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ID PMID Title PublicationDate abstract
21803751 Rheumatoid arthritis near remission: clinical rather than laboratory inflammation is assoc 2011 Nov BACKGROUND: Disease activity in rheumatoid arthritis (RA) can be measured clinically (eg, swollen joint count (SJC)) or systemically (eg, C reactive protein (CRP)). In general, both contribute to the progression of joint damage, but the relevance of residual inflammation in patients near remission is unclear. OBJECTIVE: To determine the independent contribution of SJC and CRP to progression of joint damage in patients near remission. METHODS: Data from methotrexate monotherapy arms of the ASPIRE, ERA, Leflunomide, PREMIER and TEMPO trials (n=1184) were pooled and the average SJC and CRP values from visits at 6, 9 and 12 months were determined. The two variables were then dichotomised into active and inactive, where inactive was defined as a mean. Radiographic outcomes were assessed according to these definitions. RESULTS: The greatest progression was seen in patients in whom both SJC and CRP were active and the smallest in those in whom both were inactive. If SJC was inactive, radiographic progression was not different between those with inactive or active CRP (0.7 ± 4.3/year and 0.8 ± 5.4/year, respectively, p=0.19). However, if CRP was inactive (<1 mg/dl), SJC status still determined radiographic progression (0.7 ± 4.3/year and 1.8 ± 5.6/year, for inactive and active SJC, respectively, p=0.004). The importance of SJC in patients with inactive CRP was also shown in a linear model (p=0.019), while CRP was not significantly different in patients with inactive SJC (p=0.40). CONCLUSION: In patients with RA who are near remission, the amount of joint swelling appears to be more predictive of radiographic progression than the amount of CRP.
21128990 Eternacept for the treatment of patients with rheumatoid arthritis and concurrent intersti 2012 Feb WHAT IS KNOWN AND OBJECTIVE: Tumour necrosis factor-α (TNF-α)-blocking agents are increasingly used in the management of refractory rheumatoid arthritis (RA). Although effective, they are associated with rare but potentially fatal adverse effects, including interstitial lung disease (ILD). In patients with pre-existing ILD, eternacept (ETN) monotherapy is often regarded as a suitable choice. Other anti-TNF-α blockers such as infliximab and adalimumab, are used in combination therapy with methotrexate (MTX) in most of the cases. We report on a case of fatal exacerbation of ILD in a patient given ETN monotherapy and review the literature on ETN-associated ILD. METHODS: We report on a case of a 75-year-old male with RA who developed severe ILD after the introduction of ETN, and we undertook a literature search to identify other reports of similar cases. We then critically assessed those reports. RESULTS AND DISCUSSION: In addition to our case, 11 other patients have been reported to have developed ILD in association with the use of ETN. Six patients had pre-existing ILD. Although four patients received MTX, eight patients developed severe ILD without MTX. Ten patients recovered after termination of ETN, although two patients died. WHAT IS NEW AND CONCLUSION: Although ETN is often regarded as safe for patients with ILD, our case and the literature reports suggest that caution is still required.
22505694 Incidence of new-onset and flare of preexisting psoriasis during rituximab therapy for rhe 2012 May OBJECTIVE: Psoriasis could be a paradoxical reaction to tumor necrosis factor-α antagonist therapy and it has been reported with rituximab therapy. Our objective was to assess the rates of new-onset and flare of preexisting psoriasis in patients taking rituximab for rheumatoid arthritis (RA). METHODS: The nationwide multicenter prospective AutoImmunity and Rituximab (AIR) registry was set up in 2006 by the French Society for Rheumatology to collect data on patients taking rituximab for joint diseases. We identified patients with RA in the registry who had psoriasis listed as an adverse drug reaction, and we obtained additional information from their physicians if needed. We computed the incidence rates of new-onset and flare of preexisting psoriasis according to the rituximab exposure time. RESULTS: Among the 1927 patients in the registry with RA, 2 had new-onset and 5 had flare of preexisting psoriasis after a median followup of 39.2 weeks. Incidence rates were 1.04/1000 person-years (95% CI 0.13 to 3.8) for new-onset psoriasis and 2.6/1000 person-years (95% CI 0.84 to 6.1) for flare of preexisting psoriasis. Rituximab rechallenge in the 2 new-onset cases and in 2 flare cases was not followed by recurrence or exacerbation of psoriasis. Two of the 5 flare cases developed after discontinuation of methotrexate. CONCLUSION: Despite the small number of cases observed, leading to wide CI, the incidence rates in our study do not support a causative role of rituximab therapy in new-onset or flare of preexisting psoriasis in patients with RA.
