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ID PMID Title PublicationDate abstract
19454108 Rheumatoid arthritis. 2007 Aug 1 INTRODUCTION: Rheumatoid arthritis usually starts as a symmetrical polyarthritis, and its course is marked by flares and remissions. The aims of treatment are to relieve pain and swelling, and to improve function. In addition, disease-modifying antirheumatic drugs (DMARDs) may reduce disease progression. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments in people with rheumatoid arthritis who have not previously received any disease-modifying antirheumatic drug treatment? How do different drug treatments compare in people with rheumatoid arthritis who have either not responded to or are intolerant of first-line disease-modifying antirheumatic drugs? We searched: Medline, Embase, The Cochrane Library and other important databases up to June 2005 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 62 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: adalimumab, anakinra, antimalarial drugs, azathioprine, ciclosporin, corticosteroids, cyclophosphamide, etanercept, infliximab plus methotrexate, leflunomide, methotrexate (alone; or plus sulfasalazine plus hydroxychloroquine), oral gold, parenteral gold, penicillamine, sulfasalazine.
17067220 [Prosthetic knee infection caused by Listeria monocytogenes in a woman with rheumatoid art 2006 Jun Listeria are gram-positive bacilli that can be isolated from soil and in the normal fecal flora of many mammals. It is a uncommon pathogen in the general population, but immunocompromised individuals can develop several focal infections, most notably meningoencephalitis and sepsis. Nevertheless, infectious arthritis caused by Listeria monocytogenes is a exceptional event. We report a new case of prosthetic knee arthritis due to Listeria in a woman with seropositive rheumatoid arthritis and Waldenström s macroglobulinemia receiving prednisone and methotrexate. In addition, we review the literature on listeria joint infections.
16436492 The effect of infliximab on bone metabolism markers in patients with rheumatoid arthritis. 2006 Jun OBJECTIVE: The aim of this study was to evaluate urinary excretion of N-telopeptide of type I collagen (NTX) and deoxypyridinoline (DPD), markers of bone resorption, and serum bone alkaline phosphatase (BAP) level, a marker of bone formation and an early marker of osteoblast differentiation, in patients with rheumatoid arthritis (RA) treated with infliximab. METHODS: Seventeen male and female patients (age 60.7+/-2.53 yr; mean disease duration 12.9+/-3.01 yr; Steinbrocker's class II-IV) with RA, diagnosed according to the criteria of the American College of Rheumatology (ACR), took part in the study between March 2003 and January 2005. None of the patients had a history of oestrogen replacement therapy. All patients were treated with infliximab combined with methotrexate. Infliximab was infused intravenously at 3 mg/kg at baseline, 2 and 6 weeks, then every 8 weeks. To evaluate disease activity, ESR, CRP, the numbers of swollen and tender joints, modified Stanford Health Assessment Questionnaire (mHAQ) score and ACR score were measured. Levels of NTX and DPD in urine and BAP in serum were measured in all patients. RESULTS: ESR, CRP, the number of swollen joints and tender joints, and mHAQ score had decreased significantly 6 weeks after initial treatment and were still low 6 months after initial treatment. NTX levels had decreased significantly 6 weeks after the initial treatment and were still low 6 months after initial treatment. DPD levels had decreased 6 months after initial infusion. Mean serum BAP level did not differ significantly among the three time points. NTX levels were statistically corresponding with the number of swollen joints and mHAQ scores. DPD levels were statistically lower corresponding with ESR. CONCLUSION: Infliximab therapy may inhibit generalized bone loss in patients with RA. NTX is a more sensitive marker than DPD.
