Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8833062 | Clinical pharmacology of combination DMARD therapy in rheumatoid arthritis. | 1996 Mar | Knowledge about disease modifying antirheumatic drug (DMARD) mechanism(s) of action, kinetics and toxicities can be used to help develop rational DMARD combinations. While limited by the present lack of knowledge in these areas, the present DMARD characteristics will be used to develop rational DMARD combinations. Combinations of methotrexate (MTX) plus azathioprine, and MTX plus gold might be expected to be poor DMARD combinations, a prediction borne out by experimental studies. MTX plus cyclosporine, on the other hand, should be an effective combination, again demonstrated by a recently published clinical study. Also, hydroxychloroquine plus MTX should be a good combination, and an observational study seems to support this. However, not all predictions are accurate (probably due to inadequate data about mechanisms, kinetics, and toxicities). For example, hydroxychloroquine plus D-penicillamine had a negative interaction when tested, a result not predicted by the suggested approach. In addition, predictions are inevitably oversimplified so that what appears to be a negative interaction between MTX and sulfasalazine is not actually one when the details of the potential negative interaction between these 2 drugs are examined. Ultimately, use of a construct such as the one suggested should improve the chances of success and decrease the costs of testing DMARD drug concentrations. | |
| 7761078 | [Low-dose methotrexate therapy of rheumatoid arthritis in the elderly]. | 1995 May 28 | 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. | |
| 8216416 | DAB486IL-2 fusion toxin in refractory rheumatoid arthritis. | 1993 Sep | OBJECTIVE: To evaluate the safety and antiarthritic effects of DAB486IL-2. This agent is a fusion toxin and the product of a synthetic gene, engineered by replacing the codons for the receptor-binding domain of diphtheria toxin (DT) with the codons for human interleukin-2 (IL-2). DAB486IL-2 targets cells expressing the 2-chain, high-affinity form of the IL-2 receptor (IL-2R), and achieves selective diphtheria toxin-mediated cytotoxicity of activated T cells by inhibition of protein synthesis. METHODS: Nineteen patients with rheumatoid arthritis (RA) that had been refractory to methotrexate participated in an open-label, phase I/II trial evaluating 3 dose levels of intravenous DAB486IL-2 given for 5 or 7 consecutive days. Thirteen patients received additional courses, at higher doses if the original response had been inadequate or at an equivalent dose if the original course produced a response, for a total of 38 courses. Arthritis response was assessed at 28 days, with biweekly followup of patients with substantial response (> or = 50% improved) or meaningful response (> or = 25% improved). Laboratory monitoring included measurement of CD4+ cells and circulating shed IL-2R. RESULTS: Nine of 19 patients treated with high- or medium-dose DAB486IL-2 had a substantial or meaningful response after 1 or 2 treatment courses. No significant responses occurred with the low-dose regimen. Clinical benefit was rapid, with full effect noted by 14 days following completion of infusions. Antibodies to DT developed in all patients, or levels of preexisting antibodies were boosted. Adverse effects included transient elevation of transaminase levels (55% of the patients), fever (40%), nausea or anorexia (30%), hypersensitivity (6%), and thrombocytopenia (5%). Repeat courses were associated with less transaminase elevation and were clinically effective despite induction of anti-DT antibodies. CONCLUSION: The results of this open trial provide preliminary evidence for a potential therapeutic effect of DAB486IL-2 in RA, with an acceptable safety profile. Reversible transaminase elevations limit escalation of the dosage beyond 0.1 mg/kg/day. A controlled study of DAB486IL-2 is required to determine the efficacy of this high-affinity IL-2R-targeted fusion toxin in the treatment of RA. | |
| 8184239 | [Fatal outcome of pneumocystis-carinii pneumonia under low-dose methotrexate and prednison | 1994 Apr 12 | New therapeutic schemes have been proposed recently for treatment of rheumatoid arthritis. Among these, methotrexate at low doses is recommended as basic therapy, already shortly after the diagnosis is established. We report on a 68-year-old female with rheumatoid arthritis who developed bilateral pneumocystis-carinii pneumonia with a lethal course and bilateral sinusitis maxillaris with candida lusitaniae. Various opportunistic infections have been described in the literature after low-dose methotrexate. It is our view that the use of methotrexate in rheumatoid arthritis should still be considered cautiously until further data on the risk-benefit ratio of long-term use become available. | |