22284820 Local administration of glucocorticoids decreases synovial citrullination in rheumatoid ar 2012 Jan 27 INTRODUCTION: Protein citrullination is present in the rheumatoid synovium, presumably contributing to the perpetuation of chronic inflammation, in the presence of specific autoimmunity. As a result, the present study examined the possibility that effective antirheumatic treatment will decrease the level of synovial citrullination. METHODS: Synovial biopsies were obtained from 11 rheumatoid arthritis (RA) patients before and after 8 weeks of treatment with 20 mg methotrexate weekly, 15 RA patients before and 2 weeks after an intraarticular glucocorticoid injection, and eight healthy volunteers. Synovial inflammation was assessed with double-blind semiquantitative analysis of lining thickness, cell infiltration, and vascularity by using a 4-point scale. Expression of citrullinated proteins (CPs) with the monoclonal antibody F95 and peptidylarginine deiminase (PAD) 2 and 4 was assessed immunohistochemically with double-blind semiquantitative analysis. In vitro synovial fluid (SF), peripheral blood (PB), mononuclear cells (MCs), and synovial explants obtained from RA patients were incubated with dexamethasone and analyzed with immunohistochemistry for expression of CP as well as PAD2 and PAD4 enzymes. RESULTS: The presence of synovial CP was almost exclusive in RA compared with healthy synovium and correlated with the degree of local inflammation. Treatment with glucocorticoids but not methotrexate alters expression of synovial CP and PAD enzymes, in parallel with a decrease of synovial inflammation. Ex vivo and in vitro studies suggest also a direct effect of glucocorticoids on citrullination, as demonstrated by the decrease in the level of citrullination and PAD expression after incubation of SFMC and synovial explants with dexamethasone. CONCLUSION: Synovial citrullination and PAD expression are dependent on local inflammation and targeted by glucocorticoids.
22402142 Combination etanercept and methotrexate provides better disease control in very early (<=4 2012 Jun OBJECTIVE: The objective of this post hoc analysis was to test the benefits of treating very early rheumatoid arthritis (VERA; ≤4 months) using COMET trial data. Treatment response in VERA and early rheumatoid arthritis (ERA; >4 months to 2 years) with combination etanercept+methotrexate (ETN+MTX) or MTX monotherapy was compared. METHODS: Data assessed at week 52 for baseline disease duration effect included remission (disease activity score (DAS)28 <2.6, SDAI ≤3.3, Boolean), low disease activity (LDA; DAS28 <3.2), Boolean components of remission and radiographic non-progression. Subjects who discontinued because of lack of efficacy were included as non-responders. RESULTS: Higher proportions of VERA subjects achieved LDA (79%) and DAS28 remission (70%) than ERA (62%, 48%, respectively, p<0.05) with ETN+MTX. Such high responses with MTX monotherapy were not observed (VERA, LDA=47%, DAS28 remission=35%; ERA, 47% and 32% respectively, p>0.70 for each). Regardless of disease duration, no radiographic progression was seen in 80% of subjects with ETN+MTX. In contrast, a higher proportion of VERA subjects showed no radiographic progression compared with ERA subjects treated with MTX (73.9% vs 50%, p=0.01). CONCLUSIONS: Treatment of VERA with ETN+MTX provides qualitatively improved clinical outcomes not seen with MTX monotherapy, supporting the pivotal role of TNF inhibition in early disease.
