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ID PMID Title PublicationDate abstract
20421345 Patients with RA in remission on TNF blockers: when and in whom can TNF blocker therapy be 2010 Sep OBJECTIVES: Combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockade has increased remission rates in patients with rheumatoid arthritis. However, there are no guidelines regarding cessation of therapy. There is a need for markers predictive of sustained remission following cessation of TNF blocker therapy. METHODS: Patients in remission (DAS28 <2.6) treated with a TNF blocker and MTX as initial or delayed therapy were recruited. Joints were assessed for grey scale synovitis and power Doppler (PD) activity. Immunological assessment involved advanced six-colour flow cytometry. RESULTS: Of the 47 patients recruited, 27 had received initial treatment and 20 delayed treatment with TNF blocking drugs. Two years after stopping TNF blocker therapy, the main predictor of successful cessation was timing of treatment; 59% of patients in the initial treatment group sustained remission compared with 15% in the delayed treatment group (p=0.003). Within the initial treatment group, secondary analysis showed that the only clinical predictor of successful cessation of treatment was shorter symptom duration before receiving treatment (median 5.5 months vs 9 months; p=0.008). No other clinical features were associated with successful cessation of therapy. Thirty-five per cent of patients had low PD activity but levels were not informative. Several immunological parameters were significantly associated with sustained remission including abnormal differentiation subset of T cells and regulatory T cells. Similar non-significant trends were observed in the delayed treatment group. CONCLUSION: In patients in remission with low levels of imaging synovitis receiving combination treatment with a TNF blocker and MTX, immunological parameters and short duration of untreated symptoms were associated with successful cessation of TNF blocker therapy.
19116965 Patient-reported outcomes in a randomized trial comparing four different treatment strateg 2009 Jan 15 OBJECTIVE: To investigate the effectiveness of 4 different treatment strategies for recent-onset rheumatoid arthritis (RA) on 2-year patient-reported outcomes, including functioning and quality of life. METHODS: A total of 508 patients with recent-onset RA were randomly assigned to 1) sequential monotherapy, 2) step-up combination therapy, both starting with methotrexate, 3) initial combination therapy, including a tapered high-dose prednisone, or 4) initial combination therapy with methotrexate and infliximab. Treatment was adjusted every 3 months if the Disease Activity Score (DAS) remained >2.4. The McMaster Toronto Arthritis Patient Preference Disability Questionnaire, the Short Form 36 (SF-36), and scores for pain, global health, and disease activity measured on a 100-mm visual analog scale (VAS) were compared between groups at baseline and every 3 months thereafter for 2 years. RESULTS: After 2 years, all patient-reported outcomes had improved significantly from baseline, irrespective of the treatment strategy. SF-36 subscale scores approached population norms for 3 physical components, and achieved population norms (P > 0.05) for bodily pain and 4 mental components. Improvement in functioning, VAS scores, and physical items of the SF-36 occurred significantly earlier in patients treated with initial combination therapies (all comparisons after 3 months: overall P < 0.001; P < 0.05 for groups 1 and 2 versus groups 3 and 4). CONCLUSION: All 4 DAS-driven treatment strategies resulted in substantial improvements in functional ability, quality of life, and self-assessed VAS scores after 2 years. Initial combination therapy led to significantly faster improvement in all patient-reported measures.
