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ID PMID Title PublicationDate abstract
21909699 Inhibition of MAP kinase in synovium by treatment with tocilizumab in rheumatoid arthritis 2011 Nov To investigate the histological changes of mitogen-activated protein kinase (MAPK) in synovium with tocilizumab in rheumatoid arthritis (RA), synovial tissue samples were assessed from ten methotrexate (MTX)-treated RA patients for control and ten tocilizumab with MTX-treated RA patients. The synovium was observed using hematoxylin and eosin (H&E) stain and analyzed immunohistochemically for the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), CD4 (T cell), CD20 (B cell), CD68 (macrophage), vascular endothelial growth factor (VEGF), CD29 (β-1 integrin), phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK [extracellular signal-regulated kinase (ERK) 1/ERK2], and phospho-c-Jun N-terminal kinase (JNK). H&E staining showed that there is a significant difference of cell proliferation; however, there is no change of hypervascularity in the synovium between both groups. An immunohistochemical examination showed that the decrease of CD29 (β-1 integrin) and JNK was found significant, while ERK was increased in the tocilizumab group. CD20, B-lymphocyte, was decreased in the tocilizumab group compared with the MTX group significantly. IL-6 was completely blocked in the patients who received tocilizumab. TNF-α was similarly expressed in the interstitial cells of synovium of patients in both groups. MMP-3 and CD68 were similarly expressed on the surface of synovium. VEGF was less expressed in both groups. These findings indicate that the inhibition of CD20, CD29, and JNK in MAPK may be involved in the efficacy of tocilizumab compared with MTX treatment in RA.
22825547 Epstein-Barr virus and methotrexate-related CNS lymphoma in a patient with rheumatoid arth 2013 Jul Patients with rheumatoid arthritis (RA), especially those treated with methotrexate (MTX), might have an increased risk of lymphoproliferative disorders that are associated with Epstein-Barr virus (EBV). We describe a case of EBV-associated central nervous system (CNS) lymphoma (diffuse large B-cell lymphoma) in a patient with RA on a short course of MTX treatment. The neoplastic cells express the B-cell surface markers (CD20, Pax-5 and CD30), and EBV-encoded RNA was demonstrated by in situ hybridization. The patient's lymphoma did not recur for the 8-year follow-up period after the tumor resection and cessation of MTX. MTX may promote EBV-positive CNS lymphoma in RA patient due to its immunosuppressive properties as well as reactivating latent EBV infection.
23078058 The status of fostamatinib in the treatment of rheumatoid arthritis. 2012 Sep Fostamatinib (R788) is a prodrug rapidly converted to its active metabolite on oral administration. This (known as R406) is a potent inhibitor of spleen tyrosine kinase, required for the expression of a number of proinflammatory cytokines. Fostamatinib has shown significantly superior efficacy (when compared with placebo) in the control of patients with rheumatoid arthritis not responding to methotrexate in Phase II clinical trials. Treatment emergent adverse events with a higher frequency than in those on placebo included diarrhea, hypertension, urinary tract infections, neutropenia and elevated transaminases. The studied doses have shown a linear pharmacokinetic pattern and the administration of methotrexate does not affect it. Fostamatinib may have a role in the therapy of patients with rheumatoid arthritis with poor response to conventional therapy. If these results are confirmed once Phase III studies are completed, it may find a place in the evolving treatment algorithm for rheumatoid arthritis.
22018183 The COBRA trial 20 years later. 2011 Sep This article provides a perspective on the immediate and follow-up results of the COBRA trial that compared the combination of step-down prednisolone, methotrexate and sulfasalazine with sulfasalazine monotherapy in early rheumatoid arthritis (RA). The combination provided immediate relief of symptoms and signs of RA, but the clinical benefit compared to monotherapy appeared mostly dependent on low-dose glucocorticoid therapy that was mandatorily discontinued after 28 weeks. Strong benefit was apparent in the slowing of joint damage progression, and this effect persisted for over 10 years despite uncontrolled therapy after the trial period. In the trial toxicity of COBRA was less than monotherapy, and long-term safety of the regimen was comparable to regimens that do not include glucocorticoids. COBRA was the first study to validate the 'reverse-pyramid' concept in RA, and helped to establish the idea of a window of opportunity where the prognosis of RA may be altered with early and intensive therapy. Subsequent studies have shown COBRA is feasible in practice, acceptable to patients, and has efficacy similar to the combination of TNF inhibition and high-dose methotrexate, at a fraction of the cost.
