Methotrexate reduces inflammatory cell numbers, expression of monokines and of adhesion molecules in synovial tissue of patients with rheumatoid arthritis

Dolhain, Radboud J E M; Tak, Paul P.; Dijkmans, Ben A. C.; Kuiper, Patricia; Breedveld, Ferdinand C.; Miltenburg, A. M. M.

doi:10.1093/rheumatology/37.5.502

Cited by 127 publications

(94 citation statements)

References 2 publications

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“…The specific effect of leflunomide and methotrexate on the number of macrophages and T cells in synovial tissue samples was more pronounced at 4 months, and there was also a marked effect of both compounds on the expression of adhesion molecules, a finding consistent with previous observations after methotrexate treatment (43). These changes were even more noticeable in the patients who fulfilled the ACR 20% response criteria.…”

Section: Discussionsupporting

confidence: 88%

“…This appears to be especially beneficial for the evaluation of novel specific therapies such as TNF␣ blockade (40,41), and anti-CD4 monoclonal antibodies (32). For treatment with conventional DMARDs and biologics with diverse effects (42), the changes might be more diffuse and do not necessarily represent a specific effect (43)(44)(45)(46). In this study, we observed, in general, a similar response after 4 months of treatment with either leflunomide or methotrexate.…”

Section: Discussionsupporting

confidence: 52%

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Modulation of inflammation and metalloproteinase expression in synovial tissue by leflunomide and methotrexate in patients with active rheumatoid arthritis: Findings in a prospective, randomized, double-blind, parallel-design clinical trial in thirty-nine patients at two centers

Kraan

Reece

Barg

et al. 2000

Arthritis & Rheumatism

152

101

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Objective. Leflunomide and methotrexate have proven to be efficacious in reducing joint inflammation and slowing destruction in clinical trials of patients with rheumatoid arthritis (RA). This study was conducted to provide more insight into the mechanism of action of these agents in synovial tissue.Methods. In a 2-center, prospective, randomized, double-blind clinical trial, we compared leflunomide (20 mg/day, after a 3-day 100 mg/day loading dose) and methotrexate ( Conclusion. Leflunomide and methotrexate are clinically efficacious drugs that interfere with mechanisms involved in joint inflammation and destruction of joint integrity.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 52%

Modulation of inflammation and metalloproteinase expression in synovial tissue by leflunomide and methotrexate in patients with active rheumatoid arthritis: Findings in a prospective, randomized, double-blind, parallel-design clinical trial in thirty-nine patients at two centers

Kraan

Reece

Barg

et al. 2000

Arthritis & Rheumatism

152

101

View full text Add to dashboard Cite

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“…However, the current study is limited in its capacity to evaluate the complete implication of DCs in the pathogenesis of RA: the small number of patients, variability in patient's factors at study entry (disease duration, previous DMARD treatment [46,47]). It has to be continued in order to allow statistical correlations and to prove the importance of adhesion and co-stimulatory molecules expression on DCs as targets for future immunotherapies.…”

Section: Discussionmentioning

confidence: 99%

Co‐stimulatory and adhesion molecules of dendritic cells in rheumatoid arthritis

Bălănescu

Radu

Nat

et al. 2002

J Cellular Molecular Medi

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Dendritic cells (DCs) in the rheumatoid arthritis (RA) joint mediate the immunopathological process and act as a potent antigen presenting cell. We compared the expression of co‐stimulatory and adhesion molecules on DCs in RA patients versus controls with traumatic joint lesions and evalulated the correlation between the immunophenotypical presentation of DCs and the clinical status of the disease. Samples of peripheral venous blood, synovial fluid (SF) and synovial tissue (ST) were obtained from 10 patients with RA at the time of hip or knee replacement and from 9 control patients with knee arthroscopy for traumatic lesions. Clinical status was appreciated using the DAS28 score. Blood, SF and dissociated ST cell populations were separated by centrifugation and analyzed by flow cytometry. Cells phenotypes were identified using three‐color flow cytometry analysis for the following receptors HLA‐DR, CD80, CD83, CD86, CD11c, CD18, CD54, CD58, CD3, CD4, CD8, CD19, CD20, CD14, CD16, CD56. HLA‐DR molecules, co‐stimulatory receptors CD80, CD86, CD83 and adhesion molecules CD18, CD11c, CD54, CD58, were analyzed by two‐color immunofluorescence microscopy on ST serial sections. In patients with active RA (DAS28>5.1) we found a highly differentiated subpopulation of DCs in the ST and SF that expressed an activated phenotype (HLA‐DR, CD86+, CD80+, CD83+, CD11c+, CD54+, CD58+). No differences were found between circulating DCs from RA patients and control patients. Our data suggest an interrelationship between clinical outcome and the immunophenotypical presentation of DCs. Clinical active RA (DAS28>5.1) is associated with high incidence of activated DCs population in the ST and SF as demonstrated by expression of adhesion and co‐stimulatory molecules.