18537958 Approaches to the treatment of early rheumatoid arthritis with disease-modifying antirheum 2008 Aug This paper reviews recent approaches to treatment of early rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs (DMARDs). The literature on treatment the early RA published between 1995 and 2007 was accessed through the PubMed database from the National Library of Medicine. Keywords were 'early rheumatoid arthritis', 'disease-modifying antirheumatic drugs', 'biologic agents' and 'combination therapy'. Only results of trials on human subjects that directly measured the effects of DMARDs or biological agents on clinical, laboratory parameters and radiological progression of early RA were selected. Combination therapy suppresses RA activity and radiological progression more effectively than monotherapy. If better control of RA is evident after 3-6 months of treatment with the combination of DMARDs, one must still decide whether to stop the first DMARD, stop the second, or continue with the combination. Combination therapy biological agents (infliximab, adalimumab) with methotrexate and etanercept therapy alone may induce remission in many patients with early RA. It is a method of choice in patients with an adverse prognosis. The main indications for combination therapy 'standard' DMARDs or combination 1 DMARDs with a biological agent are such variables as detection of a shared epitope, increase of concentration of anticyclic citrullinated peptide antibodies, rheumatoid factor, C-reactive protein, 28-joint disease activity score, Sharp score and presence of erosion in joints. The majority of rheumatologists believe that patients with RA should be treated with DMARDs earlier rather than later in the disease process. Further trials should establish the optimal approaches to early RA therapy.
17922624 The anti-inflammatory effect of A3 adenosine receptor agonists: a novel targeted therapy f 2007 Oct Targeting the A(3) adenosine receptor (A(3)AR) to combat inflammation is a new concept based on two findings. First, A(3)AR is highly expressed in inflammatory cells, whereas low expression is found in normal tissues. This receptor was also found to be overexpressed in peripheral blood mononuclear cells, reflecting receptor status in the remote inflammatory process. Second, A(3)AR activation with a specific agonist induces de-regulation of the NF-kappaB signaling pathway in inflammatory cells, as well as initiation of immunomodulatory effects. The A(3)AR agonist CF-101 (known generically as IB-MECA) induces anti-inflammatory effects in experimental animal models of collagen- and adjuvant-induced arthritis. Combined therapy with CF-101 and methotrexate in adjuvant-induced arthritis rats yielded an additive anti-inflammatory effect. Methotrexate induced upregulation of A(3)AR, rendering the inflammatory cells more susceptible to CF-101. In Phase I and in Phase IIa human studies, CF-101 was safe, well tolerated and showed strong evidence of an anti-inflammatory effect in rheumatoid arthritis patients. In peripheral blood mononuclear cells withdrawn from the patients at base line, a statistically significant correlation between A(3)AR expression level and response to the drug was noted. It is suggested that A(3)AR may serve as a biologic marker to predict patient response to the drug. Taken together, this information suggests that A(3)AR agonists may be a new family of orally bioavailable drugs to be developed as potent inhibitors of autoimmune-inflammatory diseases.
16219644 Significance of SAA1.3 allele genotype in Japanese patients with amyloidosis secondary to 2006 Jan OBJECTIVE: To clarify the clinical significance of the SAA1.3 allele in the development and outcome of AA amyloidosis in Japanese patients with rheumatoid arthritis (RA). METHODS: One hundred and twenty RA patients (60 alive and 60 dead) fulfilling the 1987 ACR criteria and 62 RA patients with biopsy-confirmed amyloid A (AA) amyloidosis (36 alive and 26 dead) were enrolled. The SAA1 genotypes were determined by PCR-based restriction fragment length polymorphism. To predict the clinical outcome of AA amyloidosis, we investigated characteristics and survival, focusing on the SAA1.3 allele retrospectively. RESULTS: The SAA1.3 allele genotype was not only a risk factor for the association of AA amyloidosis but also a poor prognostic factor for the development of AA amyloidosis (P=0.015). Both the association of AA amyloidosis arising early in the RA disease course and symptomatic variety and severity were found in amyloidotic patients with the SAA1.3 allele. The presenting factors adversely influenced were age (P=0.001), lowered serum albumin (P=0.001) and creatinine concentration (P=2.14 x 10(-5)). Renal involvement was associated with poor survival in patients with AA amyloidosis (P=0.011) and the presence of cardiac involvement was likely to be a risk factor for survival (P=0.062). The rate of the causes of death in respect to the category of infection, gastrointestinal diseases, and renal failure was higher in patients with AA amyloidosis than in those without amyloidosis, gastrointestinal diseases and renal failure. Cyclophosphamide was found to be superior to methotrexate in the management of RA patients with AA amyloidosis. CONCLUSION: Our data support the fact that homozygosity for the SAA1.3 allele is a univariate predictor of survival in addition to a risk factor for the association of AA amyloidosis adversely influencing the outcome in Japanese RA patients. Renal involvement is a pivotal clinical manifestation in the development of AA amyloidosis, as is likely to be cardiac involvement in AA amyloidosis secondary to RA.