19757979 Pattern differentiation in Traditional Chinese Medicine can help define specific indicatio 2009 Sep OBJECTIVES: The objective of this study is to explore the role of Traditional Chinese Medicine (TCM) pattern differentiation in identifying a subset of patients with rheumatoid arthritis (RA) who are more likely to respond to biomedical combination therapy. METHODS: This study uses data from a previous multicenter randomized-controlled clinical trial. One hundred and ninety-four (194) patients were treated with biomedical combination therapy (diclofenac, methotrexate, and sulfasalazine). ACR20 response at 12 weeks and 24 weeks was used for evaluation of efficacy. Eight (8) symptoms, which are the most important for establishing TCM cold and hot patterns in patients with RA, were analyzed in this study. TCM patterns were obtained using factor analysis of the eight symptoms. Thirst, vexation, hot feeling in the joints, turbid yellow-colored urine, and fever were classified as factor 1. Cold feeling in the whole body, cold feeling in the limbs, and cold feeling in the joints were classified as factor 2. The classification into factor 1 and 2 is similar to TCM hot pattern and cold pattern differentiation, since the symptoms in factor 1 and 2 are the key symptoms in TCM hot and cold patterns, respectively. The effective rates in patients with different TCM patterns were analyzed with the chi(2) method. RESULTS: At 12 weeks, ACR20 response in patients treated with the biomedical combination therapy was 36.08%. At 24 weeks, ACR20 response was 69.59%. Based on the eight symptoms used in factor analysis, the effective rates in the patients with cold pattern and hot pattern were 51.67% and 29.09%, respectively, after 12 weeks of treatment; and 88.52% and 55.36%, respectively, after 24 weeks of treatment. CONCLUSIONS: TCM pattern differentiation based on symptoms can help identify a subset of patients with RA that will more likely respond to biomedical therapy, consisting of diclofenac, methotrexate, and sulfasalazine.
20136356 Functional polymorphisms and methotrexate treatment outcome in recent-onset rheumatoid art 2010 Feb AIMS: Clinical response to methotrexate (MTX) treatment differs among rheumatoid arthritis patients. Genetic variation can partly account for this phenomenon. In this study, functional polymorphisms in genes related to the mechanism of action of MTX or immunopathogenesis of rheumatoid arthritis were studied for association with treatment outcome in a Dutch cohort of patients with early rheumatoid arthritis. Furthermore, tests for replication of previous research on these genetic variants were performed according to reported end points. MATERIALS & METHODS: Seven polymorphisms in seven genes were analyzed in 205 genotyped patients with active rheumatoid arthritis. All patients received standardized MTX treatment (< or =25 mg per week orally) combined with folic acid. MTX treatment outcome was evaluated by disease activity score criteria and adverse drug events. The following genetic variants were analyzed and correlated: ABCB1 3435C>T, ITPA IVS2 +21A>C, HLA-G (-14 bp >+14 bp), TGFB1 +869T>C and TLR4 +896A>G. In case of significant differences, regression analyses were applied. Since carriers of the minor alleles of the SNPs DHFR 829C>T and IMPDH2 +787C>T were not observed, no statistical analyses could be performed. RESULTS: No significant associations or replications of these genetic variants with MTX efficacy were demonstrated. Regarding toxicity, patients carrying the ABCB1 3435T-allele and TLR4 +896G-allele were 2.5-times more likely to develop adverse drug events at 6 months (odds ratio: 2.6; 95% CI: 1.1-6.2, and odds ratio: 2.5; 95% CI: 1.1-6.1, respectively). Additionally, this chance increased almost fourfold in patients with the two unfavorable genotypes (odds ratio: 3.9; 95% CI: 1.5-10.3). However, none of these associations remained significant after correction for multiple testing (p < 0.004). CONCLUSION: Our data indicate that MTX toxicity was potentially associated with ABCB1 3435C>T and TLR4 +896A>G. However, after correction, none of these associations remained significant. Furthermore, no significant associations or replications of these functional variants with efficacy were found.
20622199 Population approach for exposure-response modeling of golimumab in patients with rheumatoi 2011 May Golimumab is a human immunoglobulin G1κ monoclonal antibody that binds with high affinity and specificity to tumor necrosis factor-α. The objective of this study was to establish an approach for exposure-response modeling for golimumab in patients with rheumatoid arthritis using the American College of Rheumatology index of improvement (ACRN) as a measure of change in disease severity. Data were collected from 302 patients in the phase III GO-FORWARD trial who received golimumab or placebo plus methotrexate (background therapy) every 4 weeks through week 52. A latent-variable (unobservable) approach was used with an inhibitory indirect response model to link the placebo (methotrexate) effect and golimumab concentrations to ACRN scores. A model parameterization was proposed to allow deterioration beyond baseline and maintain mechanistic interpretability of the population-based indirect response model. The modeling was conducted using a sequential pharmacokinetic/pharmacodynamic approach. None of the covariate factors evaluated (demographics, disease characteristics, comorbidities, or concomitant medications) significantly improved the model fits. Likelihood profiling and a bootstrap analysis were used to assess parameter estimation precision, with their suitability discussed. The approach can be readily extended to model other types of clinical (efficacy or safety) scores with either an upper or a lower boundary.
