosclerosis by comparing carotid intima-media thickness (CIMT) as an indicator for cardiovascular diseases (CVD). This study included 44 female RA patients who met the 2010 ACR/EULAR criteria and age-matched 22 healthy females. CIMT was measured on both carotid arteries using a B-mode ultrasound scan. The mean value of both sides was taken as the CIMT of the subject. The CIMT was evaluated according to the use of drugs, disease activity and CVD risk factors in RA patients as a case-control study. Higher CIMT was observed in RA patients as compared with healthy subjects (0.705 ± 0.198 mm, 0.611 ± 0.093 mm, respectively, P < 0.05). With adjustment for the CVD risk factors, disease activity and the use of anti-rheumatic drugs, methotrexate (MTX) only showed a favorable effect on CIMT in RA. A significantly lower CIMT was observed in RA with MTX as compared with RA without MTX (0.644 ± 0.136 mm, 0.767 ± 0.233 mm, respectively, P < 0.05). The effects were correlated with MTX dosage (β = -0.029, P < 0.01). The use of MTX should be considered in high priority not only to control arthritis but also to reduce the RA-related CVD risk to mortality.
27974101 Response to methotrexate predicts long-term mortality of patients with rheumatoid arthriti 2017 May OBJECTIVES: To assess if there is a correlation between the degree of response to treatment with methotrexate (MTX) and long-term mortality in a cohort of patients with rheumatoid arthritis (RA) established in Germany in the early eighties. METHODS: RA patients who had started MTX treatment between 1980 and 1987 were included. One year after baseline, the treatment response was evaluated. Responders were defined as patients with at least 20% decline in the swollen joint count (out of 32 joints) and the ESR with a prednisone dosage <5 mg/day. Thereafter, assessments were performed at 10, 18, and 30 years after baseline. Standardised mortality ratios (SMR) were calculated, Cox regression and logistic regression were performed. RESULTS: The cohort comprised 271 patients. In 2015, about 30 years after the initiation of MTX therapy, 185 patients (68%) were deceased, 52 (19%) lost to follow-up and 34 alive. The response after the first year of MTX treatment was the strongest predictor of survival with a hazard ratio of 0.44 (95% confidence interval [CI]: 0.30-0.65). However, even responders still had an SMR of 1.37 (95% CI 1.31-1.65), but this was much worse for non-responders who had an SMR of 4.22 (95% CI 3.13-5.56). Using Cox regression analysis no difference was detected between responders with more than 50% improvement (38% of all patients) and those with 20-50% improvement (28%). CONCLUSIONS: The predictive value of a response to one year of MTX therapy for long-term mortality of RA patients is independent of the degree of response.
26587852 Adherence to Anti-Tumor Necrosis Factor Therapy Administered Subcutaneously and Associated 2015 Dec BACKGROUND: Adherence to biologic therapy is relatively poorly studied in rheumatoid arthritis (RA) because many of the studies have investigated the drug persistence, which represents only a surrogate of adherence. OBJECTIVES: The aims of this study were to determine the extent of adherence in RA patients with subcutaneously administered anti-tumor necrosis factor methotrexate agents and to identify the risk factors for nonadherence. METHODS: A cohort of RA patients who started a subcutaneous anti-tumor necrosis factor treatment were enrolled. After 12 months of treatment, all patients completed the 4-item Morisky Medication Adherence Scale questionnaire. Associations between beliefs and nonadherence and the influence of demographic, clinical, and radiographic features were assessed using logistic regression model. RESULTS: A total of 209 (80.4%) of the 260 patients were included in the analyses. Forty-three of 209 patients were considered nonadherent to their medication (20.6%) according to the 4-item Morisky Medication Adherence Scale. More than half (53.1%) of patients showed at least 1 form of nonadherent behavior.The logistic model showed that low disease activity (P = 0.003), higher patient-physician discordance ratings (P = 0.012), older age (P = 0.041), and a high number of comorbid conditions (P = 0.011) were significantly associated with increased likelihood of nonadherence. CONCLUSIONS: The overall nonadherence with subcutaneous biologic therapy is relatively high among RA patients and should be taken into account when a patient's response to treatment is unsatisfactory.
26222244 The role of methotrexate and low-dose prednisolone on adiponectine levels and insulin resi 2016 Jul AIM: Insulin resistance (IR) plays an important role in the development of cardiovascular events in rheumatoid arthritis (RA) patients. Adiponectin influences insulin sensitivity but its impact on IR in RA patients remains unclear. The present study aims to investigate the role of methotrexate (MTX) and low doses of prednisolone (LDP) on IR and adiponectin levels in RA patients who are naïve to disease-modifying antirheumatic drugs (DMARDs), as well as determining the relationship between disease activity, acute phase response, IR and adiponectin levels in patients with RA. METHODS: Sixty-five RA patients naïve to DMARDs and prednisolone were involved in this study. The medication for RA patients was standardized for MTX and prednisolone. Body mass index, acute phase response reactants, 28-joint-count disease activity score, fasting blood glucose, serum cholesterol levels, insulin levels and adiponectin levels were measured in all RA patients both at the baseline and 3 months after the onset of the study. RESULTS: Adiponectin levels in the third month of the therapy with MTX and LDP were significantly increased in patients with RA (P = 0.03). Insulin resistance tended to decrease in the third month of the treatment, which achieved no statistical significance. CONCLUSION: Increased levels of adiponectin due to MTX and LDP could be related to the decrease in homeostasis model assessment insulin resistance (HOMA-IR) in RA patients. This, in turn, could prove advantageous for cardiovascular conditions in RA.