| 8587070 | Lack of correlation between pharmacokinetics and efficacy of low dose methotrexate in pati | 1995 May | OBJECTIVE: To determine if the variability in the efficacy of methotrexate (MTX) in rheumatoid arthritis (RA) is correlated with its pharmacokinetics. METHODS: MTX pharmacokinetics was evaluated in 46 patients with RA starting a weekly intramuscular low dose MTX treatment. The patients were divided into 32 responders and 14 nonresponders to MTX according to the clinical response in the 6 months after the pharmacokinetic study. MTX plasma (at T0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12 and 24 h) and urine concentrations were measured with the TDx Abbott fluorescence polarization immunoassay. RESULTS: The MTX dosage, age, sex, RA duration, hepatic and renal functions of responders and nonresponders were not different. No difference was found either in peak concentration, residual 24th hour concentration, area under the curve, total body clearance, renal clearance, and terminal T1/2 life of MTX in responders and nonresponders. Surprisingly, patients with adverse reactions had higher total body and renal MTX clearances than those without side effects during the study. CONCLUSION: These data suggest that plasma MTX measurements are not helpful in defining an optimal treatment regimen. | |
| 9036721 | [Low dose methotrexate therapy in chronic polyarthritis--an update]. | 1996 | Since the early eighties methotrexate (MTX) has become of increasing importance in long-term therapy of rheumatoid arthritis (RA) as a disease modifying drug (DMARD). Nowadays it is probably the most frequently prescribed DMARD for RA and can be regarded as the gold standard in long-term therapy. MTX can be administered orally or parenterally, the bioavailability shows high individual differences, but is about 70% after oral administration on average. Its protein-binding amounts to 50%, the main pathway of elimination is renal tubular secretion, to a smaller extent also biliary excretion. MTX polyglutamates are stored intracellularly. Its mode of action in RA is not completely elucidadet yet, besides inhibition of dihydrofolatereductase and consequently inhibition of thymidilate synthesis, some antiinflammatory effects, such as stimulation of Adenosine release from neutrophils, may contribute to the therapeutical effects. MTX' efficacy could be proven by several controlled trials, some of them lasting for more than five years. During long-term therapy with MTX a folate deficiency may occur, which can lead to some side effects. Most important but rarely occurring is pneumonitis, moreover hepatotoxicity and hematological features have to be intensively considered. The risk of the development of osteopenia or an increased incidence of malignancies during MTX therapy is currently investigated. In case of clinical and laboratory controls at regular intervals and patient education MTX therapy can be regarded as effective, well tolerable and considerably safe for patients with rheumatoid arthritis. | |
| 8187436 | Parvovirus infection causing red cell aplasia and leukopenia in rheumatoid arthritis. | 1994 Mar | A case of acute parvovirus B19 infection causing fever, anaemia, leukopenia, and red cell aplasia, in a patient with chronic rheumatoid arthritis is described. The patient had received low doses of corticosteroids for several years, and a small dose of methotrexate recently. There was no evidence of haemolytic anaemia, iron deficiency or drug toxicity. Recovery was associated with the development of antibodies against parvovirus B19, and clearance of viraemia as detected by the polymerase chain reaction. Possible mechanisms for the development of leukopenia are discussed, but there was no evidence for haemophagocytosis. | |
| 8535640 | Combining sulphasalazine and methotrexate in rheumatoid arthritis: early clinical impressi | 1995 Nov | The use of combinations of second line antirheumatic agents (SLAs) is increasing. There are several reasons for combination therapy, e.g. the unsatisfactory effects of single therapy. Strategies for combining SLAs are to begin with combinations, or to add one or more agents to another. The strategy of adding one agent to another is illustrated by a study of 40 patients having insufficient effect from sulphasalazine (SASP). Patients were randomized between methotrexate (MTX) and the combination of SASP and MTX. The patients were evaluated by a single observer in an open design. The follow-up was 24 weeks. The mean decrease in disease activity score was significantly greater and occurred earlier in the combination group. This favourable response was also present in the other efficacy variables. The incidence of toxicity was equal in both groups. These results support the strategy of adding MTX to SASP when combining these second line antirheumatic drugs. | |