21751641 Post-chikungunya chronic arthritis--our experience with DMARDs over two year follow up. 2011 Feb AIM: 1) To study clinical features and laboratory findings in patients of post chikungunya chronic arthritis (PCCA). 2) To study effectivity of disease modifying antirheumatic drugs (DMARDs) in treatment of post-chikungunya chronic arthritis. MATERIALS AND METHODS: Sixteen Chikungunya IgM positive patients having arthritis lasting more than 3 months in spite of NSAIDs and Hydroxychloroquine therapy were selected. Their clinical, laboratory and radiological features were noted. Disease activity was assessed by clinical parameters and Disease Activity Score System (DAS 28). Functional status was assessed by HAQ Questionnaire on follow-up visits over next 2 years. Effectivity of treatment with Sulfasalazine and Methotrexate was assessed. RESULTS: Chronic inflammatory polyarthritis does occur following chikungunya infection. It involves large and small joints of hands and feet and is erosive and deforming. It is rheumatoid factor negative. AntiCCP antibody was positive in majority. Synovial biopsy revealed nongranulomatous chronic synovitis with infiltration with lymphocytes and plasma cells. It was negative for chikungunya RNA. Treatment with Sulfasalazine with and without methotrexate produced good response in 71.4 % and 12.5% respectively. CONCLUSIONS: Chronic inflammatory, erosive and rarely deforming polyarthritis does occur after acute chikungunya infection in some (5.6%). It is seronegative and AntiCCP positive in majority. DMARDs like sulfasalazine and methotrexate are required and effective in treatment of PCCA.
21240618 In rheumatoid arthritis patients treated with tocilizumab, the rate of clinical disease ac 2011 Aug We aimed to evaluate the efficacy of tocilizumab in patients with rheumatoid arthritis (RA), using the clinical disease activity index (CDAI), and to determine the baseline variables associated with CDAI remission. Fifty-eight patients with active RA were enrolled. We tried to evaluate whether baseline variables were associated with CDAI remission at 24 weeks. Twenty-two of the 58 patients (37.9%) had received tumor necrosis factor (TNF) inhibitors. The continuation rate of tocilizumab at 24 weeks was 87.9%. The seropositivity rates of IgM-rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies at baseline were both 91.4%. The rate of CDAI remission at 24 weeks was 20.7%. We selected baseline variables including age, gender, duration of disease, concomitant use of glucocorticoids, concomitant use of methotrexate (MTX), previous anti-TNF therapy, titer of anti-CCP antibodies (high or low toward median), titer of IgM-RF (high or low toward median), and CDAI, and found that a high titer of IgM-RF was the only variable to be associated with CDAI remission, according to univariate and logistic regression analyses. This is a new finding, and may be specific to tocilizumab as compared with previous observations in anti-TNF therapy.
21711059 Role of spleen tyrosine kinase inhibitors in the management of rheumatoid arthritis. 2011 Jun 18 Spleen tyrosine kinase (Syk) is a cytoplasmic tyrosine kinase involved in signalling in many of the cells that drive immune inflammation. The development of small molecules that inhibit Syk kinase may change the way we treat disorders such as rheumatoid arthritis (RA), as well as a range of other inflammatory diseases. Fostamatinib (R-788) is an orally bioavailable small molecule. It is the prodrug of R406, which is a potent Syk inhibitor. Fostamatinib was developed because it has more favourable physiochemical properties. It is rapidly converted to R406 by intestinal enterocytes. It has been evaluated in experimental models of RA, such as collagen-induced arthritis. In these models, fostamatinib suppressed clinical arthritis, bone erosions, pannus formation and synovitis. A phase II programme with fostamatinib has largely been completed. Three key trials have been published, lasting 12-26 weeks and each enrolling 189-457 patients (875 in total). All these trials involved placebo therapy and patients continued to receive methotrexate in addition to active treatment with fostamatinib. The first dose-ranging trial evaluated three treatment doses in RA patients who had not fully responded to methotrexate therapy. The second trial compared two treatment doses in patients who had not responded to methotrexate therapy. The third trial compared a single treatment dose with placebo in patients who had not responded to biological therapy. The primary outcome measure was the number of patients achieving American College of Rheumatology (ACR) 20% (ACR20) responses. Placebo ACR20 response