21246373 Insulin-like growth factor I receptor density on CD4+T-lymphocytes from active early stero 2012 Feb The IGF-IR density on CD4+T-lymphocytes was studied using flow cytometry in 40 early steroid- and DMARD-naïve rheumatoid arthritis (RA) patients before and after 52 weeks of treatment with methotrexate+placebo or methotrexate+cyclosporine A and in 15 controls. RA patients had increased IGF-IR density on CD4+T-lymphocytes at week 0 and week 52, irrespective of treatment. IGF-IR-positive CD4+T-lymphocytes fraction decreased during treatment, but neither at week 0 nor at week 52 did it differ from healthy controls. No correlations were found to disease activity parameters.
21971942 Prognosis of pneumocystis pneumonia complicated in patients with rheumatoid arthritis (RA) 2012 Aug Clinical presentation of pneumocystis pneumonia (PCP) during immunosuppressive therapy for rheumatic diseases was compared between patients with rheumatoid arthritis (RA; n = 7) and those without RA (non-RA; n = 12) based on a chart review. Both RA and non-RA patients with PCP were treated with methotrexate (n = 7) combined with steroids (n = 6) and/or biologics (n = 4). RA-PCP patients were found to have a higher mortality rate than non-RA-PCP patients (3/7 vs. 0/12, respectively; p = 0.036) due to a later exacerbation of interstitial pneumonia and a higher presentation rate of diffuse pulmonary lesions (4/7 vs. 1/12, respectively; p = 0.036) despite lower mean levels of serum beta-D: -glucan (314 ± 214 vs. 1139 ± 1114 pg/ml, respectively; p = 0.02) that suggested a lower burden of Pneumocystis jirovecii. In conclusion, PCP in RA patients with existing pulmonary lesions may trigger subsequent progression to lethal interstitial pneumonia.
23196701 Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to m 2013 Dec OBJECTIVE: To compare EuroQol 5-Dimensions (EQ-5D) utility and quality-adjusted life-years (QALYs) in patients with early, methotrexate (MTX) refractory rheumatoid arthritis (RA), randomised to addition of infliximab (IFX) or sulfasalazine and hydroxychloroquine (SSZ+HCQ). METHODS: RA-patients with symptoms <1 year were enrolled between 2002 and 2005 at 15 Swedish centres. After 3-4 months of MTX monotherapy, patients with a remaining DAS28>3.2 were randomised to addition of IFX or SSZ+HCQ and followed for 21 months. EQ-5D profiles were collected every 3 months. Between-group comparisons of utility change and accumulated QALYs were performed, using last observation carried forward (LOCF) following protocol breach. Missing data were imputed by linear interpolation or LOCF. Sensitivity analyses applying baseline observation carried forward (BOCF) or restricted to completers were conducted. RESULTS: Of 487 patients initially enrolled, 128 and 130 were randomised to IFX or SSZ+HCQ, respectively. Mean utility in the IFX and SSZ+HCQ groups increased from 0.52 (SD 0.27) and 0.55 (SD 0.27) at randomisation to 0.66 (SD 0.25) and 0.63 (SD 0.27) at 21 months (adjusted mean difference favouring IFX 0.04; 95% CI -0.01, 0.09; p=0.15). Average accumulated QALYs were 1.10 (SD 0.37) and 1.07 (SD 0.42) in the IFX and SSZ+HCQ groups, respectively (adjusted mean difference favouring IFX 0.07; 95%CI -0.01, 0.14; p=0.07). BOCF analysis showed similar results, while differences were reversed, though remained statistically non-significant among completers. Dropout rates in the IFX/SSZ+HCQ groups were 30%/43% (p=0.01). CONCLUSIONS: Comparing addition of IFX or SSZ+HCQ to MTX in active early RA, no statistically significant differences in utility or QALY gain could be detected over 21 months. TRIAL REGISTRATION: Registered in WHO database at the Karolinska University Hospital, number CT20080004.