| 8091868 | [Side effects and efficiency of 15 mg and 25 mg methotrexate per week in chronic polyarthr | 1994 May | To examine the rate of side effects and the dose dependence of side effects 185 consecutive patients with active rheumatoid arthritis were randomized to receive 15 mg (group A) or 25 mg (group B) methotrexate (MTX) per week and studied prospectively over 12 months. Dose adjustments were performed according to tolerability and efficacy. With 168 patients eligible for evaluation the rate of withdrawal for any reason was 26% in group A and 27% in B. Withdrawal due to side effects occurred in 16% versus 18%, dose reduction due to side effects in 10% versus 9%. The higher dose was associated with a significantly higher rate of gastrointestinal side effects (28% vs. 17%, p < 0.05) and a tendency for more frequent elevations of transaminases. Other side effects were not dose dependent. A significantly higher rate of dose reduction due to improvement (35% versus 10%, p < 0.001), a more rapid decline of morning stiffness, and a higher number of patients reporting marked improvement are evidence in favour of higher therapeutic efficacy of the higher dose. In conclusion, an initial dose of 25 mg MTX/week is not associated with a higher rate of limiting side effects as compared with 15 mg/week. The efficacy of doses up to 25 mg/week should be examined in more detail. | |
| 8972245 | Use of methotrexate in older patients. A risk-benefit assessment. | 1996 Dec | Methotrexate is eliminated almost entirely by the kidneys. The risk of methotrexate toxicity is therefore increased in patients with poor renal function, most likely as a result of drug accumulation. Declining renal function with age may thus be an important predictor of toxicity to methotrexate. Up to 60% of all patients who receive methotrexate for rheumatoid arthritis (RA) discontinue taking it because of adverse effects, most of which occur during the first year of therapy. Gastrointestinal complications are the most common adverse effects of methotrexate, but hepatotoxicity, haematological toxicity, pulmonary toxicity, lymphoproliferative disorders and exacerbation of rheumatic nodules have all been reported. Decreased renal function as a result of disease and/or aging appears to be an important determinant of hepatic, lymphoproli ferative and haematological toxicity. Concomitant use of low doses of folic acid has been recommended as an approach to limiting toxicity. Interactions between methotrexate and several nonsteroidal anti-inflammatory drugs have been reported, but they may not be clinically significant. However, caution is advised in the use of such combinations in patients with reduced renal function. More serious toxicities (e.g. pancytopenia) may result when other inhibitors of folate utilisation [e.g. cotrimoxazole (trimethoprim-sulfamethoxazole)] or inhibitors of renal tubular secretion (e.g. probenecid) are combined with methotrexate. Before starting low dose methotrexate therapy in patients with RA, a full blood count, liver function tests, renal function tests and chest radiography should be performed. Blood counts and liver function tests should be repeated at regular intervals. Therapeutic drug monitoring of methotrexate has also been suggested as a means of limiting toxicity. Patients with RA usually respond very favourably to low dose methotrexate therapy, and the probability of patients continuing their treatment beyond 5 years is greater than for other slow-acting antirheumatic drugs. Thus, given its sustained clinical utility and relatively predictable toxicity profile, low dose methotrexate is a useful addition to the therapy of RA. | |
| 1414040 | [Data of two years of the comparative study methotrexate/aurothiomalate in 102 patients]. | 1992 Jul | 102 patients (pat.) with active erosive rheumatoid arthritis (RA) with a median disease duration of only 14 months without malalignment or deformities entered a randomized study to compare the effects of 15 mg methotrexate (MTX) and 50 mg gold sodium thiomalate (GST) administered intramuscularly once a week. The study was double blind during the first year and open during the second year. Clinical and laboratory evaluations were made every three months. X-rays of hands, wrists and forefeet in standard a.p.-projection were taken at month 0, 6, 12 and 24. 32 joints were evaluated according to Larsen. 