rates in all three trials were similar (35-38%). All three trials involved one treatment arm receiving fostamatinib 100 mg twice daily; ACR20 responses with this active treatment ranged from 38% to 67%. A meta-analysis of ACR responses in these trials, using responses to the highest dose in each trial for comparisons with placebo therapy in a random effects model, showed a borderline benefit with ACR20 responses. There were more significant differences with ACR50 and ACR70 responses. The reason that this meta-analysis was not more strongly positive is that the third trial, which evaluated patients who had failed to respond to biological treatments, gave negative results. Individual ACR response components, such as changes in swollen joint counts, showed significant differences in the first two trials, but there were no definite treatment benefits in the third trial. Overall, the differences were significant in a meta-analysis of all three trials. The most important adverse reactions were diarrhoea, neutropenia and raised ALT levels, which all showed significant excesses with active treatment compared with placebo. Too few patients have been studied for a definitive safety profile to be known. Overall, the results of the phase II trials were sufficiently encouraging for a phase III programme to be initiated. It will be some years before their definitive results are available.
21702090 Very early improvements in the wrist and hand assessed by power Doppler sonography predict 2011 Oct OBJECTIVE: To investigate the response of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) by ultrasonographic evaluation of changes in the wrist and hand, and to determine whether such assessments during early TCZ treatment predict later clinical outcome. METHODS: Thirty-two RA patients about to receive TCZ treatment were examined by ultrasound at baseline and after 2 weeks using the Outcome Measures in Rheumatology Clinical Trials semiquantitative scoring of 22 joints (both wrists, proximal interphalangeal joints 1-5, and metacarpophalangeal joints 1-5) as well as clinical and laboratory variables, leading to a calculation of composite indexes. The aim was to determine whether methotrexate treatment and clinical, laboratory, and ultrasonographic evaluation after 2 weeks of TCZ treatment predict treatment outcome at 24 weeks, as assessed by the Disease Activity Score in 28 joints (DAS28). RESULTS: Changes of ultrasound scores after 2 weeks were found to be correlated with changes in DAS28 at 24 weeks (r = 0.545-0.622, P < 0.05). The change of sum power Doppler scores after 2 weeks of treatment was identified as the variable most closely correlated with the change in DAS28 at 24 weeks (r = 0.622, P < 0.05). CONCLUSION: The best predictors after 2 weeks of favorable treatment outcome at 24 weeks were improved power Doppler scores. Methotrexate treatment and composite indexes did not predict favorable treatment outcome in this study.
21666989 Investigation of the association between metabolic syndrome and disease activity in rheuma 2011 Jun 9 Rheumatoid arthritis (RA) is the most common form of autoimmune arthritis. Increased prevalence of metabolic syndrome (MetS) in RA may occur secondary to specific drug treatment and reduced physical activity associated with this condition. However, some recent studies suggest contradictory theories about the association of RA with MetS. This study was designed to evaluate the frequency of MetS in RA patients and the relationship between MetS with RA disease activity and body mass index (BMI). The study was conducted on 120 RA patients and 431 age- and sex-matched apparently healthy controls. A considerable proportion of patients were being treated with prednisolone and/or methotrexate and/or hydroxychloroquine. Disease activity was measured by the 28 joint count of disease activity score-Cerythrocyte sedimentation rate (DAS28ESR). MetS was evaluated according to International Diabetic Federation (IDF) and Adult Treatment Panel III (ATP III) criteria. The prevalence of MetS was significantly higher in the control group (p = 0.005). We did not find any difference in the prevalence of MetS between the patients with DAS < 3.2 and DAS ≥ 3.2. There was no association between the DAS28 score and the presence of MetS components by either definition. Multiple logistic regression analysis showed that the odds of a DAS > 3.2 in patients with BMI between 25 and 30 kg/m2 (OR = 0.1, p = 0.01) and BMI > 30 kg/m2 (OR = 0.3, p = 0.1), in comparison to BMI < 25 kg/m2, was 1/5 and 1/3, respectively. RA was not found to increase the risk of MetS. In addition, disease activity in RA patients was not influenced by the presence of MetS.