19578852 Prevalence of positive ppd in a cohort of rheumatoid arthritis patients. 2010 Mar The main objective of this study is to determine the prevalence of positive and anergic tuberculin skin test (ppd) in a rheumatoid arthritis cohort of patients (RA) and assess the association among ppd results and clinical and treatment variables. Patients with RA diagnosis were included. The ppd was done by Mantoux method. Positive result was considered when indurations were equal or greater than 5 mm. Anergic reaction was defined when the indurations was 0 mm. We included 105 patients (N = 105). The prevalence of positive ppd was 12.4% (n = 13), while the 87.6% (n = 92) presented a negative result. The 69.5% (n = 73) of the population were anergic to ppd. Patients with negative result received higher steroids dosages than patients with positive ppd (p < 0.04). In the multivariable model, the steroids dosage was a significant and independent predictor of negative ppd (p = 0.021, OR 0.72, 95% CI 0.55-0.95). Anergic and non-anergic patients were separated in groups, and a new analysis was done. The higher dosage of methotrexate was associated to tuberculine anergy (p = 0.025). In the multivariable model, the methotrexate dosage was a significant and independent predictor of tuberculine anergy (p = 0.005, OR 1.14, 95% CIs 1.04-1.24). In conclusion, in our cohort, the prevalence of positive ppd was lower than others studies. Among analyzed variables, the high steroid dose was a significant and independent predictor of negative ppd. The methotrexate treatment and dose were associated with ppd anergy.
19917174 A systematic review on the optimum management of the use of methotrexate in rheumatoid art 2009 Sep OBJECTIVE: To examine the use of metho-trexate (MTX) in rheumatoid arthritis (RA) patients during the perioperative period. METHODS: Systematic review of studies retrieved by a sensitive search strategy in Medline (1961-July 2007), Embase (1961-July 2007), Cochrane Library (up to July 2007), and from the abstracts of the ACR (2005, 2006) and EULAR (2005-2007) annual scientific meetings. SELECTION CRITERIA: (population) studies had to include patients with RA undergoing surgery; (intervention and control) studies had to test continuing MTX versus stopping MTX; and (outcomes), studies had to report complications within a year after the surgery including infections, wound morbidity, surgery complications, and RA flares. Only randomized controlled trials (RCT) or high quality cohort studies with a control group were included. RESULTS: Patients from the four included studies were mostly women with mean ages around 60. All of them underwent elective orthopaedic surgery and were taking MTX doses mainly from 5 mg/week to 10 mg/week. By order of level of evidence, we found two RCTs, in which continuing on MTX was not associated with increasing risk of surgery complications, but it was statistically associated with less RA flares. In a prospective cohort study, four infections were observed in the MTX group while none were observed in the control group. No disease flare was reported in any group. A retrospective study showed that patients on MTX reported fewer cases of wound morbitity (p=0.038), RA flares (p=0.050), and no differences related to infections compared to those who stopped MTX. CONCLUSIONS: Continuing with low doses of MTX seems to be a safe option during the perioperative period in RA patients without relevant comorbidities and/or risk factors of infections, undergoing elective orthopaedic surgery, while maintaining disease control.