17/52 (MTX) and 21/50 (GST) patients were withdrawn for several reasons. Withdrawals for toxicity were significantly more frequent in the GST group. 35 patients in the MTX group and 26 patients in the GST group were evaluated for efficacy. All clinical parameters, ESR and CRP improved by more than 50% in both groups without significant intergroup difference. The greatest improvement was seen already after six months. An > 50% improvement occurred in 57% of pat. in both groups. The Larsen score (sum of the Larsen grades of 32 joints) deteriorated significantly in both groups during the first six months (MTX = 3.0, GST = +4.3), it remained stable thereafter in the MTX group and decreased in the gold group. The number of erosive joints increased significantly in both groups during the first six months. This increase was slowed down after six months in the MTX group, in the gold group a decrease was seen indicating a healing of erosions. All differences between the groups were not significant, however. CONCLUSION: While tolerability was better with MTX, both drugs were similarly effective in the treatment of RA and slowed down radiologic progression. | |
| 7699621 | Effects of low dose methotrexate therapy on the concentration and the glycosylation of alp | 1994 Dec | OBJECTIVE: The concentration, and the degree of fucosylation and sialylation of human serum alpha 1-acid glycoprotein (AGP) were investigated for changes during 24-week low-dose methotrexate (MTX) or azathioprine treatment (AZA) in rheumatoid arthritis (RA) patients. METHODS: Serum samples from a longitudinal study were analyzed by crossed affinoimmunoelectrophoresis with the fucose specific Aleuria aurantia lectin. RESULTS: In general, the degree of fucosylation of AGP in RA sera was higher than in control sera, but decreased markedly under the influence of successful therapy with MTX. Concomitantly, the degree of sialylation of AGP increased and the concentration decreased. For alpha 1-protease inhibitor and haptoglobin similar results were obtained. In AZA responders less pronounced changes than in MTX responders were observed. In MTX nonresponders no significant trends were found. As in control sera, large interindividual differences in the AGP values were found. CONCLUSION: The heavy fucosylation of AGP in RA sera reflects disease activity rather than an intrinsic characteristic of people genetically predisposed to RA, since it was found to decrease upon disease improvement. The differences in effects on AGP of MTX and AZA suggest either a gradual difference in a similar mechanism of action, or a different mechanism of action of the drugs. Fucosylated and sialylated AGP could be important in the etiopathogenesis of RA, because these molecules potentially can bind to adhesion receptors (selectins), which could prevent the extravasation of leukocytes into inflamed joints. | |
| 8857074 | A limited sampling method to estimate methotrexate pharmacokinetics in patients with rheum | 1996 | This paper describes a methodology to calculate methotrexate (MTX) pharmacokinetic parameters after intramuscular administration using two samples and the population parameters. Total and free MTX were measured over a 36-h period in 56 rheumatoid arthritis patients; 14 patients were studied after a two-dose scheme at 15-day intervals. The Hill equation was used to relate the free MTX to the total MTX changes in plasma concentrations, and a two-compartment open model was used to fit the total MTX plasma concentrations. A non-linear mixed effect procedure was used to estimate the population parameters and to explore the interindividual variability in relation to the following covariables: age, weight, height, haemoglobin, erythrocyte sedimentation rate, platelet count, creatinine clearance, rheumatoid factor, C-reactive protein, swelling joint count, and Ritchie's articular index. Population parameters were evaluated for 40 patients using a three-step approach. The population average parameters and the interindividual variabilities expressed as coefficients of variation (CV%) were: CL, 6.94 l center dot h-1 (20.5%); V, 34.8 l (32.2%); k12, 0.0838 h-1 (47.7%); k21, 0.0769 h-1 (61.6%); ka, 4.31 h-1 (58%); Emax, 1.12 mu mol center dot l-1 (19.7%); gamma, 0.932 (12.3%); and EC50, 2.14 mu mol center dot l-1 (27.3%). Thirty additional data sets (16 new patients and 14 patients of the previous population but treated on a separate occasion) were used to evaluate the predictive performance of the population parameters. Twelve blood samples were collected from each individual in order to calculate individual parameters using standard fitting procedures. These values were compared to the ones estimated using a Bayesian approach with population parameters as a priori information together with two samples, selected from the individual observations. The results show that the bias was not statistically different from zero and the precision of these parameters was excellent. | |