21499916 Mastocytic enterocolitis as a rare cause of chronic diarrhea in a patient with rheumatoid 2011 May The prevalence of chronic diarrhea within the U.S. population has been reported to be as high as five per cent, and numerous causes have been identified. Especially in patients suffering from rheumatoid arthritis drug therapy should be considered as possible cause. We report a case of chronic diarrhea triggered by mastocytic enterocolitis in a patient suffering from rheumatoid arthritis. Systemic mastocytosis and other causes of chronic diarrhea, especially therapy with methotrexate, were carefully ruled out. Treatment with desloratadin and ranitidine was initiated and led to a rapid and persistent amelioration of clinical symptoms. The diagnosis of mastocytic enterocolitis should be considered in patients with chronic diarrhea and normal clinical, laboratory, as well as endoscopical work-up.
22915617 Association of joint space narrowing with impairment of physical function and work ability 2013 Jul OBJECTIVES: Tumour necrosis factor inhibition plus methotrexate is believed to inhibit radiographic progression independent of inflammation. This analysis assessed whether these protective effects are exerted on bone (joint erosion; JE) and/or cartilage (joint space narrowing; JSN), and what the independent effects of JE/JSN progression are on longer-term patient-reported outcomes. METHODS: PREMIER was a 2-year, randomised, controlled trial of adalimumab plus methotrexate (ADA+MTX) versus the monotherapies. The impact of treatment on the relationships between time-averaged disease activity (TA-DAS28(CRP)) and changes in JE/JSN and associations of JE/JSN with the disability index of the health assessment questionnaire (HAQ-DI) at baseline and weeks 52 and 104 were assessed through non-parametric approaches of analysis of variance and quantile regression. JE/JSN association with employment status was evaluated at baseline and weeks 52 and 104 through logistic regression. RESULTS: Increasing tertiles of TA-DAS28(CRP) were associated with JE and JSN progression in the monotherapy groups, a phenomenon largely absent in ADA+MTX-treated patients. Although JSN was not associated with HAQ-DI at baseline, it was at 52 and 104 weeks. In contrast, JE was not associated with HAQ-DI at any time point examined. Odds of being employed at baseline, 52 weeks and 104 weeks were significantly associated with lower JSN, but not JE, scores. CONCLUSIONS: ADA+MTX inhibited both JE and JSN progression independently of disease activity. JSN played a more prominent role in patient-reported outcomes than JE. Preventing the onset or worsening of JSN probably represents a critical aspect of effective disease management of early rheumatoid arthritis patients.
