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

ID PMID Title PublicationDate abstract
23213004 Clinical and ultrasound-based composite disease activity indices in rheumatoid arthritis: 2013 Jun OBJECTIVE: To evaluate the metrologic properties of composite disease activity indices in rheumatoid arthritis (RA), utilizing information derived from clinical, gray-scale (GS), and power Doppler (PD) ultrasound examinations, and to assess the classification of patients according to disease activity using such indices. METHODS: This ancillary study utilized data from a multicenter, prospective, randomized, parallel-group study conducted in subjects with moderate RA randomized to receive etanercept and methotrexate (ETN + MTX) or usual care (various disease-modifying antirheumatic drugs [DMARDs]). In multimodal indices, the 28 swollen joint count was either supplemented or replaced by clinically nonswollen joints in which the presence of synovitis was detected either by GS and/or PD and was calculated according to the Disease Activity Score in 28 joints (DAS28) or the Simplified Disease Activity Index (SDAI). Reliability, external validity, and discriminative capacity were calculated at baseline/screening by intraclass correlation coefficient, Pearson's correlation, and standardized response mean, respectively. RESULTS: Data from 62 patients (mean ± SD age 53.8 ± 13.2 years, mean ± SD disease duration 8.8 ± 7.7 years, mean ± SD disease activity 4.6 ± 0.5 [DAS28] and 20.9 ± 5.9 [SDAI]) were analyzed, with 32 receiving ETN + MTX and 30 receiving DMARDs. The metrologic properties were at least as good for GS- and/or PD-based indices as for their clinical counterparts. Using GS- and PD-supplemented indices, an additional 67.8% and 32.3% of patients (DAS28-derived and SDAI-derived indices, respectively) could be classified as having high disease activity at the screening visit. CONCLUSION: Multimodal indices incorporating ultrasound and clinical data had similar metrologic properties to their clinical counterparts; certain indices allowed for a significantly larger number of patients to be classified to either high or moderate disease activity at the screening visit.
24190155 Sudden glottic stenosis caused by cricoarytenoid joint involvement due to rheumatoid arthr 2013 A woman with rheumatoid arthritis (RA) experienced glottic stenosis approximately two months after switching from etanercept to tocilizumab. Cricoarytenoid joint (CAJ) arthritis due to RA was diagnosed. An awake tracheostomy saved the relievable airway, and the administration of methylprednisolone and infliximab ameliorated the flare-up and glottic stenosis. A follow-up examination revealed the recovery of the patient's normal voice and good control of RA with infliximab and methotrexate. Although general physicians do not frequently encounter patients with symptomatic CAJ arthritis, this condition should be considered as it can be life-threatening. Therefore, when detected, it should be diagnosed and treated immediately.
25530330 Late-onset rheumatoid arthritis in the Counties Manukau District Health Board region of Ne 2014 Dec 19 AIM: The aim of this retrospective study was to investigate whether there are differences in the early treatment of Rheumatoid Arthritis (RA) depending on the age of the patient at diagnosis. METHODS: The electronic records of 127 newly diagnosed RA patients presenting to the Counties Manukau District Health Board Rheumatology outpatient clinic between January 2008 and December 2010 were reviewed. Demographics, disease severity, relevant investigations, and medication use were analysed using Pearson's Chi squared test, Fisher's exact test and t-test. RESULTS: The cohort included 32 aged greater than or equal to 60 years with Late Onset RA (LORA) and 95 aged <60 years with Young Onset RA (YORA). No significant differences in baseline disease severity, disease modifying anti-rheumatic drug or prednisone use rates were observed between the LORA and YORA groups, with methotrexate use rates of 26/32 (81.25%) and 74/95 (77.89%) respectively. Nonsteroidal anti-inflammatory (NSAID) rate was significantly lower (p=0.013) in the LORA group 14/32 (43.75%) compared to the YORA group 65/95 (68.42%), reflecting an awareness of the adverse effects of these drugs in an older population. CONCLUSION: Patients with new onset rheumatoid arthritis at our institution received similar disease modifying anti-rheumatic drug treatment irrespective of their age.