19078861 [Is the response to anti-TNFalpha treatment influenced by the presence of IgM rheumatoid f 2008 Oct AIM: To verify if the response to TNFalpha inhibitors is influenced by the presence of IgM rheumatoid factor (RF), in patients with RA. MATERIAL AND METHODS: In this study, the patients with the diagnosis of RA treated with TNFa inhibitors followed in our hospital were recruited. A protocol was applied including demographic, clinical and laboratory data, in order to calculate DAS 28. The presence/absence of IgM RF and associated therapies were record. RESULTS: Fifty-seven patients, 52 female, with a mean duration of anti-TNFa treatment of 30,9+/-15,9 months were studied. Twenty-four patients were being treated with infliximab, 17 with adalimumab and 16 with etanercept. Forty-one patients had IgM RF detectable in serum (RF positive group). In the RF positive group, the variation of DAS 28 was -1,75 +/- 1,53 vs -1,04 +/- 1,76 in the RF negative group (p=0,135). The mean duration of anti-TNFalpha treatment was similar in both groups (31,9+/-15,9 vs 29,5+/-16,16 months). Patients who were treated with methotrexate presented a higher variation of DAS 28 (-1,87 +/- 1,70 vs -0,80 +/- 1,09; p=0,041) and this variation was dose dependent (p=0,056). CONCLUSIONS: Despite needing a replication in a larger cohort, our results suggest that the presence of IgM RF in the serum did not interfere with the response to treatment with TNFalpha inhibitors.
17567634 Trends in medication and health-related quality of life in a population-based rheumatoid a 2007 Aug OBJECTIVES: To study trends in treatment, health status and health-related quality of life (HRQL) in two cross-sectional surveys over a 5-yr period and in an observational follow-up sub-cohort based on a population-based rheumatoid arthritis (RA) register in Malmö, Sweden. MATERIAL AND METHODS: A continuously updated population-based RA register was established in Malmö city in southern Sweden in 1997. Patient-administered questionnaires in 1997 and 2002 were used to collect information on demographics, medication and health status. Cross-sectional comparisons were made between 1997 and 2002. A longitudinal analysis was also performed in the RA patients participating in both surveys. RESULTS: Increased proportions of patients were treated with disease-modifying anti-rheumatic drugs (DMARDs) (69 vs 52%), corticosteroids (30 vs 23%), methotrexate (52 vs 29%) and biologics (14 vs 0%) in 2002 compared with 1997. In the cross-sectional analysis, the visual analogue scores (VAS) for pain and general health and the short form 36 (SF-36) domains were slightly better in 2002 than in 1997. In the observational sub-cohort, patients treated with biologics improved significantly in several measures of health status, whereas those starting on methotrexate or undergoing other or no changes in DMARD therapy did not. CONCLUSIONS: In this population-based RA cohort, patients were more actively treated in 2002. Small improvements were seen in health status and these improvements were exclusively attributable to treatment with biologics.