20863444 Associations between the genetic polymorphisms of MTHFR and outcomes of methotrexate treat 2010 Sep OBJECTIVES: To determine whether 5, 10-methylenetetrahydrofolate reductase (MTHFR) rs1801133C/T, rs1801131A/C, rs2274976A/G, rs2066462C/T genetic polymorphisms are associated with clinical response and adverse effects (AEs) of methotrexate (MTX) treatment in Chinese Han patients with rheumatoid arthritis (RA). METHODS: One hundred and ten RA patients defined by the American College of Rheumatology (ACR) 1987 revised criteria were involved in this study. All patients were treated with low-dose MTX (10-15 mg/week) without concomitant uses of other DMARDs. Clinical response (using ACR20 criteria) and AEs were evaluated at 0, 4, 12, 16 and 24 weeks. The genotypes of MTHFR rs1801133C/T, rs1801131A/C, rs2274976A/G and rs2066462C/T were detected by real-time fluorescent quantitative PCR. RESULTS: The allele frequency of rs1801131C in the clinical response group was higher than in the non-response group (21.0% vs. 8.1%, p<0.05), and the patients with CC or AC genotype had greater clinical response than those with AA genotype. The allele frequencies of rs1801133T and rs2274976A were higher in the group with AEs than that without AEs (56.4% vs. 37.5% and 14.9% vs. 4.2%, respectively, both p<0.05). The patients with CT or TT genotype in rs1801133 had higher risks of AEs than those with CC genotype. CONCLUSIONS: While rs1801131A/C genetic polymorphism is associated with the clinical response, rs1801133C/T and rs2274976A/G genetic polymorphisms are associated with MTX-related AEs in the treatment of RA. This suggests individualisation is necessary to achieve optimal outcomes in MTX therapy of RA.
20140758 Methotrexate treatment in rheumatoid arthritis: management in clinical remission, common i 2010 Jun This work was performed as part of the Portuguese participation in the 3E Initiative 2007-2008, dedicated to the use of methotrexate (MTX) in rheumatic conditions. Three questions raised by Portuguese rheumatologists and considered relevant to clinical practice remained out of the selection of a set of ten key questions formulated to further establish multinational recommendations on the use of MTX in rheumatic diseases. The authors collected and analyzed all the evidence available by using a systematic literature search methodology and selection criteria concerning the following issues in rheumatoid arthritis (RA): (1) the management of MTX after clinical remission; (2) the management of MTX during infections and (3) the screening and treatment of tuberculosis in patients on MTX treatment. A total of 1,862 references were identified, of which 163 were selected for detailed analysis and 12 included in the final review. The evidence was appraised according to the Oxford Centre for Evidence-based Medicine (EBM) levels of evidence. Although with limited evidence, the authors concluded that: (1) extending the interval for MTX therapy may be a valid alternative regimen in a subset of RA patients in clinical remission (EBM level 2b); (2) MTX may be safe during some common infections in RA patients (EBM level 3b/4); (3) screening and treatment of TB in patients on MTX should be similar to the general population (EBM level 4). The evidence available to support clinical decisions in this area is very limited in number and quality. There is a need for further research and while that is unavailable, practical decisions have to rely on experience and expert opinion.
19526307 Leflunomide-induced polymyositis in a patient with rheumatoid arthritis. 2009 Although rheumatoid arthritis (RA) and myositis are major autoimmune diseases, co-occurrence of the two is rare. We treated a patient who developed polymyositis (PM) following the treatment of RA with leflunomide. Prednisolone (PSL) in combination with methotrexate (MTX) was effective in managing the PM, but the RA relapsed during the treatment. Based on the clinical course, we suspect that the PM was induced by the leflunomide treatment and suggest that clinicians should consider the possibility of this rare adverse event in cases of cholestyramine-resistant elevation of transaminases.
20552247 Efficacy and safety of tacrolimus in 101 consecutive patients with rheumatoid arthritis. 2010 Oct The objective of this study was to assess the usefulness of tacrolimus (TAC) for rheumatoid arthritis (RA) patients. The first 101 consecutive RA patients in whom TAC treatment was initiated were prospectively registered and their data analyzed. Clinical variables were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) database. The 101 patients included 85 females and 16 males. Average doses of TAC were 1.62 mg/day at entry and 2.13 mg/day at month 12. The average doses of concomitantly prescribed prednisolone (6.92 mg/day) and methotrexate (MTX; 8.59 mg/week) were higher than those in all RA patients in the IORRA cohort. At month 12, 57 patients remained on TAC therapy; 18 patients had discontinued TAC due to side effects, and 16 patients had discontinued due to inefficacy. Adverse reactions responsible for discontinuation included gastrointestinal symptoms, renal dysfunction, and infection. According to the European League Against Rheumatism (EULAR) response criteria, 56.5% of the patients who continued TAC at 12 months experienced "good" or "moderate" responses. Through the use of last observation carried forward (LOCF) methodology, the average Disease Activity Score (DAS) 28 significantly improved. We confirmed the usefulness of TAC for the treatment of RA and found that TAC is suitable for RA patients who are unable to use biologic agents or to tolerate a high dose of MTX because of their complications or background factors.