23053688 A multicenter, randomized, double-blind clinical trial of combination therapy with Anbainu 2013 Jan This study aims to evaluate the clinical and radiological efficacy as well as safety profiles of Anbainuo, a recombinant human TNFRII:Fc fusion protein, combined with methotrexate (MTX) versus MTX alone or Anbainuo alone in the treatment of Chinese patients with moderate to severe rheumatoid arthritis (RA). In this 24-week, multicenter, double-blind, active comparator-controlled study, 396 RA patients were randomized into combination therapy group (Anbainuo plus MTX), Anbainuo group, or MTX group. Clinical response was assessed using the American College of Rheumatology (ACR)-N, ACR20, ACR50, ACR70, and van der Heijde modification of Sharp score, among which ACR-N and ACR20 were defined as primary major endpoints. After 24 weeks of treatment, the ACR-N in the combination therapy group (12.79 ± 9.24 %) was significantly higher than that in Anbainuo group (9.56 ± 11.16 %) and in MTX group (5.08 ± 11.1 %) (p = 0.00 and p = 0.00, respectively). Patients in Anbainuo group had significantly higher ACR-N than those in MTX group (p = 0.02). More patients in the combination therapy group (53.6 %) achieved ACR50 improvement response than those in the MTX group (30.8 %). ACR70 of combination therapy group (27.7 %) was significantly higher than that of Anbainuo group (15.8 %) and MTX group (7.70 %), with no significant difference between Anbainuo group and MTX group. DAS28-ESR in the combination therapy group was significantly reduced compared to either monotherapy groups. Moreover, DAS28-ESR was significantly lower in Anbainou group than in MTX group. The combination therapy group also showed significantly less radiographic progression than the MTX group (p = 0.03). The total adverse events (AE) in the combination group (40.9 %) was significantly higher than those in the MTX group (28.8 %) (p < 0.05). Anbainuo combined with MTX therapy can effectively control the disease activity and radiographic progression of RA, while the incidence of AE also increased compared to either Anbainuo or MTX.
22152098 A short-chain methotrexate polyglutamate as outcome parameter in rheumatoid arthritis pati 2012 Mar OBJECTIVES: Methotrexate (MTX) is a cornerstone in the treatment of rheumatoid arthritis (RA). Although in general MTX is very effective, the major drawback is the large inter-patient variability in clinical response. The circulating levels of MTX polyglutamates (MTXPGs) are supposed to correlate with clinical efficacy, therefore having a potential role in drug monitoring. However, there is a controversial discussion about the importance of methotrexate polyglutamates as outcome parameters in the therapy of rheumatoid arthritis. The aim of the present study was to investigate the formation and pharmacokinetics of MTXPGs and to correlate their concentration with clinical response in MTX-naïve patients. METHODS: The pharmacokinetics of erythrocyte MTXPGs was determined in samples of nineteen MTX-naïve patients by high pressure liquid chromatography (HPLC) using post-column photo-oxidation and fluorimetric detection. The relationship between erythrocyte concentrations of MTXPGs and the primary outcome parameter DAS-28 was assessed using the Spearman's correlation coefficient. RESULTS: The short-chain polyglutamate MTXPG2 revealed to be a potential marker for clinical outcome in rheumatoid arthritis with a statistically significant positive correlation of MTXPG2 Cmax levels and improvement in DAS-28 (+0.518, p=0.023) over 16 weeks. Furthermore, Cmax levels of MTXPG2 negatively correlated with basophils (-0.478, p=0.038) and eosinophils (-0.531, p=0.019), both pro-inflammatory cells involved in the disease. CONCLUSIONS: MTXPG2 seems to be a potential indicator for clinical response and may serve as a marker for drug monitoring.