| 7664026 | Circulating interleukin 10 and interleukin-6 serum levels in rheumatoid arthritis patients | 1995 Jan | In order to evaluate the relationship between serum concentrations of interleukin-10 (IL-10), IL-6, and acute phase proteins in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) or intramuscular gold (IMG) we determined IL-10, IL-6, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP) and alpha-1-antichymotrypsin (ACT) in the sera of 35 RA patients. IL-10 and IL-6 levels were evaluated using an enzyme-linked immunoassay (ELISA). AGP and ACT level were measured using rocket immunoelectrophoresis. IL-10 serum level was not increased in RA patients as compared to controls (58.7 +/- 18.1 pg/ml vs. 57.2 +/- 11.9 pg/ml). IL-6 level was significantly elevated (91.6 +/- 46.9 pg/ml vs. 45 +/- 19 pg/ml, p < 0.05). CRP was significantly increased as compared to healthy controls (35 +/- 19 mg/l vs. 3 +/- 2 mg/l, p < 0.05). Patients treated with MTX or IMG presented an increased level of IL-10 and decreased amounts of IL-6, as compared to those treated with NSAID only. However, only changes between patients treated with IMG and NSAID were found to be statistically significant. A good negative correlation between IL-10 and IL-6 serum level was found (r = -0.75, p < 0.05). A positive significant correlation between IL-6 serum level and CRP (r = 0.62, p < 0.05), AGP (r = 0.78, p < 0.05) and ACT (r = 0.45, p < 0.05) was established.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 8630820 | [The combined use of diprospan and laser irradiation of the joints in rheumatoid arthritis | 1995 May | An evaluation was done of effectiveness of diprospane (prolonged action glucocorticosteroid) in rheumatoid arthritis. There have been studied parameters characterizing the articular syndrome, laboratory values during the course of complex therapy that incorporated intraarthrous administration of diprospane and a course of laser irradiation of the joints against a background of intake of non-steroid antiinflammatory preparations and basis therapy with methotrexate. Topical therapy incorporated into the complex of therapeutic measures applied in patients with rheumatoid arthritis was found to be associated with most stable and pronounced effect, especially in the arthrous form of the malady. Combined use of intraarthrous administration of diprospane and a course of laser therapy permits achieving a favourable effect after a single administration of this drug preparation. | |
| 8832981 | Effects on fibrogenesis markers of rheumatoid arthritis therapy with methotrexate. | 1996 Mar | OBJECTIVE: To evaluate the level of 2 serum markers of hepatic fibrogenesis, aminoterminal peptide of type III procollagen (NPIIIP) and laminin P1 fragment (Lam), in patients with rheumatoid arthritis at baseline and after one year of low dose methotrexate (MTX) therapy. METHODS: Serum levels of NPIIIP and Lam were measured in 20 patients, 17 women and 3 men, mean age 48.83 +/- 9.25 yrs. before and after MTX treatment and compared to levels from 20 sex and age matched, healthy controls. RESULTS: The baseline values of NPIIIP was higher in patients than in controls; it normalized after MTX treatment. The Lam level did not differ between patients and controls; moreover, it did not change after treatment. CONCLUSION: Low dose MTX therapy does not increase serum indicator levels of hepatic fibrogenesis. | |
| 10130384 | An approach to preventing methotrexate prescribing errors in rheumatoid arthritis. | 1993 Nov | Methotrexate is an effective treatment for rheumatoid arthritis and is fairly well tolerated by patients when used appropriately. However, errors do occur due to a lack of awareness of the normal dosage range and potentially serious dose related side effects of methotrexate among physicians, pharmacists, and nurses. The approach taken by one hospital to prevent methotrexate prescribing errors includes daily monitoring of methotrexate by a pharmacist, building caution flags in the order loading program of the pharmacy computer system, and educating healthcare professionals to heighten awareness when prescribing, dispensing, and administering methotrexate for rheumatoid arthritis. At the hospital, since the institution of these policies and education of pharmacists, nurses, and physicians, there have been no incidents of methotrexate prescribing errors. | |