23436821 Sustained beneficial effects of a protocolized treat-to-target strategy in very early rheu 2013 Aug OBJECTIVE: Treat-to-target (T2T) leads to improved clinical outcomes in early rheumatoid arthritis (RA). The question is whether these results sustain in the long term. Our objective was to investigate the 3-year results of a protocolized T2T strategy in daily clinical practice. METHODS: In the Dutch Rheumatoid Arthritis Monitoring remission induction cohort, patients newly diagnosed with RA were treated according to a T2T strategy aimed at remission (Disease Activity Score in 28 joints [DAS28] <2.6). Patients were treated with methotrexate, followed by the addition of sulfasalazine, and exchange of sulfasalazine with anti-tumor necrosis factor α agents in case of failure. Primary outcomes were disease activity, Health Assessment Questionnaire (HAQ) score, Short Form 36 physical component summary (PCS) and mental component summary (MCS) scores, and the Sharp/van der Heijde score (SHS) after 3 years. Secondary outcomes were sustained DAS28 remission (≥6 months) and remission according to the provisional American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) definition. RESULTS: After 3 years (n = 342), 61.7% of patients were in DAS28 remission and 25.3% met the provisional ACR/EULAR definition of remission. Sustained remission was experienced by 70.5%, which in the majority was achieved with conventional disease-modifying antirheumatic drugs only. The median scores were 0.4 (interquartile range [IQR] 0.0-1.0) for the HAQ, 45.0 (IQR 38.4-53.2) for the PCS, 53.1 (IQR 43.2-60.8) for the MCS, and 6.0 (IQR 3.0-13.0) for the total SHS. CONCLUSION: In very early RA, T2T leads to high (sustained) remission rates, improved physical function and health-related quality of life, and limited radiographic damage after 3 years in daily clinical practice.
25391609 Three decades of low-dose methotrexate in rheumatoid arthritis: can we predict toxicity? 2014 Dec Methotrexate (MTX) is the anchor disease-modifying antirheumatic drug (DMARD) in rheumatoid arthritis (RA) treatment. It is used in monotherapy and/or in combination with other synthetic or biological DMARDs, and is known to have the best cost-effectiveness and efficacy/toxicity ratios. However, toxicity is still a concern, with a significant proportion of patients interrupting long-term treatment due to the occurrence of MTX-related adverse drug reactions (ADRs), which are the main cause of drug withdrawal. Despite the extensive accumulated experience in the last three decades, it is still impossible in routine clinical practice to identify patients prone to develop MTX toxicity. While clinical and biological variables, including folate supplementation, partially help to minimize MTX-related ADRs, the advent of pharmacogenomics could provide further insight into risk stratification and help to optimize drug monitoring and long-term retention. In this paper, we aimed to review and summarize current data on low-dose MTX-associated toxicity, its prevention and predictors, keeping in mind practical RA clinical care.
24752345 Responsiveness of the EuroQol EQ-5D and Hospital Anxiety and Depression Scale (HADS) in rh 2014 Aug The aim of this study was to assess the responsiveness to change of the quality of life evaluated by the EuroQol Five Dimensions Questionnaire (EQ-5D) and Hospital Anxiety and Depression Scale (HADS) after biological treatment in a population of rheumatoid arthritis patients. A cohort of patients with RA (n = 29) treated with tocilizumab (TCZ) were analyzed in the study. The inclusion criteria were patients aged between 18 and 65 years, fulfilling American College of Rheumatology 1987 criteria for RA. All patients had inadequate response to methotrexate and with no prior biologic exposure. They were evaluated clinically including Disease Activity Score 28 (DAS28), and the European Quality of Life 5 Dimensions (EQ-5D) to measure the quality of life, and HAD assessed the anxiety and depression status at the initiation of treatment with anti-IL 6 receptor antibody agent and after 6 months. Sensitivity to change was quantified by the effect size (ES) before and after the treatment with TCZ. Among 29 patients with RA included in the study, 25 were females and 4 males. The mean age was 42 years ± 13.4 (SD). Three patients were excluded from the study before 24 weeks because of serious side effects, and five have missing data. The study population exhibited significant decreases in all measures of disease activity at 24 weeks. Physical activity expressed by the Health Assessment Questionnaire (HAQ) score increased through the observation period (for all p < 0.001). Sensitivity to change was high for the VAS and EQ-5D (ES 1.58 and 1.36, respectively) but only moderate for the HAD anxiety component (ES = 0.70) and small for the HAD depression component (ES = 0.4). The EQ-5D and VAS were more responsive than HADS to evaluate the quality of life on patient with RA treated with TCZ.
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.