22972168 A study on the selection of DMARDs for the combination therapy with adalimumab. 2012 Jun 27 We evaluated whether or not the effect of adalimumab (ADA) in combination with the disease-modifying antirheumatic drugs (DMARDs) other than methotrexate (MTX) is comparable to the ADA+MTX therapy for the treatment of rheumatoid arthritis (RA). A total of 216 patients with active RA at Kohnan Kakogawa Hospital and Kobe University Hospital were enrolled. Clinical and functional outcomes were compared among 4 groups, ADA alone (A group), ADA + MTX (B group), ADA + MTX + other DMARDs (C group), and ADA + other DMARDs (D group), and the retention rates of ADA were evaluated with or without MTX. CRP was significantly decreased from initial measurement at 1 month in all 4 groups, but the continuous efficacy with the statistical significance at all measurement points were observed only in combination with MTX (P<0.05), which was reflected by significantly higher retention rates. Similarly, the disease activities were improved, and particularly the remission rates (DAS28-CRP < 2.3) of A, B and C groups (>42.9%) were higher than that of D group (29.4%) at 2 year. An index of patients' basic activities of daily living, M-HAQ score of A, B and C groups was also better than that of D group. While, looking at the mean changes of M-HAQ from the baseline at 2 years, potential effect of other DMARDs on M-HAQ was also suggested. The results show that ADA + MTX therapy is significantly superior than ADA + other DMARDs in ameliorating RA.
22393641 [Seroprevalence of HBsAgs in patients with rheumatoid arthiritis in a hospital setting in 2011 Dec PURPOSE: Rheumatoid arthritis is the most common chronic inflammatory joint disease in adults. In Senegal, where biotherapy is unavailable, treatment of RA relies on a combination of glucocorticoids and disease-modifying antirheumatic drugs (DMARD). Since DMARD, particularly methotrexate, induce hepatotoxicity pretreatment assays of serum transaminase and albumin levels, as well as serological tests for the hepatitis B and C viruses is recommended. Hepatitis B virus (HBV) infection is endemic in Africa, particularly in Senegal. The purpose of this study was to assess the seroprevalence of the HBV surface antigen (HBsAg) for HBV in 258 patients with RA in Senegal as a basis for defining the least hepatotoxic DMARD for these patients and ensuring the most suitable monitoring. METHOD: This retrospective study was based on a review of the medical records of patients examined between January 2005 and December 2009 at the rheumatology outpatient clinic of the Aristide Le Dantec Teaching Hospital in Dakar, Senegal. All patients met the American College of Rheumatology criteria for RA. RESULTS: A total of 258 patients were tested for HBsAg. Tests were positive in 6 for a seroprevalence of 2.3%. All 6 positive patients were women with a mean age of 48.7 years (range, 16-79 years). Transaminase levels were normal in 5 patients. In the remaining patient, ASAT level elevation were twice normal and ALAT was normal. No patients had clinical evidence of liver disease. CONCLUSION: HBsAg seroprevalence in our population of patients with RA was lower than in the general population of Senegal: 2.3% versus 15%-18%. No evidence indicated that HBVinfection produced specific features in patients with RA. Based on these findings, widespread use of methotrexate in optimal dosages appears safe in patients with RA in Senegal. Treatment should be accompanied by careful attention to HBV prevention.
22083220 Cardiovascular safety of biologic therapies for the treatment of RA. 2011 Nov 15 Cardiovascular disease represents a major source of extra-articular comorbidity in patients with rheumatoid arthritis (RA). A combination of traditional cardiovascular risk factors and RA-related factors accounts for the excess risk in RA. Among RA-related factors, chronic systemic inflammation has been implicated in the pathogenesis and progression of atherosclerosis. A growing body of evidence--mainly derived from observational databases and registries--suggests that specific RA therapies, including methotrexate and anti-TNF biologic agents, can reduce the risk of future cardiovascular events in patients with RA. The cardiovascular profile of other biologic therapies for the treatment of RA has not been adequately studied, including of investigational drugs that improve systemic inflammation but alter traditional cardiovascular risk factors. In the absence of large clinical trials adequately powered to detect differences in cardiovascular events between biologic drugs in RA, deriving firm conclusions on cardiovascular safety is challenging. Nevertheless, observational research using large registries has emerged as a promising approach to study the cardiovascular risk of emerging RA biologic therapies.