17478469 Anti-rheumatic drug use and risk of serious infections in rheumatoid arthritis. 2007 Jul OBJECTIVES: To assess the risk of severe infections associated with the use of traditional disease-modifying anti-rheumatic drugs (DMARDs) and glucocorticoid agents in rheumatoid arthritis (RA). METHODS: Our study was a case-control design nested within a cohort of 23 733 RA patients studied between 1 January 1980 and 31 December 2003. Matching on age and gender, and adjusting for comorbidity and physician use, conditional logistic regression was used to estimate the effect of specific drugs on the rate ratio (RR) for infections requiring hospitalization. RESULTS: The risk for all infections requiring hospitalization appeared to be most elevated with current exposures to cyclophosphamide [RR: 3.26, 95% confidence interval (CI): 2.28-4.67] and systemic glucocorticoid agents (RR: 2.56, 95% CI: 2.29-2.85); azathioprine was associated with a moderate increased risk (RR: 1.52, 95% CI: 1.18-1.97). There was a suggestion of increased risk of pneumonia due to methotrexate (RR: 1.16, 95% CI: 1.02-1.33). The results were similar for the period before and after the introduction of anti-tumour necrosis factor (TNF) agents. The RR point estimate for anti-TNF agents suggested about a 2-fold increased risk for all infections, but the estimate was imprecise. CONCLUSIONS: In this large cohort of RA patients, the most heightened risk of serious infections was seen with the use of glucocorticoid agents and immunosuppressive DMARDs. Assessments of infection risk related to newer and emerging therapies should carefully consider concomitant medication exposures, including traditional DMARDs and glucocorticoid therapy.
17888215 Multiplex serum cytokine monitoring as a prognostic tool in rheumatoid arthritis. 2007 Jul OBJECTIVE: Early optimized therapy of rheumatoid arthritis (RA) results in improved outcomes. The initiation of optimized therapy is hindered by the difficulty of early diagnosis and the limitations of current disease activity and therapeutic response assessment tools. Identifying patients requiring early combination DMARD/biologic therapy is currently a significant clinical challenge given the lack of definitive prognostic criteria. Since cytokines are soluble intracellular signaling molecules that modulate disease pathology in RA, we tested the recent conjecture that en mass serum cyto-kine measurement and monitoring will provide a useful tool for effective therapeutic management in RA. METHODS: We assayed the levels of 16 serum cytokines in 18 RA patients treated prospectively with methotrexate and from 18 unaffected controls. Specific mechanistic aspects of inflammatory pathology in the periphery could be discerned on a patient-specific basis from patients' serum cytokine profiles, information that may aid in the design of anti-cytokine biologic therapy. A serum Cytokine Activity Index (CAI) was also created using multi-variant analysis methods. RESULTS: Distinct cytokines were significantly elevated in RA patients relative to controls, and three distinct clusters with correlations to disease activity were identified. The Cytokine Activity Index correlated well with the therapeutic res-ponse; responders and non-responders in this cohort were distinguishable as early as one month post initiation of methotrexate therapy, well before clinical assessments of response are commonly completed. CONCLUSION: Clinical assessment tools could be derived from this approach that may provide a means to continually track patients, allowing intervention strategies to be better evaluated on a patient-specific basis and to identify residual cytokine activity that could be used to guide combination therapy.
18578967 Tumor necrosis factor alpha inhibitors, methotrexate or both? An inquiry into the formal e 2008 May OBJECTIVE: The relative high cost and potential side effects mandate careful scrutiny as to when tumor necrosis factor alpha (TNF) inhibitors should be used in everyday practice. We surveyed how TNF inhibitors performed in randomized controlled trials when compared to methotrexate in methotrexate naive rheumatoid arthritis patients. METHODS: We identified all randomized controlled trials with TNF inhibitors and methotrexate. We surveyed A-whether the patients enrolled were methotrexate naive or not; B-efficacy outcomes and C-radiographic outcomes. RESULTS: Four studies that had been reported to be conducted among metho-trexate naive patients were identified. TEMPO trial was not done entirely in methotrexate naive patients, contrary to what has been reported by its authors. Among these studies the methotrexate naive arms did as well as the TNF inhibitor alone. The combination was better than either drug alone. Among the 6 studies in which the methotrexate failure patients had been enrolled, the TNF inhibitors always performed better when analyzed head to head with the methotrexate alone arms. CONCLUSIONS: Available data indicate that TNF inhibitors are superior to solo methotrexate use only in the setting of combination treatment.