22629396 Clinical significance of cartilage biomarkers for monitoring structural joint damage in rh 2012 PURPOSE: With the current use of biologics in rheumatoid arthritis (RA), there is a need to monitor ongoing structural joint damage due to the dissociation of articular cartilage damage from disease activity of RA. This study longitudinally analyzed levels of serum cartilage biomarkers during 54 weeks of infliximab therapy, to evaluate the feasibility of biomarkers for monitoring structural joint damage. METHODS: Subjects comprised 33 patients with early RA and 33 patients with established RA. All patients received 3 mg/kg of infliximab and methotrexate for 54 weeks. Levels of the following serum cartilage markers were measured at baseline and at weeks 14, 22, and 54: hyaluronan (HA); cartilage oligometric matrix protein (COMP); type II collagen (CII)-related neoepitope (C2C); type II procollagen carboxy-propeptide (CPII); and keratin sulfate (KS). Time courses for each biomarker were assessed, and relationships between these biomarkers and clinical or radiographic parameters generally used for RA were investigated. RESULTS: Levels of CRP, MMP-3, DAS28-CRP, and annual progression of TSS were improved to similar degrees in both groups at week 54. HA and C2C/CPII were significantly decreased compared to baseline in the early RA group (p<0.001), whereas HA and COMP, but not C2C/CPII, were decreased in the established RA group. Strikingly, serum C2C/CPII levels were universally improved in early RA, regardless of EULAR response grade. Both ΔHA and ΔC2C/CPII from baseline to week 54 correlated significantly with not only ΔCRP, but also ΔDAS28 in early RA. Interestingly, when partial correlation coefficients were calculated by standardizing CRP levels, the significant correlation of ΔHA to ΔDAS28 disappeared, whereas correlations of ΔC2C/CPII to ΔDAS28, ΔJNS, and ΔHAQ remained significant. These results suggest a role of ΔC2C/CPII as a marker of ongoing structural joint damage with the least association with CRP, and that irreversible cartilage damage in established RA limits restoration of the C2C/CPII level, even with tight control of joint inflammation. CONCLUSION: The temporal course of C2C/CPII level during anti-TNF therapy indicates that CII turnover shifts toward CII synthesis in early RA, but not in established RA, potentially due to irreversible cartilage damage. ΔC2C/CPII appears to offer a useful marker reflecting ongoing structural joint damage, dissociated from inflammatory indices such as CRP and MMP-3.
22139200 [The other opinion: nephrotoxicity of low-dose methotrexate - a problem which does not exi 2011 Dec The nephrotoxicity of methotrexate (MTX) is a phenomenon which is observed in high-dose therapy for treatment of malignant diseases. Even low-dose MTX therapy for treatment of rheumatic diseases is claimed to cause impairment in renal function. The necessity to adapt the dosage of MTX therapy for renal function disorders due to other causes however has first priority. The following article describes why nephrotoxicity of low-dose MTX has no clinical relevance and why in contrast non-steroidal anti-rheumatic drugs (NSARDs) are a problematic nephrotoxic group of substances and a long-term elimination from the therapeutic armamentarium for rheumatoid arthritis (RA) should be instigated.
21515916 Discontinuation of infliximab and potential predictors of persistent low disease activity 2011 Aug OBJECTIVE: To describe the disease course after the cessation of infliximab in early rheumatoid arthritis patients with disease activity score (DAS)-steered treatment and to identify predictors of persistent low disease activity. METHODS: In a post-hoc analysis of the BeSt study, disease activity and joint damage progression were observed in patients treated with methotrexate plus infliximab, who discontinued infliximab after achieving low disease activity (DAS ≤2.4) for 6 months. Predictors were identified using Cox regression analysis. RESULTS: 104 patients discontinued infliximab, of whom 77 had received infliximab plus methotrexate as initial treatment. Mean DAS at the time of infliximab cessation was 1.3, median symptom duration was 23 months and median Sharp/van derHeijde score was 5.5. The median follow-up was 7.2 years. Infliximab was re-introduced after loss of low disease activity in 48%, after a median of 17 months. The joint damage progression rate did not increase in the year after cessation, regardless of flare. After re-introduction of infliximab, 84% of these patients again achieved a DAS ≤2.4. In the multivariable model, smoking, infliximab treatment duration ≥18 months and shared epitope (SE) were independently associated with the re-introduction of infliximab: 6% of the non-smoking, SE-negative patients treated <18 months needed infliximab re-introduction. CONCLUSION: Cessation of infliximab was successful in 52%, with numerically higher success rates in patients initially treated with infliximab. Of the 48% who flared, 84% regained low disease activity. The joint damage progression rate did not increase in the year after cessation. Smoking, long infliximab treatment duration and SE were independently associated with re-introduction of infliximab.