23393145 Defining erosive disease typical of RA in the light of the ACR/EULAR 2010 criteria for rhe 2013 Apr BACKGROUND: According to the 2010 criteria, rheumatoid arthritis (RA) can be classified in the presence of ≥6 points on the criteria or 'typical' erosive disease. RA-specific erosiveness however has not been defined yet. This study reports the results of the data driven phase of a European League Against Rheumatism (EULAR) taskforce aiming to define RA-specific erosiveness. METHODS: Baseline radiographs of hands and feet of 980 Dutch and 811 French early arthritis patients were studied on the number and site of erosive joints. Test characteristics were determined, with the outcome measures being initiation of methotrexate (MTX) therapy or any disease modifying antirheumatic drug (DMARD) therapy within the first year of disease and arthritis persistency over 5 years. Analyses were repeated in the patients with <6 points on the American College of Rheumatology/EULAR 2010 criteria. RESULTS: In both cohorts comparable test characteristics were observed for the outcomes MTX therapy, any DMARD therapy and arthritis persistency. Test characteristics were not influenced by the site of erosiveness. The specificity observed was >50% for ≥1 erosive joint, >80% for ≥3 erosive joints and >90% for ≥5 erosive joints. When analysing the patients not fulfilling the 2010 criteria (n=308 and 149), specificity was >60% for ≥1 erosive joint, >90% for ≥3 erosive joints and >95% for ≥5 erosive joints. Few of these patients fulfilled the radiological criterion; 27-36 patients had ≥3 erosive joints and 13-14 patients had ≥5 erosive joints. CONCLUSIONS: RA-specific erosiveness can be defined with high specificity at several cut-offs for the number of erosive joints in two independent cohorts with multiple different outcomes. The final radiological criterion will be established in the next phase.
23565635 Will antirheumatic treatment improve cardiovascular outcomes in patients with rheumatoid a 2014 In recent years, the scientific community has gained significant insight into the complex interaction between inflammation and the cardiovascular system in patients with rheumatoid arthritis (RA), which leads to increased cardiovascular (CV) morbidity and mortality in these patients. Our common understanding of this association is that persistent inflammation contributes to the development of premature atherosclerosis. Consequently, the question arises whether control of inflammation with antirheumatic treatment will be able to improve CV outcome. While there are a lot of data that demonstrate improvement of numerous CV surrogate markers in patients treated with virtually all antirheumatic drug classes, there is much less information about the possible translation of these beneficial effects into improved CV outcome. In summary, the published evidence suggests that tumor necrosis factor (TNF) alpha inhibitors may improve CV outcome. The same is true for methotrexate (MTX). However, it is not clear whether MTX works via suppression of inflammation or through drug specific mechanisms. For other traditional disease-modifying antirheumatic drugs and biologic therapies, there are no convincing data for improved CV outcome. Only a few drugs (glucocorticoids and NSAIDs) have been associated with increased CV risk. Treating RA aggressively, as recommended by current guidelines, is likely to have a beneficial effect on CV outcomes.
25249397 CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator o 2014 Sep 24 INTRODUCTION: A key phenomenon in rheumatoid arthritis is the formation of lymphoid follicles in the inflamed synovial membrane. C-X-C motif chemokine 13 (CXCL13) is central in this process as it attracts C-X-C chemokine receptor type 5 (CXCR5)-expressing B cells and T follicular helper cells to the follicle. We here examine the role of CXCL13 and its association with disease in patients with treatment-naïve early rheumatoid arthritis. METHODS: Plasma samples from patients in the OPERA trial were examined for CXCL13 at treatment initiation and after 6 months of treatment with either methotrexate plus placebo (DMARD) (n = 37) or methotrexate plus adalimumab (DMARD + ADA) (n = 39). Treatment outcome was evaluated after 1 and 2 years. CXCL13 plasma levels in healthy volunteers (n = 38) were also examined. RESULTS: Baseline CXCL13 plasma levels were increased in early rheumatoid arthritis patients in comparison with healthy volunteers. Also, plasma CXCL13 correlated positively with disease activity parameters; swollen joint count 28 (rho = 0.34) and 40 (rho = 0.39), visual analog score (rho = 0.38) and simplified disease activity index (rho = 0.25) (all P <0.05). CXCL13 levels decreased a significantly twofold more in the DMARD + ADA group than in the DMARD group. Baseline CXCL13 plasma levels in the DMARD group correlated inversely with disease activity parameters; disease activity score in 28 joints, four variables, C-reactive protein based (DAS28CRP) (rho = 0.58, P < 0.05) at 12 months. High baseline CXCL13 was associated with remission (DAS28CRP less than 2.6) after 2 years. CONCLUSIONS: In treatment-naïve early rheumatoid arthritis patients, plasma CXCL13 levels were associated with joint inflammation. Furthermore, patients with high baseline plasma CXCL13 levels had an improved chance of remission after 2 years. We propose that high CXCL13 concentrations indicate recent onset of inflammation that may respond better to early aggressive treatment. Thus, high levels of CXCL13 could reflect the 'the window of opportunity' for optimal treatment effect. TRIAL REGISTRATION: Clinicaltrial.gov NCT00660647. Registered 10 April 2008.