| 8212923 | Transient increase of aminotransferases in RA patients treated with methotrexate. | 1993 Jul | Sixty-two patients with rheumatoid arthritis (RA) were treated with methotrexate (MTX) for 3 months. Methotrexate was given orally in a single dose of 7.5-15.0 mg/week. At the onset of the treatment increased activity of aminotransferases has been observed. Eighteen patients (29%) displayed higher enzyme activity in the first 3 weeks. Despite the continuous drug administration the activity of aminotransferase became normal at week 12 in all but one patient. In this patient MTX had to be withdrawn. | |
| 1314609 | Acute and chronic suppression of leukotriene B4 synthesis ex vivo in neutrophils from pati | 1992 Apr | OBJECTIVE: To compare the cumulative effects of oral methotrexate (MTX) therapy (after 6-8 weeks) with the acute effects (24 hours after a dose) on arachidonic acid metabolism by the 5-lipoxygenase (5-LO) pathway in neutrophils from patients with active rheumatoid arthritis (RA) who were beginning therapy with MTX. METHODS: Neutrophils and monocytes were isolated from whole blood from 7 patients with RA, immediately before and 24 hours after their first weekly dose of 7.5 mg of MTX, and again after their dose at 6-8 weeks. RESULTS: Total immunoreactive leukotriene B4 (LTB4) formation in neutrophils activated ex vivo with calcium ionophore A23187 was significantly suppressed (by 33%) before the 6-8-week dose, compared with the level before the first dose (mean +/- SEM 8.29 +/- 1.24 ng/10(6) cells at predose 6-8 weeks versus 12.29 +/- 2.13 ng/10(6) cells at predose 1; P = 0.03). Reductions were also observed after the first dose (27%; P = 0.07) and after the 6-8-week dose (43%; P = 0.05) compared with the respective predose levels. MTX treatment produced significant reductions in the total generation of 5-LO pathway products (5-hydroxyeicosatetraenoic acid + 6-trans-LTB4 + LTB4 + omega-oxidation products of LTB4) by calcium ionophore-activated neutrophils, as quantitated by integrated optical density after resolution on reverse-phase high-performance liquid chromatography. Decreases were observed after the first dose (26%; P = 0.025), immediately before the 6-8-week dose (23%; P = 0.05), and after the 6-8-week dose (47%; P = 0.0033) compared with levels before the first dose, and after the 6-8-week dose compared with the level before it (32%; P = 0.04). The generation of LTB4 by calcium ionophore-activated monocytes was not significantly affected by MTX therapy. CONCLUSION: The significant decreases in the formation of omega-oxidation products of LTB4 and in the total generation of neutrophil 5-LO pathway products in the absence of a significant change in the release of 3H-arachidonic acid or the generation of platelet-activating factor suggest that the activity of the 5-LO enzyme in neutrophils is inhibited. We conclude that weekly oral MTX therapy in patients with active RA inhibits neutrophil 5-LO pathway product generation in a pattern consistent with inhibition of the activity of the 5-LO enzyme; an effect is observed after the first dose. The inhibition of 5-LO is cell-selective and cumulative, with a superimposed incremental inhibition observed after the weekly MTX dose. | |
| 7978695 | Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A do | 1994 Dec 1 | OBJECTIVE: To determine the effect of two different weekly doses of folic acid on the toxicity and efficacy of low-dose methotrexate therapy for rheumatoid arthritis. DESIGN: Randomized, double-blind, placebo-controlled study. PATIENTS: 79 persons between 19 and 78 years of age who fulfilled the American Rheumatism Association's criteria for rheumatoid arthritis. INTERVENTION: Participants were randomly assigned to visually identical placebo or to 5 mg or 27.5 mg of folic acid each week. MEASUREMENTS: Duration, intensity, and clinical severity of toxic events; efficacy (indices of joint tenderness and swelling and grip strength); plasma and erythrocyte folate levels; and other laboratory variables. RESULTS: Folic acid supplementation at either dose did not affect the efficacy of methotrexate therapy as judged by joint indices and patient and physician assessments of disease. Patients given folic acid supplements had lower toxicity scores than did participants given placebo (P < or = 0.001). Low blood folate levels and increased mean corpuscular volumes were associated with substantial methotrexate toxicity, whereas daily dietary intakes of more than 900 nmol (400 micrograms) of folic acid were associated with little methotrexate toxicity. CONCLUSIONS: Folic acid, an inexpensive vitamin, is safe in a broad range of doses and protects patients with rheumatoid arthritis who are taking methotrexate from toxicity while preserving the efficacy of methotrexate. |