21209239 Fostamatinib, a Syk-kinase inhibitor, does not affect methotrexate pharmacokinetics in pat 2011 Sep Fostamatinib (R788) is being investigated as an add-on therapy for the treatment of rheumatoid arthritis (RA) in patients with inadequate response to methotrexate (MTX). This study evaluated the potential pharmacokinetic interaction between R788 and MTX. Sixteen RA subjects on a stable weekly MTX regimen were enrolled and received MTX on days 1 and 8. Twelve subjects received 100 mg of R788 orally, and 4 subjects received a matching placebo twice daily from days 4 to 8 and once daily on days 3 and 9. Blood samples were collected on days 1 and 8 for MTX and 7-hydroxymethotrexate (7-OH-MTX), and days 3 and 9 for R788 and its active metabolite, R406. MTX and 7-OH-MTX pharmacokinetic parameters were similar on days 1 and 8. In the R788 group, the mean day 8 to day 1 ratios (90% confidence intervals) of maximum concentration and area under the plasma concentration-time curve estimates were 1.01 (0.85-1.20) and 1.12 (0.90-1.40) for MTX and 1.06 (0.82-1.35) and 1.06 (0.83-1.36) for 7-OH-MTX, respectively. Urinary excretion of MTX and 7-OH-MTX was also similar with or without R788, averaging 58% to 69% and 4% to 5% of the MTX dose, respectively. The data suggest that there is no clinically significant pharmacokinetic interaction of R788 and MTX in RA patients.
22178253 [Can the medication in patients with rheumatoidarthritis in remission be stopped?]. 2012 Jan Rheumatoid arthritis is a chronic systemic inflammatory disease that causes significant morbidity and mortality. The combined use of methotrexate and biological agents directed against tumor necrosis factor (TNF) has achieved significant improvement in clinical, radiographic and functional parameters not seen previously and has revolutionized the therapeutic goal of achieving remission in clinical, structural and functional parameters. The next goal should be to achieve remission without the use of biological drugs and later without medication. Although there is evidence about the efficacy and safety of TNF inhibitors, there is none on remission without the use of biological agents or disease modifying drugs.
23148635 Genetic variation in the SLC19A1 gene and methotrexate toxicity in rheumatoid arthritis pa 2012 Nov AIM: We investigated the clinical relevance of SLC19A1 genetic variability for methotrexate (MTX) toxicity in rheumatoid arthritis patients using a haplotype-based approach. PATIENTS & METHODS: Two hundred and twelve unrelated rheumatoid arthritis patients and 89 lymphoblastoid cell lines were used to investigate the effect of SLC19A1 SNPs and haplotypes on MTX adverse events and treatment discontinuation. RESULTS: Two putatively functional SNPs in high linkage disequilibrium, rs1051266 and rs1131596, were associated with protection (hazard ratio: 0.33; 95% CI: 0.16-0.69; adjusted p = 0.021 and hazard ratio: 0.38; 95% CI: 0.17-0.27; adjusted p = 0.021, respectively) of discontinuation of MTX treatment owing to toxicity. These SNPs were also associated with protection from infections. SLC19A1 haplotype analysis found significant associations with MTX discontinuation owing to toxicity (p = 0.025). Quantification of SLC19A1 mRNA in cell lines suggested that rs1131596 was not a major causal variant. CONCLUSION: Individual SNP and haplotype analyses suggest that rs1051266 could be a functional variant altering MTX toxicity; however, validation in independent studies is needed.