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“…Despite renal clearance of MTX, the reduction in renal function associated with CSA use did not result in serious MTX toxicity. CSA also inhibits T cell function and interleukin-2 production (33), and MTX acts on macrophages (34). CSA has been demonstrated to delay radiologic damage (35)(36)(37) and is effective in both early (38) and established RA, as well as in combination with MTX in partial responders to MTX (13,14).…”

Section: Discussionmentioning

confidence: 99%

Treatment of poor-prognosis early rheumatoid arthritis: A randomized study of treatment with methotrexate, cyclosporin A, and intraarticular corticosteroids compared with sulfasalazine alone

Proudman

Conaghan

Richardson

et al. 2000

Arthritis & Rheumatism

113

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Objective. To determine whether a regimen of methotrexate, cyclosporin A, and corticosteroids introduced at onset in poor-prognosis rheumatoid arthritis (RA) can produce a significant improvement in outcome compared with standard monotherapy with sulfasalazine (SSZ).Methods. Eighty-two consecutive patients presenting with new, untreated RA of less than 12 months' duration who fulfilled criteria for poor long-term outcome were randomized to receive either combination therapy (n ‫؍‬ 40) or SSZ alone (n ‫؍‬ 42). The primary outcome measures were remission and American College of Rheumatology (ACR) criteria for 20% improvement at 48 weeks.Results. After 48 weeks, the numbers of patients who met the ACR criteria for 20% improvement were not significantly different between the two groups (combination 58% versus SSZ 45%), and similar numbers of patients had persisting clinical remission (ϳ10% both groups). During the first 3 months, there were significantly greater reductions in parameters of disease activity in the combination group. By 24 weeks, the swollen and tender joint counts, C-reactive protein levels, and erythrocyte sedimentation rates had fallen significantly in both groups, with a greater improvement in the swollen and tender joint count in the combination group. At 48 weeks, the radiographic damage score had increased by a median of 1 (range 0-42.5) in the combination group and 1.25 (range 0-72.5) in the SSZ group (P ‫؍‬ 0.28; although there were significant differences in the scores for the right hand). There were significantly fewer withdrawals due to lack of efficacy in the combination group than in the SSZ group (1 of 40 versus 10 of 42; P ‫؍‬ 0.007). In the combination group, dose reduction was needed in 22.5% because of hypertension and in 22.5% because of elevated creatinine levels. Over 48 weeks, serum creatinine increased in both groups, but particularly in the combination arm.

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Methotrexate reduces inflammatory cell numbers, expression of monokines and of adhesion molecules in synovial tissue of patients with rheumatoid arthritis

Cited by 127 publications

References 2 publications

Modulation of inflammation and metalloproteinase expression in synovial tissue by leflunomide and methotrexate in patients with active rheumatoid arthritis: Findings in a prospective, randomized, double-blind, parallel-design clinical trial in thirty-nine patients at two centers

Modulation of inflammation and metalloproteinase expression in synovial tissue by leflunomide and methotrexate in patients with active rheumatoid arthritis: Findings in a prospective, randomized, double-blind, parallel-design clinical trial in thirty-nine patients at two centers

Co‐stimulatory and adhesion molecules of dendritic cells in rheumatoid arthritis

Treatment of poor-prognosis early rheumatoid arthritis: A randomized study of treatment with methotrexate, cyclosporin A, and intraarticular corticosteroids compared with sulfasalazine alone

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