20447320 Clinical effectiveness of biologics in clinical practice. 2010 TNF inhibitors are currently considered both effective and cost-effective in patients with active rheumatoid arthritis (RA), particularly in patients who have not responded fully to methotrexate. There is substantial doubt about the cost-effectiveness of TNF inhibitors as initial treatment for active RA. New data from the National Data Bank for Rheumatic Diseases now question the current consensus in methotrexate failures. The data suggest that in routine clinical practice TNF inhibitors provide only modest incremental benefits over best conventional therapy. If confirmed, these observational studies suggest that the economic argument underpinning the widespread use of TNF inhibitors in established RA is unsustainable.
18823645 Treatment with infliximab plus methotrexate improves anemia in patients with rheumatoid ar 2009 Oct OBJECTIVE: To evaluate the effect of antitumor necrosis factor-alpha monoclonal antibody infliximab treatment on anemia in patients with rheumatoid arthritis (RA). METHODS: Data from patients with RA who received infliximab or placebo in the multicenter, placebo-controlled, double-blind, randomized ATTRACT, ASPIRE, and START studies were included in this post-hoc, pooled analysis. Infliximab (3 to 10 mg/kg) was administered every 4 or 8 weeks, and all patients received stable doses of methotrexate (MTX). We determined the percentage of anemic patients (baseline hemoglobin level <12 g/dL) who had an increase from baseline in hemoglobin level greater than or equal to 1 or 2 g/dL or achieved normal hemoglobin level at week 22. The association of improvement in anemia with improvement in clinical parameters was also evaluated. RESULTS: Among patients with anemia at baseline, infliximab plus MTX treatment produced a significantly greater mean (standard deviation) increase in hemoglobin level from baseline to week 22 (0.74 [1.12], P < 0.0001) than placebo plus MTX (0.30 [0.92]). Significantly (P < 0.001) greater proportions of anemic patients treated with infliximab plus MTX had either at least a 1 g/dL (40%) or at least a 2 g/dL (12%) increase in hemoglobin level from baseline to week 22 or achieved normal hemoglobin level (43%) when compared with placebo plus MTX (19, 5, and 28%, respectively). Greater improvement in hemoglobin level among infliximab plus MTX-treated patients was consistently observed across subgroups and in patients without clinical response (American College of Rheumatology 20% response criteria) at week 22. Multiple regression analysis indicated that the effect of infliximab plus MTX on anemia was independent of improvement in disease activity. CONCLUSION: Treatment with infliximab plus MTX significantly improved hemoglobin level among anemic RA patients when compared with treatment with placebo plus MTX, even after adjusting for improvement in disease activity.
19440813 Effects of low-dose mizoribine pulse therapy in combination with methotrexate in rheumatoi 2009 The aim was to determine the efficacy of low-dose intermittent pulse administration of mizoribine (MZR), a purine synthesis inhibitor, in combination with methotrexate (MTX) to control the symptoms of rheumatoid arthritis (RA) in patients with an insufficient clinical response to MTX alone. Twenty-seven patients with active RA, despite treatment with MTX, were enrolled and given MZR in combination with MTX and continued for 24 weeks. The primary endpoint was assessment of clinical improvements using the European League against Rheumatism (EULAR) criteria. Administering MZR to RA patients with an insufficient response to MTX produced significant improvements in the Disease Activity Score 28 (DAS28) after 8-24 weeks. In addition, after 24 weeks, 60.0% and 8.0% of patients had achieved moderate and good responses, respectively, and there were significant reductions in Modified Health Assessment Questionnaire and serum matrix metalloproteinase-3 levels. The present preliminary study suggests that low-dose MZR in combination with MTX is well tolerated and provides both clinical and economic benefits.
