Influence of methotrexate dose on its efficacy and safety in rheumatoid arthritis patients: evidence based on the variety of prescribing approaches among practicing Japanese rheumatologists in a single institute-based large observational cohort (IORRA)
Hisashi YamanakaEisuke InoueEiichi TanakaAyako NakajimaAtsuo TaniguchiChihiro TeraiMasako HaraTaisuke TomatsuNaoyuki Kamatani
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Abstract:
The optimal methotrexate dose differs between rheumatoid arthritis (RA) patients, and dose-escalation strategies also differ among rheumatologists. By taking advantage of the heterogeneous methotrexate dosing that occurs among Japanese rheumatologists, we analyzed the efficacy and safety of different methotrexate doses. A large observational cohort of RA patients, IORRA, was established in 2000. A dataset from April 2003 that included 4578 RA patients was used for a cross-sectional analysis, while a dataset of 1649 patients who received methotrexate from October 2000 to October 2005 was used for a longitudinal analysis. The cross-sectional analysis included 12 rheumatologists who prescribed methotrexate to more than 60 patients. Mean methotrexate dose ranged widely (4.8–9.0 mg/week) among rheumatologists with a significant positive relationship between average methotrexate dose and the percentage of patients with Disease Activity in 28 Joints (DAS28) scores below 3.2. During the longitudinal analysis, both methotrexate prescription frequency and the average dose prescribed by 16 rheumatologists increased. Overall disease activity as assessed by DAS28-area under the curve (AUC) and disability progression as assessed by Japanese version of the Health Assessment Questionnaire (JHAQ)-slope inversely correlated with the extent of methotrexate use. This study demonstrated that extensive methotrexate use effectively suppressed RA disease activity and inhibits disability progression. In addition, we have found that it is critical to pay attention to patient-reported adverse reactions.Keywords:
Cross-sectional study
Objective. To determine whether patients with early rheumatoid arthritis (RA) treated with cyclosporin A (CsA) and methotrexate (MTX) in combination for 12 months show a lower rate of radiographic deterioration than those treated with MTX alone.
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Two years results of methotrexate treatment (13 patients, 7.5-10 mg weekly dose) in elderly onset rheumatoid arthritis are reported in comparison to other therapies (10 patients, im. gold 50 mg weekly or per os steroid max. 10 mg daily). Clinical activity of rheumatoid arthritis was measured with standard rheumatological parameters whereas progression of the disease was defined by means of a radiological method. Methotrexate caused better clinical improvement and retarded progression to a greater extent than the other therapies. Methotrexate achieved its maximum effect during the first 6 months of therapy. Methotrexate was well tolerable. Long term applicability of low dose methotrexate treatment in elderly age is emphasized.
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In methotrexate-treated patients with rheumatoid arthritis (RA), how does the addition of a biologic agent compare with addition of two conventional nonbiologic agents? This question was addressed in a double-blind, placebo-controlled, randomized trial that involved 353 RA patients who had received 15 to 25 mg of methotrexate weekly for at least 12 weeks and who …
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Objective To explore the efficacy and safety of leflunomide combined with methotrexate in the treatment of rheumatoid arthritis.Methods 120 patients with active rheumatoid arthritis were randomly divided into a treatment group(n=60) and a control group(n=60).The treatment group was treated with leflunomide and methotrexate,while the control group with only methotrexate.The efficacies and adverse reactions compared between two groups.Results The total effective rate was 88.3％ in the treating group and was 71.7％ in the control group,with a statistical difference(P＜0.05).The incidence of adverse reactions was 25％ in the treating group and was 20％ in the control group,with no statistical difference (P＞0.05).Conclusion Leflunomide combined with methotrexate in the treatment of rheumatoid arthritis is effective and worth being clinically generalized.
Key words:
Rheumatoid arthritis; Leflunomide; Methotrexate
Leflunomide
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Objective To investigate the protective effect of methotrexate on probable rheumatoid arthritis (RA) patients. Methods 62 probable rheumatoid arthritis (RA) patients were randomly divided into two groups, treatment group (32 cases) accepted methotrexate and non-steroidal anti-inflammatory drug and control group only non-steroidal anti-inflammatory drug. In the 2-year follow-up visit, patients who developed to RA would withdraw and accept normal combined medicine treatment. They were assessed with X-ray changes of the hand joints. Results 8 cases of the treatment group developed RA (2 cases withdrew because of intolerance), while 17 cases of the control group developed RA. The treatment group developed RA later than the control group, with less radiographic joints injury in 2 years. Conclusion Methotrexate can delay clinical process of the development of RA in the probable RA patients and reduce joints damage.
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Abstract Methotrexate is a cytostatic agent used mainly in treatment of neoplasms. However, it has also been applied in treatment of diseases of autoimmune aetiology. The present paper is a review concerning the application of methotrexate in treatment of rhewnatoid arthritis. The authors are trying to determine the role of the drug in the therapy of rheumatoid arthritis at present and in future.
Etiology
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Five patients with oligoarticular rheumatoid arthritis were treated with intra-articular injections of methotrexate and orgotein in the knee joints. The employed dose of the antimetabolite was very low and orgotein was simultaneously administered to prevent local tissues from cytolysis-related damage. Clinical results were fairly good and support the hypothesis that methotrexate may be used intra-articularly as an immunosuppressor rather than at the heavily toxic doses required for a cytostatic effect.
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Rheumatic disease
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Methotrexate has become the agent of choice for rheumatoid arthritis that does not respond to nonsteroidal anti-inflammatory drugs. In appropriately selected patients and with diligent monitoring, methotrexate in low weekly doses is effective and has a much better safety profile than was originally perceived.
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