17265478 A prediction rule for disease outcome in patients with recent-onset undifferentiated arthr 2007 Feb OBJECTIVE: In patients with undifferentiated arthritis (UA), methotrexate is effective for inhibiting symptoms, structural damage, and progression to rheumatoid arthritis (RA). However, 40-50% of patients with UA experience spontaneous remission. Thus, adequate decision-making regarding treatment of patients with early UA requires identification of those patients in whom RA will develop. METHODS: A prediction rule was developed using data from the Leiden Early Arthritis Clinic, an inception cohort of patients with recent-onset arthritis (n = 1,700). The patients who presented with UA were selected (n = 570), and progression to RA or another diagnosis in this group was monitored for 1 year of followup. The clinical characteristics with independent predictive value for the development of RA were selected using logistic regression analysis. The diagnostic performance of the prediction rule was evaluated using the area under the curve (AUC). Cross-validation controlled for overfitting of the data (internal validation). An independent cohort of patients with UA was used for external validation. RESULTS: The prediction rule consisted of 9 clinical variables: sex, age, localization of symptoms, morning stiffness, the tender joint count, the swollen joint count, the C-reactive protein level, rheumatoid factor positivity, and the presence of anti-cyclic citrullinated peptide antibodies. Each prediction score varied from 0 to 14 and corresponded to the percent chance of RA developing. For several cutoff values, the positive and negative predictive values were determined. The AUC values for the prediction rule, the prediction model after cross-validation, and the external validation cohort were 0.89, 0.87, and 0.97, respectively. CONCLUSION: In patients who present with UA, the risk of developing RA can be predicted, thereby allowing individualized decisions regarding the initiation of treatment with disease-modifying antirheumatic drugs in such patients.
16984942 Abatacept improves both the physical and mental health of patients with rheumatoid arthrit 2007 Feb OBJECTIVE: To examine the impact of added abatacept treatment on health related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX). METHODS: The impact of abatacept treatment on HRQoL was examined in a longitudinal, randomised double blind, placebo controlled clinical trial. Effects of treatment on HRQoL were examined using repeated measures analysis of covariance and comparing rates of change in HRQoL across treatment groups. The relationship between American College of Rheumatology (ACR) clinical markers and disease duration with changes in HRQoL indicators was also examined. Finally, a responder analysis was used to examine the percentage of patients who improved by 0.5 SD in 12 months or who reached the normative levels seen in the US general population. RESULTS: Statistically significant improvements in the abatacept group relative to controls were observed across a range of HRQoL measures, including physical function, fatigue, all eight domains of the SF-36, and the physical and mental component summaries (PCS and MCS). Improvements were seen as early as day 29 for fatigue and for five out of eight SF-36 domains. By day 169, all HRQoL measures were significantly better with abatacept than with placebo. HRQoL gains were associated with greater ACR clinical improvement, and the effects were consistent for patients with different disease duration. A significantly greater percentage of patients treated with abatacept reached normative levels of PCS, MCS, physical functioning, and fatigue compared with patients treated with MTX alone. CONCLUSION: Combined abatacept and MTX treatment produces significant improvements across a wide range of HRQoL domains in patients with RA.