24623617 Proof-of-concept study of a Web-based methotrexate decision aid for patients with rheumato 2014 Oct OBJECTIVE: To assess the extent to which an online patient decision aid reduced decisional conflict and improved self-management knowledge/skills in patients who were considering methotrexate for rheumatoid arthritis (RA). METHODS: We used a mixed-methods pre-post study design. Eligible participants had a diagnosis of RA, had been prescribed methotrexate but were unsure about starting it, and had access to the internet. Outcome included the Decisional Conflict Scale, the Methotrexate in RA Knowledge Test, and the Effective Consumer Scale. Paired t-tests were used to assess changes before and after the intervention. Randomly selected participants were interviewed at the end of the study about their experiences with the decision aid. RESULTS: Of 30 participants, 23 were women. Mean ± SD age was 54.9 ± 14.9 years and the median disease duration was 1 year (interquartile range 0.3-5.0 years). Mean ± SD decisional conflict changed from 49.50 ± 23.17 preintervention to 21.83 ± 24.12 postintervention (change -27.67 [95% confidence interval -39.89, -15.44]; P < 0.001). Knowledge of methotrexate improved (mean ± SD 30.62 ± 9.26 preintervention and 41.67 ± 6.81 postintervention; P < 0.001), but there was no change in effective consumer attributes (mean ± SD 68.24 ± 12.46 preintervention and 72.94 ± 12.74 postintervention; P = 0.15). Three themes emerged from interviews of 11 participants: seeking confirmation of one's own knowledge of methotrexate, amplifying reluctance when they encountered information contradicting their own experiences, and clarifying thoughts about the next step during the process. CONCLUSION: Patients' decisional conflict and knowledge improved after using the patient decision aid. Interview findings further highlighted the power of patients' prior knowledge and experiences with RA on how they approach the information presented in a decision aid.
23818718 Clinical, functional, and radiographic benefits of longterm adalimumab plus methotrexate: 2013 Sep OBJECTIVE: To examine the longterm effectiveness and safety of adalimumab in patients with longstanding rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX), and to assess the effect of a 1-year delay in initiation of combination therapy. METHODS: DE019 was a 1-year randomized controlled trial (RCT) in which patients received adalimumab 20 mg weekly, adalimumab 40 mg every other week (eow), or placebo; all received concomitant MTX. Patients completing the RCT could receive open-label adalimumab 40 mg eow + MTX for an additional 9 years. Clinical, functional, and radiographic outcomes were assessed using composite measures of disease activity (e.g., American College of Rheumatology responses, 28-joint Disease Activity Score with C-reactive protein, Simplified Disease Activity Index), Health Assessment Questionnaire-Disability Index, and the modified total Sharp score (mTSS), respectively. RESULTS: Of the 619 patients randomized, 457 entered the open-label extension; 202 completed 10 years. At Year 10, patients demonstrated effective disease control and inhibition of radiographic progression. Differences in clinical and functional responses between adalimumab + MTX and placebo + MTX observed during the RCT became less apparent at Year 10. Still, patients who initially received adalimumab + MTX had significantly lower mean ΔmTSS at Year 10 compared with patients who initially received placebo + MTX. No new safety signals arose following up to 10 years of adalimumab + MTX exposure. CONCLUSION: During up to 10 years of treatment with adalimumab + MTX, patients with longstanding RA experienced effective disease control with no change to the expected safety profile. A 1-year delay in receipt of adalimumab + MTX was associated with reduced effectiveness, suggesting that a window of opportunity to prevent irreversible damage exists even in a population with established RA.