21352592 Adalimumab reduces hand bone loss in rheumatoid arthritis independent of clinical response 2011 Feb 27 BACKGROUND: Anti-TNF therapy has been shown to reduce radiographic joint damage in rheumatoid arthritis (RA) independent of clinical response. This has previously not been examined for periarticular bone loss, the other characteristic feature of bone involvement in RA.The objective of this study was to examine if treatment with the TNF-α inhibitor adalimumab also could reduce periarticular bone loss in RA patients independent of disease activity. METHODS: RA patients were recruited from the PREMIER study and included 214 patients treated with methotrexate (MTX) plus adalimumab and 188 patients treated with MTX monotherapy. Periarticular bone loss was assessed by digital X-ray radiogrammetry metacarpal cortical index (DXR-MCI). Change in DXR-MCI was evaluated in patients with different levels of clinical response, as assessed by changes in DAS28 score at 52 weeks and in mean C-reactive protein (CRP) levels during follow-up. RESULTS: In the MTX group, there was a greater median DXR-MCI loss among patients with moderate and high disease activity compared to those in remission or with low disease activity (-3.3% vs. -2.2%, p = 0.01). In contrast, periarticular bone loss was independent of disease activity (-1.9% vs. -2.4%, p = 0.99) in the combination group. In the MTX group patients with a mean CRP of ≥ 10 mg/l lost significantly more DXR-MCI than patients with low CRP (-3.1% vs. -1.9%, p <0.01) whereas in the combination group no significant differences between the two CRP groups was seen (-2.4% vs. -2.0%, p = 0.48). CONCLUSION: Adalimumab in combination with MTX reduces periarticular bone loss independently of clinical response. These results support the hypothesis that TNF-α stimulates the osteoclast not only by the inflammatory pathway but do also have a direct effect on the osteoclast. TRIAL REGISTRATION: ClinicalTrials (NCT): NCT001195663.
21829083 [B-cell lymphoma possessing t(14;18)(q32;q21)in a patient with rheumatoid arthritis receiv 2011 Aug There is evidence of a slight increase in malignant lymphoma among rheumatoid arthritis(RA)patients receiving methotrexate( MTX). Increased rates of lymphoma have been attributed to reactivation of the Epstein-Barr virus(EBV). A 72-yearold woman was admitted to our hospital for generalized lymph adenopathy. She suffered from RA and has been treated with MTX for 7 years; the total amount of MTX received was around 2, 700 mg. The cervical lymph node revealed a diffuse proliferation of large atypical lymphocytes. An immunophenotype revealed CD10+, CD19+, CD20+, and k+. The chromosome analysis showed a complex abnormality containing t(14;18)(q32;q21). The tumor cells were positive for EBV sequences by in situ hybridization(ISH). A rituximab containing regimen was effective, but a systemic relapse occurred 4 years later. The biopsied sample was diagnosed as diffuse large B-cell lymphoma. FISH analysis revealed positive for t(14;18)(q32;q21), however, EBV was negative using ISH. In general, the concurrence of t(14;18)(q32;q21)and EBV in the B-cell lymphoma is rare. In addition, the negative change in EBV in the relapsed lymphoma cells revealed a quite rare phenomenon.
22212411 Immunohistological analysis of synovium treated with abatacept in rheumatoid arthritis. 2013 Jul The aim of this study was to investigate the histological changes following the treatment with abatacept compared with methotrexate (MTX) by an immunohistological examination of synovial tissue for eleven different molecules to detect the expression patterns of cytokines. We histologically assessed the synovial tissues from 10 methotrexate (MTX)-treated RA patients as controls and 5 abatacept plus MTX-treated RA patients. The synovium samples from both group were assessed by hematoxylin and eosin (HE) staining and analyzed for their expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), CD20, CD68, vascular endothelial growth factor (VEGF), CD4, CD8, CD28, CD80, and CD86 by an immunohistological examination. HE staining showed that there was a decrease in cell proliferation in the synovium of the RA patients who received abatacept compared with the controls. TNF-α, IL-6, and VEGF were not significantly different in either of the groups. On the other hand, MMP-3, CD68, CD4, CD8, CD20, CD80, and CD86 were significantly decreased in the abatacept group compared with the control (P < 0.05). Based on the histological analysis of the synovium, it appears that the efficacy of the treatment with abatacept may involve the inhibition of cell proliferation, with decreases in the expression of MMP-3, CD68, CD4, CD8, CD20, CD80, and CD86 in the synovium. These findings indicate inhibition of not only T cells but also B cells and macrophages, which likely plays a role in the efficacy of abatacept in RA patients.