17062648 Sustained benefit in rheumatoid arthritis following one course of rituximab: improvements 2006 Dec OBJECTIVES: To evaluate the long-term impact on physical function of a single course of rituximab in rheumatoid factor, seropositive patients with active rheumatoid arthritis (RA) despite ongoing methotrexate treatment. METHODS: A randomized, controlled trial comparing rituximab alone [1,000 mg intravenously (iv) on days 1 and 15, n= 40], or in combination with cyclophosphamide (750 mg iv on days 3 and 7, n= 41) or oral methotrexate (> or =10 mg/week, n= 40) with placebo + methotrexate (> or =10 mg/week, n= 40), resulted in significant reductions in disease activity at weeks 24 and 48. Sustained improvements in physical function and standard effect sizes (SES) for changes in components of ACR and EULAR criteria were evaluated over 2 yrs. RESULTS: More patients receiving rituximab + methotrexate completed a 2-yr follow-up without further treatment than those receiving placebo + methotrexate (45% vs 15%, respectively), rituximab alone (10%) or rituximab + cyclophosphamide (22%). This reflected a higher percentage of patients receiving rituximab + methotrexate reporting improvements in Health Assessment Questionnaire Disability Index > or = minimum clinically important difference at 1 and 2 yrs (68% and 30%, respectively) compared with placebo + methotrexate (28% and 15%), rituximab monotherapy (43% and 10%) or rituximab + cyclophosphamide (39% and 12%). SES were high in all rituximab groups and revealed differing patterns of response over time. CONCLUSION: A single course of rituximab with continuing methotrexate in patients with active RA provided clinically meaningful improvements in physical function over 2 yrs, with lower discontinuation rates and larger SES for improvements in ACR and EULAR criteria components.
16200383 Lethal acute respiratory distress syndrome during anti-TNF-alpha therapy for rheumatoid ar 2006 May Tumor necrosis factor alpha (TNF-alpha) blocking drugs improve therapy for rheumatic diseases, but the risk of additional immunosuppression and infection is unclear. We report on a patient with rheumatoid arthritis treated with etanercept for 2 years, in addition to methotrexate and prednyliden, who developed fulminant pneumococcal pneumonia with rapid progression to fatal acute respiratory distress syndrome (ARDS) and septic shock. In patients receiving anti-TNF-alpha therapy, especially in combination with corticosteroids, signs of pulmonary infection should be regarded as very serious, as fulminant pneumonia with ARDS and severe sepsis may develop within 24 h.
19060002 Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a syst 2009 Jul OBJECTIVE: To perform a systematic literature review of the long-term safety of methotrexate (MTX) monotherapy in rheumatoid arthritis (RA). METHODS: A search was performed in Medline, Cochrane and EMBASE. Adults with RA who had received MTX monotherapy for more than 2 years were studied. RESULTS: 88 published studies were included. Over 12 years of treatment, the termination rate of MTX due to toxicity was less than for sulfasalazine, gold, d-penicillamine and higher than for hydroxychloroquine (level of evidence 2a-2b). Long-term use of MTX does not appear to be a risk factor for serious infections, including herpes zoster (2b-4), and could provide a survival benefit by reducing cardiovascular mortality (2b). The prevalence of raised liver enzymes (more than twice the upper limit of normal) is close to 13% of patients; 3.7% of patients stopped MTX permanently owing to liver toxicity (2b). Data on the risk for liver fibrosis/cirrhosis are conflicting: a meta-analysis showed an incidence of fibrosis of 2.7% after 4 years of MTX (2a). However, two other studies on sequential liver biopsies did not show evidence for developing severe damage (2b). Insufficient data are available to fully assess the risk of lymphoma and malignancies, although there is no strong evidence of increased risk (2b-4). CONCLUSION: This systematic literature search on MTX monotherapy with relatively low-dose use during at least 2 years shows favourable long-term safety.
18045808 Recent insights in the pharmacological actions of methotrexate in the treatment of rheumat 2008 Mar This review presents recent data supporting the methotrexate (MTX) mechanisms of action, which are likely to account for its anti-proliferative and immunosuppressive effects in rheumatoid arthritis (RA). The effects of MTX in vivo may be mediated by reducing cell proliferation, increasing the rate of apoptosis of T cells, increasing endogenous adenosine release, altering the expression of cellular adhesion molecules, influencing production of cytokines, humoral responses and bone formation. Several reports indicate that the effects of MTX are influenced by genetic variants, specific dynamic processes and micro-environmental elements such as nucleotide deprivation or glutathione levels. The challenge for the future will be linking biological and genetic markers relevant to the response to MTX in RA.