22021897 Treating to target matrix metalloproteinase 3 normalisation together with disease activity 2012 Apr OBJECTIVES: To assess whether therapy to achieve both a disease activity score in 28 joints (DAS28) less than 2.6 and matrix metalloproteinase (MMP) 3 normalisation offers better outcomes than either target alone in early rheumatoid arthritis (RA) at 56 weeks: Treating to Twin Targets (T-4) Study. METHODS: 243 early RA patients were randomly allocated to one of four strategy groups: routine care (R group; n=62); DAS28-driven therapy (D group; n=60); MMP-3-driven therapy (M group; n=60); or both DAS28 and MMP-3-driven therapy group (twin; T group; n=61). Medication was started with sulfasalazine (1 g/day) in all intervention groups. Targets were DAS28 less than 2.6 for the D group, MMP-3 normalisation for the M group and both DAS28 less than 2.6 and MMP-3 normalisation for the T group. If the value in question did not fall below the previously measured level, medication was intensified, including methotrexate, other disease-modifying antirheumatic drugs and biological agents. Primary, secondary and outcome measures consisted of the proportions of patients showing clinical remission (DAS28 <2.6), radiographic non-progression (Δmodified total Sharp score ≤0.5), normal physical function (modified health assessment questionnaire score 0), or comprehensive disease remission defined as the combination of clinical remission, radiographic non-progression and normal physical function. RESULTS: Clinical remission at 56 weeks was achieved by more patients in the T group (56%) than in the R group (p<0.0005) or M group (p<0.0005). CONCLUSIONS: Results of the T-4 Study reveal that a twin target strategy can achieve a high clinical remission rate in early RA.
22273590 Up-regulated dipeptidyl-peptidase IV (CD26) on monocytes was unaffected by effective DMARD 2012 Jan OBJECTIVES: To study the CD26 density on monocytes and CD4+ T-lymphocytes in steroid and DMARD-naïve, early rheumatoid arthritis (RA) patients and to analyse for correlations with disease activity, including long-term radiographic progression. METHODS: Forty patients with active, early steroid and DMARD naïve RA (<6 months' duration) were randomised to treatment with methotrexate (MTX) versus MTX and cyclosporine A (CYA). Controls were 15 healthy age and gender matched subjects. Peripheral blood mononuclear cells were analysed for CD26 density by flow cytometry at baseline and after 52 weeks. Radiographic progression was scored by delta total Sharp-van der Heijde score (TSS) from 0 to 5 years. RESULTS: The density of CD26 on monocytes (CD3-CD14+) in RA was up-regulated compared to healthy controls (p<0.0001) and remained unaffected by clinically effective DMARD treatment after 52 weeks. In anti-CCP positive RA patients (n=18) baseline CD26 density on monocytes correlated to 5-year radiographic progression (p=0.008, r=0.60). The density of CD26 did not correlate to DAS28, the swollen or tender joint count or CRP-level at baseline or at year one. The CD26 density on CD4+ T-lymphocytes at week 0 was comparable to healthy controls (p=0.34). CONCLUSIONS: The up-regulated density of CD26 on monocytes in steroid and DMARD naïve active early RA was unaffected by 52 weeks of effective DMARD treatment and correlated to 5-year radiographic progression.
22426579 Limited end-user knowledge of methotrexate despite patient education: an assessment of rhe 2012 Apr BACKGROUND: Methotrexate (MTX) is a first-line disease-modifying agent and anchor drug for biologic therapy used in rheumatoid arthritis and other inflammatory rheumatic disorders. Adverse effects are a common cause of drug discontinuation and include preventable serious incidents that may result in patient harm or death. OBJECTIVES: The objective of this study was to audit adherence by health professionals to national and international guidelines for patient education and risk reduction in patients prescribed MTX for inflammatory rheumatic diseases. METHODS: A combination of interviews, case record reviews, and self-administered patient knowledge questionnaires with individual patient feedback was used. The setting was the rheumatology outpatient department of a district general hospital. RESULTS: Fifty-one patients participated in the audit. The mean age was 58.6 (SD, 13.1) years and median duration of disease was 3.7 years (interquartile range, 1.7-7.6 years). Nurse-led patient education was documented at baseline for 94.1% of participants. Despite this, only 11.8% of participants recognized the potentially lethal drug-drug interaction with trimethoprim/Septrin (co-trimoxazole), and less than 60.8% recognized possible major adverse effects related to MTX. Although lifestyle implications relating to alcohol consumption and pregnancy/breast-feeding were recognized by the majority, only 52.9% of males were aware of recommendations in relation to conception. Univariable and multivariable analyses identified male sex, not speaking English as a first language, and a longer duration of therapy as predictors of lower levels of patient knowledge. CONCLUSIONS: Despite consistent baseline patient education, end-user knowledge and awareness pertinent to MTX safety are limited. Good-quality written information in the most appropriate language, patient feedback on educational programs, follow-up testing of patient knowledge, and targeted reeducation are recommended to address individual deficiencies in core knowledge.