27239921 [Relationship between matrix metalloproteinase-3 levels and articular destructive changes 2016 AIM: To estimate a relationship between matrix metalloproteinase-3 (MMP-3) levels and articular radiographic changes in early and extended rheumatoid arthritis (RA); to analyze the role of this biomarker in predicting the progression of joint destruction in RA. SUBJECTS AND METHODS: Forty-five patients with early RA and 42 with extended RA were examined. Radiography of the hands and distal feet was performed before and one year after therapy. Serum MMP-3 levels were measured by an enzyme immunoassay prior to and 12 and 24 weeks after treatment. RESULTS: After 52 weeks, in the early RA group, 16 patients continued monotherapy with methotrexate (MT); because of its inefficiency, 29 additionally received a biological agent in different follow-up periods. The extended RA group took tocilizumab for 24 weeks, then the drug was discontinued and the patients continued the former therapy with disease-modifying antirheumatic drugs, nonsteroidal anti-inflammatory drugs, and glucocorticosteroids. One year later, radiographic progression was recorded in 20.5 and 22.5% of the patients with early and extended RA, respectively. ROC analysis indicated that in the early RA group the MMP-3 level of more than 34.3 ng/ml at 12 weeks of MT therapy was associated with the radiographic progression of articular destructive changes after 52 weeks of therapy (the area under the curve (AUC) was 0.7; 95% confidence interval (CI) 0.46 to 0.93). In the patients with extended RA, the baseline MMP-3 levels of ≤51.3 ng/ml was related to no radiographic progression following 52 weeks (AUC, 0.587; 95% CI 0.33 to 0.84). CONCLUSION: MMP-3 may be regarded as an early marker for joint destruction in RA. The determination of MMP-3 level with other immunological markers may be useful to identify a group of patients who have a potentially severer disease course and need more intensive therapy.
26314492 Influence of MTHFR C677T polymorphism on methotrexate monotherapy discontinuation in rheum 2015 Sep OBJECTIVES: Methotrexate (MTX) is the most widely prescribed drug for rheumatoid arthritis (RA) patients, but 45% of them discontinue therapy within two years, either due to inefficacy or toxicity. Several authors have reported contradictory results related to C677T polymorphism in the MTHFR gene and response to MTX in RA. The purpose of this study was to further explore this genotype-response association in a European RA population. METHODS: This retrospective longitudinal study included a total of 269 RA patients from Italy and Hungary, of whom 73.2% had available data on MTX treatment (197 patients). C677T polymorphism (rs1801133) was genotyped by quantitative PCR using TaqMan assays. Genotype association analysis and Kaplan-Meier method were used for statistical comparisons between patients continuing and patients who abandoned MTX treatment. RESULTS: A total of 85 out of the 197 RA patients (43%) abandoned MTX treatment by the time of analysis. No significant genotype-MTX discontinuation association was found for the overall population, either at the end of the study (p=0.375), or during the follow-up (p=0.324). When the analysis was restricted to the 68 patients on MTX monotherapy, a borderline association (OR 3.15, 95% CI 0.93-10.67, p=0.057) was noted with the recessive genetic model. In agreement with that, a Kaplan-Meier analysis showed a significantly shorter time-to-discontinuation of MTX monotherapy for homozygous carriers of the T-allele (p=0.042). CONCLUSIONS: These results demonstrate that the C677T polymorphism in the MTHFR gene is involved in MTX monotherapy discontinuation in a multicentre European patient cohort, confirming previous results.
25108207 Association between serum uric acid and inflammation in rheumatoid arthritis: perspective 2015 Jan 1 BACKGROUND: The association between serum uric acid concentrations and inflammation in patients with rheumatoid arthritis (RA) has been still controversial. METHODS: A total of 172 patients with RA who added leflunomide to methotrexate (MTX) in their treatment regimens were enrolled in this study. Twenty-seven RA patients taking MTX without leflunomide were also recruited in order to assess the fractional excretion of uric acid (FEUA). RESULTS: After leflunomide therapy for an average of 4.6months, serum uric acid concentrations had significantly decreased compared to baseline concentrations (p<0.001). Patients treated with a combination of MTX and leflunomide (n=23) showed higher FEUA than those treated with only MTX (n=27) (p=0.007). Differences in serum uric acid concentrations after leflunomide therapy were significantly associated with those in serum creatinine concentrations (B coefficient=3.081, p<0.001), but not with those in acute phase reactants including ESR and CRP. CONCLUSION: This study determined that leflunomide reduced serum uric acid concentrations through increased urinary excretion of uric acid, which might not reflect changes in disease activity status in RA. This implies that uric acid may not influence systemic inflammation in RA.