21109516 Tumour necrosis factor antagonist use and associated risk reduction of cardiovascular even 2011 Apr OBJECTIVE: To examine the association of cardiovascular events with tumour necrosis factor (TNF) α antagonist use compared with non-biological disease-modifying antirheumatic drug (DMARD) utilisation in patients with rheumatoid arthritis (RA). METHODS: The study population included 10 156 patients enrolled in the Consortium of Rheumatology Researchers of North America RA registry. Three study cohorts were defined based on three mutually exclusive drug use categories, including TNF antagonists, methotrexate and other non-biological DMARDs. HR were calculated adjusting for cardiovascular risk factors, RA disease characteristics and prednisone use. The primary study outcome was a composite of non-fatal myocardial infarction (MI), transient ischaemic attack (TIA) or stroke and cardiovascular-related death. RESULTS: There were 88 cardiovascular events, including 26 MI, 45 TIA/strokes and 17 cardiovascular-related deaths. After adjusting for age, gender, cardiovascular risk factors and RA disease characteristics, patients using a TNF antagonist experienced a reduced risk of the primary composite cardiovascular endpoint (HR 0.39, 95% CI 0.19 to 0.82) compared with users of non-biological DMARDs. Methotrexate was not associated with a reduced risk (HR 0.94, 95% CI 0.49 to 1.80). Prednisone use was associated with a dose-dependent increased risk (p=0.04). The risk reduction associated with TNF antagonists was also observed for non-fatal cardiovascular events (HR 0.35, 95% CI 0.16 to 0.74). CONCLUSION: TNF antagonist use was associated with a reduced risk of cardiovascular events in patients with RA.
20711094 From a neutrophilic synovial tissue infiltrate to a challenging case of rheumatoid arthrit 2010 Apr The herein report illustrates how a synovial tissue heavily infiltrated by neutrophils in the first weeks of arthritis, can evolve in few months to a synovial infiltration by lymphocytes with a characteristic pattern of rheumatoid arthritis (RA). This observation suggests a critical initial role of neutrophils in RA onset, which is eventually surpassed by the activation of the adaptive immune system. In addition, this patient, despite the absence of rheumatoid factors and anti-cyclic citrullinated peptide antibodies, progressed to a highly destructive and disabling disease, that was only controlled adequately with rituximab, due to the lack of response to methotrexate and serious adverse effects with TNF blockers therapy.
19531759 A followup study of asymptomatic carriers of Pneumocystis jiroveci during immunosuppressiv 2009 Aug OBJECTIVE: To examine the preventive effects of prophylaxis against Pneumocystis jiroveci-induced pneumonia (PCP) in patients receiving immunosuppressive therapy for rheumatoid arthritis (RA) who are colonized by this organism. METHODS: We performed molecular testing by polymerase chain reaction (PCR) for P. jiroveci on induced sputum or bronchoalveolar lavage fluids of 82 patients with RA. During primary prophylaxis, asymptomatic carriers of this organism were examined by high-resolution computed tomography and PCR every 2 weeks. RA patients who had developed PCP received PCR tests every week. Once negative results were obtained, PCR testing was scheduled at Months 1, 3, and 6, followed by reexaminations every 6 months. RESULTS: We found 9 cases of asymptomatic carriage of P. jiroveci. All the carriers had received low doses of methotrexate. Upon introduction of PCP prophylaxis, 5 cases tested negative for PCR within 1 month. Three carriers developed PCP before starting prophylaxis, but these tested negative for PCR after short periods (1-2 weeks) of PCP treatment. Once P. jiroveci was eradicated, all cases maintained negative PCR results during followup without prophylactic intervention, even after resuming immunosuppressive therapy. One patient refused PCP prophylaxis, but no PCP developed. CONCLUSION: RA patients with asymptomatic carriage of P. jiroveci benefited from short-term prophylaxis against PCP. Positive PCR results appeared to be predictive of future development of PCP in RA patients. Identification of P. jiroveci carriers will encourage prompt introduction of PCP prophylaxis when rheumatologists consider immunosuppressive therapy for RA.