22646866 Effect of very early treatment in rheumatoid arthritis on bone oedema and synovitis, using 2012 Oct OBJECTIVE: To evaluate the magnetic resonance imaging (MRI) findings of hand involvement before and 1 year after treatment in patients with early rheumatoid arthritis (RA). METHOD: MRI of the dominant hand was performed in 22 patients fulfilling the new criteria for early RA. The patients were divided into three groups. Nine had very early RA (VERA; disease duration < 3 months), seven had early RA (ERA; disease duration < 6 months), and six had established RA (ESTRA; disease duration > 12 months). The MRI protocol consisted of fat-suppressed T2, and plain and contrast-enhanced T1-weighted sequences. Assessment of bone marrow oedema, synovitis, and bone erosions was performed by the OMERACT RA MRI scoring system. Patients were treated with methotrexate (MTX) 0.2 mg/kg/body weight/week and prednisone 7.5 mg/day. Clinical assessment was evaluated using the Disease Activity Score for 28 joint indices (DAS28). RESULTS: After treatment, a significant decrease was observed: (a) in DAS28 of VERA (6.2 ± 0.9 vs. 2.4 ± 1.2), ERA (5.3 ± 0.8 vs. 2.8 ± 1.0), and ESTRA patients (5.7 ± 8.0 vs. 2.7 ± 0.7; p < 0.05); (b) in bone oedema (16.77 ± 13.78 vs. 5.88 ± 6.31) and synovitis (12.44 ± 6.44 vs. 2.88 ± 3.25) of VERA patients; and (c) in synovitis (7.57 ± 6.32 vs. 1.42 ± 1.81) of ERA patients (p < 0.05). No significant difference was found in erosions in any group. CONCLUSION: Bone marrow oedema and synovitis decrease significantly when RA is diagnosed and treated early. MRI is useful in the early detection of these changes. MTX treatment resulted in a significant decrease in DAS28 score and significant improvement in bone oedema and synovitis.
21041278 Effect of atorvastatin on inflammation and modification of vascular risk factors in rheuma 2011 Feb OBJECTIVE: To investigate the effect of atorvastatin therapy on inflammation, disease activity, endothelial dysfunction, and arterial stiffness in patients with rheumatoid arthritis (RA). METHODS: This study included 30 patients with early RA, randomly divided into 2 groups. Group 1 (n = 15) received methotrexate (MTX; 0.2 mg/kg/week; mean (15.5 ± SD 1.3) plus prednisone (10 mg/day). Group 2 (n = 15) received MTX and prednisone with the same previous doses plus atorvastatin therapy (40 mg/day). Ten healthy individuals of similar age and sex served as controls. Disease activity, lipid profile, serum malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), resistin, adiponectin, and brachial artery flow-mediated dilation (FMD) were measured before and after 6 months of treatment. RESULTS: Atorvastatin combined with MTX therapy significantly reduced serum total cholesterol, low-density lipoprotein cholesterol, and triglycerides, and increased high-density lipoprotein cholesterol (p < 0.001). Disease activity variables, serum MDA, TNF-α, resistin, adiponectin, and FMD were significantly improved by the drug combinations (p < 0.001). CONCLUSION: Atorvastatin therapy in patients with RA reduced disease activity and conventional and novel vascular risk factors that promote the atheromatous lesion. Therapy was also associated with concomitant improvement in endothelial function.