17028793 Is three selected parameters adequate to monitor rheumatoid arthritis? 2007 Jun This pilot study was done to choose which among the five core set criteria will have more discriminating ability and which is easy to administer in a clinical setting. Forty-eight patients recently diagnosed to have rheumatoid arthritis (RA) were recruited for the study. They were assessed by a rheumatologist in each visit (initial and after 2 months of treatment), for five core measures: patient assessment, pain (measured on VAS scale), number of tender joints, health assessment questionnaire (HAQ) score, and erythrocyte sedimentation rate (ESR). All patients were treated with methotrexate 7.5 mg per week and hydroxychloroquin 400 mg per day with adequate dose of NSAIDs. Patients with associated conditions like stroke, ischemic heart disease, and other physical comorbidity were excluded. They were categorized as 20, 50, and 70% improvement, if four of the five criteria occur. The Wilcoxon signed rank test and discriminant function analysis were done to identify the order of importance of measures on influencing the outcome. The ESR followed by patient improvement scale showed the least changes, while HAQ showed the highest changes. Discriminate function analysis has been carried out to see which factors influenced in grouping them for responses with post hoc analyses of finding the order of importance of these factors in classifying the response. Pain scale, ESR, HAQ score, patient improvement scale, and tender score were in the decreasing value of importance. The pain scale, HAQ, and ESR, which are more objective and discriminate measures, are useful as measures in RA.
17450763 [Guidelines for the use of biologic therapies in rheumatoid arthritis--December 2006 updat 2007 Jan The authors present the revised version of the Portuguese Society of Rheumatology (SPR) guidelines for the treatment of rheumatoid arthritis (RA) with biological therapies. In these guidelines the criteria for introduction and maintenance of biological therapies were discussed as well as the contra-indications and procedures in case of non-responders. Biological treatment is indicated in RA patients with a disease activity score 28 (DAS 28) superior to 3,2 despite treatment with 20mg/week of methotrexate (MTX) for at least 3 months or, if such treatment is not possible, refractory to 6 months of other conventional disease modifying drug or combination therapy. It is also considered the hypothesis of starting a biological treatment in RA patients treated by the previous regimes with a DAS28 score between 2,6 and 3,2 and a significative functional or radiological worsening. The follow-up should be performed each 3 months. The response criteria, at the end of the first 3 months of treatment, is a decrease of 0,6 in the DAS28 score. After 6 months of treatment response criteria is defined as follows: for those with an initial DAS28 score superior to 5,1, a reduction of the DAS28 score below 4 is required; for those with an initial DAS28 score inferior to 5,1, a reduction of the DAS28 score below 2,6 or between 2,6 and 3,2 without a significative functional or radiological worsening is required. Non-responders, in accordance to the Rheumatologist's clinical opinion, should try a switch to other tumour necrosis factor alpha antagonist or to rituximab.
18034620 677C>T and 1298A>C MTHFR polymorphisms affect methotrexate treatment outcome in rheumatoid 2007 Nov INTRODUCTION: Methotrexate (MTX), widely used in the treatment of rheumatoid arthritis (RA), inhibits dihydrofolate reductase and folate-dependent enzymes. Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and has been shown to be polymorphic, affecting the enzyme activity. METHODS: To examine the association between 677C>T and 1298A>C MTHFR polymorphisms and MTX efficacy in the treatment of RA, a total of 174 RA patients, treated with MTX plus methylprednisone 4 mg and folic acid 5 mg were analyzed. RESULTS: In univariate regression analysis model, the MTHFR 677T allele was associated with significantly higher frequency of remission, whereas in the case of the 1298C allele, a tendency for higher remission rate was observed. In multivariate regression analysis, the presence of both 677T and 1298C alleles was associated with an increased frequency of remission. CONCLUSION: The results of our study suggest that the MTHFR 677T and 1298C alleles may be associated with an increased rate of RA remission in patients treated with MTX receiving high doses of folic acid supplementation.