22353705 Leflunomide in monotherapy of rheumatoid arthritis: meta-analysis of randomized trials. 2012 INTRODUCTION: Rheumatoid arthritis (RA) is a chronic systemic disease of the connective tissue that leads to progressive joint destruction, disability, withdrawal from occupational activity, and premature death. OBJECTIVES: The aim of the paper was to evaluate the efficacy and safety of leflunomide compared with placebo, methotrexate, and sulfasalazine in monotherapy of RA. PATIENTS AND METHODS: A systematic search of databases (MEDLINE, EMBASE, Cochrane CENTRAL) was performed. Only randomized blind trials were included into the analysis. The quality of the trials was assessed by the Jadad scale. A quantitative synthesis of the results was performed (meta-analysis). RESULTS: The analysis included 7 trials involving 2861 patients (1432 on leflunomide, 312 on placebo, 922 on methotrexate, and 133 on sulfasalazine). Leflunomide, compared with placebo, increased the probability of the American College of Rheumatology 20% improvement (ACR20) response 2-fold (relative risk [RR], 2.02; 95% CI, 1.46-2.80) and the probability of ACR50 response 4-fold (RR, 4.36; 95% CI, 2.33-8.17), after 1 year of treatment. Efficacy of leflunomide did not differ from that of methotrexate with reference to the majority of endpoints. Leflunomide showed partial superiority over methotrexate in the percentage of patients obtaining ACR50 and ACR70 response, doctor's assessment of the disease activity, reduction in C-reactive protein (CRP) levels, and improvement of the quality of life (assessed with the modified health assessment questionnaire [HAQ]). Sulfasalazine showed partial superiority in the reduction of erythrocyte sedimentation rate, while leflunomide was superior to sulfasalazine the ACR20 and ACR50 clinical response, quality of life (assessed with the HAQ), doctor's and patient's assessment of the disease activity, and reduction in CRP levels. CONCLUSIONS: There were no significant differences between the effects of treatment with leflunomide and methotrexate or sulfasalazine, but leflunomide monotherapy proved more effective than placebo in relieving symptoms and signs of RA.
22134750 Response to traditional disease-modifying anti-rheumatic drugs in indigent South Africans 2012 Apr The clinical response to traditional disease-modifying anti-rheumatic drugs (DMARDs) in indigent South Africans with early rheumatoid arthritis was investigated. A cohort of patients with early (≤2 years) RA who were DMARD-naïve at inception were prospectively assessed for response to DMARDs using the Simplified Disease Activity Index (SDAI) over a 12-month period. Patients with low disease activity (LDA) at 12 months were compared to those with moderate and high disease activity with respect to demographic, clinical, autoantibody and radiographic features. The 171 patients (140 females) had a mean (SD) age of 47.1 (12.4) years, symptom duration of 11.7 (7.1) months and baseline SDAI of 39.4 (16.2). There was a significant overall improvement in the SDAI and its components in the 134 (78.4%) patients who completed the 12 months visit, but only 28.4% of them achieved LDA. The majority of patients (91%) were treated with methotrexate as monotherapy or in combination with chloroquine and/or sulphasalazine. Baseline features that independently predicted a LDA state at 12 months were lower Health Assessment Questionnaire Disability Index (p = 0.023) and a higher haemoglobin level (p = 0.048). Receiver operating characteristic curve analysis showed that the 6-month SDAI was better than the baseline SDAI in predicting the 12-month SDAI (area under the curve of 0.69 vs. 0.52, respectively, p = 0.008). In conclusion, less than a third of the patients achieved a low disease activity at 12 months on traditional DMARDs. Patients who have an inadequate response to traditional DMARDs at 6 months are unlikely to show further improvement on traditional DMARDs at 12 months. These findings underscore the need for better disease control by an aggressive tight control strategy, including intense patient education and biologic therapy.