24011160 [Clinical value of serum matrix metalloproteinase-3 in evaluating joint destruction and th 2013 Sep OBJECTIVE: To assess the clinical value of serum matrix metalloproteinase-3 (MMP-3) in evaluating joint destruction and therapeutic effect in rheumatoid arthritis (RA) patients. METHODS: The study included 109 RA patients and 23 healthy volunteers. Serum MMP3, C-reactive protein (CRP), rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody levels were detected. All relevant clinical information of RA patients were recorded. RESULTS: Serum RF, anti-CCP antibodies and MMP3 concentrations in RA patients were markedly higher than those in healthy controls, and serum anti-CCP antibodies and MMP3 levels significantly increased in active RA as compared with those in stable RA (P<0.05). Serum CRP, anti-CCP antibodies and MMP3 levels gradually rose with the progress of joint destruction, but only the increase of serum MMP3 was significant statistically (P<0.05). Serum MMP3 level was found positively correlated with serum CRP or RF levels or joint injury. After the combination treatment of TNF antagonist and methotrexate, DAS28 score, serum CRP, anti-CCP antibodies and MMP3 levels were markedly reduced (P<0.05), and the decrease of MMP3 level was the most obvious. CONCLUSION: Serum MMP3 was a good laboratory index to evaluate the joint injury status and therapeutic effect, which is superior to other traditional and routine laboratory indexes.
24766460 Targeting IL-6 for the treatment of rheumatoid arthritis: Phase II investigational drugs. 2014 Jul INTRODUCTION: IL-6 is a key cytokine in the pathogenesis of rheumatoid arthritis (RA). The clinical efficacy of tocilizumab (TCZ), a humanized anti-IL6-receptor mAb, confirmed the value of IL-6 blockade in this disease. A number of new anti-IL-6 biologics are currently in Phase I - III of clinical development for RA. AREAS COVERED: This article reviews the available results from Phase II trials of investigational anti-IL-6 agents in RA. The authors discuss the potential relevance of alternative IL-6-blocking agents, with regard to their specific molecular targets in IL-6 signaling pathways and to the main open questions in the clinical research agenda for anti-IL-6 biologics. EXPERT OPINION: The results of Phase II trials of new anti-IL-6 biologics show promising results in terms of efficacy. The most frequently reported adverse events were not unexpected based on previous experience with TCZ. Further evidence is needed to appraise whether the difference in molecular structure or in the specific target of new anti-IL-6 biologics might result in added therapeutic value over TCZ. New data from Phase III trials that provides a head-to-head comparison against TCZ and anti-TNF agents with or without methotrexate background treatment are expected in the future.
25381560 Coronary Artery Disease Evaluation in Rheumatoid Arthritis (CADERA): study protocol for a 2014 Nov 8 BACKGROUND: The incidence of cardiovascular disease (CVD) in rheumatoid arthritis (RA) is increased compared to the general population. Immune dysregulation and systemic inflammation are thought to be associated with this increased risk. Early diagnosis with immediate treatment and tight control of RA forms a central treatment paradigm. It remains unclear, however, whether using tumor necrosis factor inhibitors (TNFi) to achieve remission confer additional beneficial effects over standard therapy, especially on the development of CVD. METHODS/DESIGN: Coronary Artery Disease Evaluation in Rheumatoid Arthritis (CADERA) is a prospective cardiovascular imaging study that bolts onto an existing single-centre, randomized controlled trial, VEDERA (Very Early versus Delayed Etanercept in Rheumatoid Arthritis). VEDERA will recruit 120 patients with early, treatment-naïve RA, randomized to TNFi therapy etanercept (ETN) combined with methotrexate (MTX), or therapy with MTX with or without additional synthetic disease modifying anti-rheumatic drugs with escalation to ETN following a 'treat-to-target' regimen. VEDERA patients will be recruited into CADERA and undergo cardiac magnetic resonance (CMR) assessment with; cine imaging, rest/stress adenosine perfusion, tissue-tagging, aortic distensibility, T1 mapping and late gadolinium imaging. Primary objectives are to detect the prevalence and change of cardiovascular abnormalities by CMR between TNFi and standard therapy over a 12-month period. All patients will enter an inflammatory arthritis registry for long-term follow-up. DISCUSSION: CADERA is a multi-parametric study describing cardiovascular abnormalities in early, treatment-naïve RA patients, with assessment of changes at one year between early biological therapy and conventional therapy. TRIALS REGISTRATION: This trial was registered with Current Controlled Trials (registration number: ISRCTN50167738) on 8 November 2013.