19191187 Combination treatment with leflunomide and methotrexate for patients with active rheumatoi 2009 Jan OBJECTIVE: To determine the efficacy and safety of the combination of leflunomide and methotrexate for the treatment of patients with active rheumatoid arthritis (RA) in an open, non-comparative, multicentre trial. METHODS: Seventy-four patients with active RA were enrolled to receive concomitantly leflunomide (no loading dose, 10 mg/day) and methotrexate (starting at 7.5 mg/week and titrating up to 15 mg/week) for 20 weeks. The primary end-point was a 20% improvement in the American College of Rheumatology (ACR) criteria at 20 weeks. Safety measures included evaluation of adverse events at each visit and laboratory data, including haematology and liver function tests. Intention-to-treat analyses were conducted. RESULTS: Sixty-five patients completed 20 weeks of treatment, and 71.6% were responders based on the ACR20 criteria. After 20 weeks, the mean changes were -16.3 for tender joint count, -12.0 for swollen joint count, -44.0 for physician global assessment, -34.3 for patient global assessment, -22.7 for erythrocyte sedimentation rate, and -0.65 for the Health Assessment Questionnaire score. Adverse events occurred in 40.5% of the patients, and were considered serious in four patients who discontinued therapy. Abnormal liver function was noted for 16 patients (21.6%). Two of these patients were withdrawn from the study; after discontinuing the medication, their liver function recovered fully. CONCLUSION: THE combination of leflunomide and methotrexate was effective and well tolerated in the treatment of active RA patients. This combination may be a useful option as an initial treatment for active RA before starting biological agents.
19285366 [Cutaneous leishmaniasis in rheumatoid arthritis]. 2009 Jul INTRODUCTION: Cutaneous leishmaniasis is a protozoal infection. Its prevalence is increasing, especially in immunocompromised subjects. CASE REPORTS: We report four patients with rheumatoid arthritis, treated with methotrexate and prednisone who developed cutaneous leishmaniasis. Clinical outcome was favorable after institution of antimony therapy in three cases despite the continuation of methotrexate and prednisone. One patient failed to respond to therapy. DISCUSSION: The frequency of cutaneous leishmaniasis is increasing especially in immunocompromised subjects. In our patients, rheumatoid arthritis, corticosteroid therapy and methotrexate were predisposing factors of cutaneous leishmaniasis.
20235210 Predictors for remission in rheumatoid arthritis patients: A systematic review. 2010 Aug OBJECTIVE: To summarize the potential predictors of remission in patients with rheumatoid arthritis (RA). METHODS: We performed a systematic review of prognostic studies that identified the predictors of remission in RA patients. Studies were identified in Medline, EMBase, and the Cochrane Registry, and by hand search. We included only studies performing multivariate analysis. RESULTS: A total of 18 studies from 2,062 citations were included. The following variables were found to be the independent predictors of RA remission: male sex; young age; late-onset RA; short disease duration; nonsmoker; low baseline disease activity; mild functional impairment; low baseline radiographic damage; absence of rheumatoid factor and anti-citrullinated peptide; low serum level of acute-phase reactant, interleukin-2, and RANKL at baseline; MTHFR 677T alleles and 1298C alleles in the methotrexate (MTX)-treated patients; magnetization transfer ratio 2756A allele +/- either the SLC 19A180A allele or the TYMS 3R-del6 haplotype in the MTX plus sulfasalazine combination-treated patients; early treatment with nonbiologic disease-modifying antirheumatic drug (DMARD) combinations; the use of anti-tumor necrosis factor (anti-TNF); the concurrent use of DMARDs in anti-TNF-treated patients; and moderate or good response to treatments at the first 6 months. The magnitude of the association in the individual predictor was diverse among the studies depending on the patient characteristics, the study characteristics, and the variables used to adjust for in the models. CONCLUSION: A number of independent predictors of remission, i.e., baseline clinical and laboratory characteristics and genetic markers, were summarized. The predictive value of prognostic factors recently identified needs to be confirmed.