25351212 Therapeutic effects of micheliolide on a murine model of rheumatoid arthritis. 2015 Jan Rheumatoid arthritis (RA) is a systemic autoimmune disease and collagen-induced arthritis (CIA) is an animal model for RA. Micheliolide (MCL) is a novel compound with strong anti-inflammatory effects. The present study was conducted to evaluate the therapeutic effects of MCL on RA. Mice were randomly divided into four groups and the CIA model mice were treated with methotrexate (MTX), MCL and dimethyl sulfoxide. A score associated with the severity of arthritis was assigned on alternate days from the 22nd day for 60 days. Histopathological changes and the serum levels of cytokines were measured on day 85. The results demonstrated that the MCL treatment group had arthritis scores lower than the CIA group and higher than the MTX group; compared with the CIA group, MCL and MTX significantly reduced the swelling of the paws and suppressed the degeneration of articular cartilage. Expression levels of macrophage colony-stimulating factor (M-CSF), tissue inhibitors of metalloproteinases-1 (TIMP-1) and complement component 5a (C5/C5a) were lower in the mice with arthritis compared with normal mice, however, following treatment with MCL and MTX, all the mice exhibited significant recovery to differing degrees. Unlike the MTX group, the MCL group failed to recover the level of soluble intercellular adhesion molecule-1. In addition, the cytokine of B-lymphocyte chemoattractant (BLC) solely presented in the MCL group. These results suggest that MCL may be considered for use as a novel therapeutic treatment against RA and that changes in the expression of cytokines C5/C5a, TIMP-1, M-CSF and BLC may underlie the mechanism by which MCL effects changes in this disease.
23554429 Levels of serum anti-Müllerian hormone, a marker for ovarian reserve, in women with rheum 2013 Sep OBJECTIVE: Fertility is reduced in women with rheumatoid arthritis (RA), even before diagnosis. This may be due to a diminished ovarian reserve. The current study examined serum levels of anti-Müllerian hormone (AMH), the most reliable endocrine marker for ovarian reserve, in early RA patients and the influence of disease activity and methotrexate (MTX) use on AMH concentrations. METHODS: Serum AMH levels were measured in 72 women with recent-onset RA ages 18-42 years and compared to 509 healthy women. The association between AMH and rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), erosions, C-reactive protein (CRP) level, disease activity (Disease Activity Score in 28 joints [DAS28]), and use of MTX was assessed. RESULTS: At diagnosis, age-adjusted serum AMH levels did not differ significantly between patients and controls (P = 0.254). AMH levels were not related to the presence of RF (P = 0.487), anti-CCP (P = 0.686), or erosions (P = 0.350), and showed no significant correlation with CRP levels (r = -0.207, P = 0.083) or disease activity scores (DAS28; r = 0.007, P = 0.955). After 6 months of treatment, AMH levels in patients (n = 53) were lower than at the time of diagnosis (P < 0.001), but did not differ from controls (P = 0.741). There was no significant difference in AMH values after 6 months of treatment between patients who did (n = 31) or did not (n = 22) receive MTX (P = 0.287). CONCLUSION: AMH levels in women with early RA are comparable to those of healthy controls, indicating that the reduced fertility in this patient group is not caused by diminished ovarian reserve. AMH levels are not affected either by disease activity or by short-term MTX use.
22532636 Impact of tumour necrosis factor inhibitor treatment on radiographic progression in rheuma 2013 Jan OBJECTIVES: To compare radiographic progression during treatment with disease-modifying antirheumatic drugs (DMARD) and subsequent treatment with tumour necrosis factor α inhibitors (TNF-I) in rheumatoid arthritis (RA) patients in clinical practice. METHODS: Conventional radiographs (x-rays) of hands and wrists were obtained ∼2 years before start (prebaseline), at baseline and ∼2 years after start (follow-up) of TNF-I. Clinical data were obtained from the DANBIO registry and the patient files. x-Rays were scored blinded to chronology according to the Sharp/van der Heijde method. Annual radiographic progression rates during the DMARD (prebaseline to baseline x-ray) and TNF-I (baseline to follow-up x-ray) periods were calculated. RESULTS: 517 RA patients (76% women, 80% IgM rheumatoid factor positive, 65% anticyclic citrullinated peptide positive, 40% current smokers, age 54 years (range 21-86), median disease duration 5 years (range 0-57)) were included. Patients were treated with infliximab (61%), etanercept (15%) or adalimumab (24%). During the DMARD period 85% of patients received methotrexate, 51% sulphasalazine and 78% prednisolone. The median DMARD period was 733 days (IQR 484-1002) and the median TNF-I period was 562 days (IQR 405-766). The median radiographic progression rate decreased from 0.7 (IQR 0-2.9) total Sharp score units/year (dTSS) in the DMARD period to 0 (0-0.9) units/year in the TNF-I period (p<0.0001, Wilcoxon). Corresponding mean dTSS values were 2.1 (SD 3.7) versus 0.7 (SD 2.3) units/year (p<0.0001, paired t test). 305 patients progressed (dTSS >0) in the DMARD period compared with 158 patients in the TNF-I period (p<0.0001, χ(2)). CONCLUSION: This nationwide observational study of RA patients documented significantly reduced radiographic progression during TNF-I treatment compared with the previous period of DMARD treatment.
25244345 An update on disease modifying antirheumatic drugs. 2014 Disease modifying antirheumatic drugs (DMARDs) is a category of drugs which is used as medication in various arthritic conditions to arrest the progression of disease along with relief from pain. About 83% of population worldwide uses DMARDs. Withdrawal of COX-2 inhibitors because of cardiovascular side effects and short-term action associated with glucocorticoids provided a motivation for development of newer DMARDs. Currently non- biological DMARDs like methotrexate, sulfasalazine, hydroxychloroquine and azathioprine serve the purpose of relieving pain and inhibiting the progression of disease. Biological DMARDs like toclizumab, adalimumab, infliximab, golimumab and abatacept have shown more efficacy and lesser side effects as compared to non- biological DMARDs but their access to patient is less because of higher cost. DMARDs act by different mechanisms against inflammation like inhibition of tumor necrosis factor, suppression of IL-1 and TNF-α, induction of apoptosis of inflammatory cells, by increasing chemotactic factors, inhibition of purine synthesis, pyrimidine metabolism or purine embolism. DMARDs have important applications in diseases like rheumatoid arthritis, Crohn's disease, juvenile idiopathic arthritis, psoriatic arthritis and myasthenia gravis. Present review mainly focuses on DMARDs and their clinical applications giving an overview of their mechanism of action, pharmacokinetic properties, advantages over conventional therapies, shortcomings and recent trends.
23950188 Disease factors in early rheumatoid arthritis are associated with differential risks for c 2013 Dec OBJECTIVE: To investigate, within the first 2 years of diagnosis with rheumatoid arthritis (RA), associations between disease-related measures and cardiovascular disease (CVD) and mortality in patients with RA onset before and after 65 years of age. METHODS: The study population (n = 741; 67.5% women) was derived from the Better Anti-Rheumatic Pharmaco Therapy (BARFOT) early RA cohort, recruited 1993-1999. The mean age was 55 years (SD 14.7). The outcomes were incident CVD events and all-cause mortality until 2010. Area under the curve (AUC) for disease measures at inclusion, 1 and 2 years, and decrease in measures after 1 year were calculated. RESULTS: In all, 177 CVD events and 151 deaths occurred over 10 years of observation. In adjusted Cox regression analyses, seropositivity for rheumatoid factor (RF) or anticitrullinated protein antibodies (ACPA); white blood (cell) count at diagnosis; and AUC of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and visual analog scale (VAS)-pain were associated with higher CVD risk among patients with disease onset before 65 years of age. Among patients with disease onset after 65 years, larger decreases in CRP, ESR, health assessment questionnaire (HAQ), and use of methotrexate decreased CVD risk, whereas use of glucocorticoids heightened CVD risk. AUC of CRP, ESR, HAQ, and HAQ after 2 years was related to risk of death in both age groups. Seropositivity and AUC for VAS-pain in the younger group and use of glucocorticoids in the elderly were associated with poorer survival. CONCLUSION: Early treatment of RA may improve longterm outcomes. Presence of RF or ACPA associates with CVD and mortality among RA patients with disease onset before 65 years. Age stratification may improve evaluation of risk for CVD and mortality in early RA.