Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1921823 | Pancytopenia after accidental overdose of methotrexate. A complication of low-dose therapy | 1991 Oct 7 | OBJECTIVE: Pancytopenia is an unusual complication of low-dose methotrexate therapy in rheumatoid arthritis. We report a near fatal case that followed an accidental overdose. CLINICAL FEATURES: An 80-year-old Caucasian woman with rheumatoid arthritis presented with pancytopenia and severe mucositis. She had taken her weekly methotrexate dose on four sequential days, due to an error in filling a "Dosette" box. INTERVENTION AND OUTCOME: Following treatment with piperacillin, gentamicin and folinic acid, she recovered completely. CONCLUSIONS: Low-dose methotrexate therapy is uncommonly associated with haematological toxicity. This generally occurs in patients with known risk factors for such reactions. Patient reliability should be considered if methotrexate therapy is contemplated. | |
| 2531058 | [The combination of cyclosporin A and fluocortolone in the treatment of autoimmune disease | 1989 Oct 15 | The authors report the results obtained in treatment of various autoimmune diseases using cyclosporin A (CyA) in association with fluocortolone and/or methotrexate and cyclophosphamide. In all patients treated, complete long-lasting remission of the disease both from a clinical point of view and regarding laboratory tests was obtained. In some cases, this remission has lasted for several years since onset of therapy. The results obtained demonstrate the efficacy of CyA in treatment of autoimmune diseases and show that association with fluocortolone and/or methotrexate and cyclophosphamide by exploiting the combined action of these drugs, has enabled relatively low doses to be used. These however are still sufficient to induce satisfactory immunosuppression and avoid side effects. In this context, the importance of monitoring drug blood levels is underlined, also in view of the fact that each patient has a different capacity for intestinal CyA absorption. | |
| 3245825 | Pancytopenia induced by low-dose methotrexate for rheumatoid arthritis. | 1988 Aug | Four cases of pancytopenia related to low-dose weekly pulse methotrexate therapy for rheumatoid arthritis are described. All patients were aged above 60 years and had renal impairment. In every case marrow recovery followed withdrawal of methotrexate. However, one patient developed pneumonitis and died. Cholangitis, respiratory infection and increase in methotrexate dose were precipitating factors. Pharmacokinetic data indicated prolonged tissue drug exposure in two cases studied; dose-related toxicity was further supported by successful resumption of methotrexate in reduced dosage in two cases. It is possible that methotrexate dose should be modified during intercurrent illness in patients older than 60 years who have renal impairment. | |
| 2302272 | Pharmacokinetics of methotrexate administered by intramuscular and subcutaneous injections | 1990 Jan | The serum concentrations and the pharmacokinetics of low-dose methotrexate (MTX) were compared after both intramuscular (IM) and subcutaneous (SQ) injections in 5 patients with rheumatoid arthritis. Values for the observed peak concentration, the time to the observed peak concentration, and the area under the time versus concentration curve for IM injections were not significantly different from these values for SQ injections. These results suggest that IM and SQ are interchangeable routes of administration. SQ administration may be a more convenient and less painful way of administering low-dose MTX. | |
| 2772658 | Prospective analysis of liver biopsies before and after methotrexate therapy in rheumatoid | 1989 Aug | The significance of hepatic changes in methotrexate-treated RA patients is unclear at this time. In our group of RA patients, there was a slight increase in the incidence of triaditis and fat during methotrexate therapy. Disease duration greater than or equal to 10 years was associated with increased hepatic triaditis before treatment. Age greater than 50 years was associated with increased hepatic fat before and after treatment. It appears that patients' ages and duration of underlying RA account for some changes, independent of methotrexate therapy. Several of our patients changed from higher to lower histologic grade or had an apparent decrease in fibrosis, fat, or triaditis on the pathologists' reports and the blind readings of the repeat biopsies. This may be explained by sampling error. More importantly, some of these changes may not be of clinical significance. One report of methotrexate-induced cirrhosis in patients with psoriasis demonstrated that in all but one of 14 patients who continued receiving methotrexate the cirrhosis decrease or did not progress. This may also be true of the hepatic fibrosis seen in RA after methotrexate treatment. In this study, there did not appear to be changes seen on pretreatment liver biopsy that were predictive of subsequent fibrosis or cirrhosis. Our data indicate that pretreatment biopsy is unwarranted in a population similar to ours. However, our practice has been to try to avoid methotrexate in patients with diabetes, prior liver disease, alcoholism, or obesity because of previous reports suggesting that these patients are at increased risk for the development of cirrhosis. Only the above-mentioned patient, eventually diagnosed as having cirrhosis, might have been handled differently. Including the study, none of the approximately 700 RA patients in the literature having liver biopsies after methotrexate therapy have developed cirrhosis consequent to its use. Most of these had received a total dose of approximately 1,500 mg in small weekly doses, and alcohol was prohibited. Below this cumulative dose the risk of clinically significant liver damage in carefully selected patients is very low. In view of this experience, the recommendation that RA patients have liver biopsies after 1,500 mg of methotrexate (a holdover from the psoriasis literature) may be too conservative in low-risk RA patients, provided methotrexate is administered weekly and alcohol is prohibited. Recognizing that the absolute need for biopsy is unproven, a more realistic milestone for those choosing biopsy might be after each 2,000 to 2,500 mg.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 3052323 | Life threatening acute pneumonitis during low dose methotrexate treatment for rheumatoid a | 1988 Sep | A patient is described with definite rheumatoid arthritis (RA) who developed life threatening acute pneumonitis after receiving a total dose of only 12.5 mg methotrexate (MTX). This complication has been previously described, but this is probably the lowest reported dose before development of pneumonitis in a patient with RA. The possible significance of this case is discussed in the light of recent reports suggesting an increased susceptibility of patients with RA to the pulmonary toxicity of MTX. | |
| 1787499 | Lymphoma developing in a patient with rheumatoid arthritis taking low dose weekly methotre | 1991 Nov | We describe the occurrence of a lymphoma in a patient with rheumatoid arthritis (RA) taking weekly oral pulse methotrexate (MTX) in low doses for 33 months. This occurrence may be coincidental. There may be an increased incidence of lymphoma in RA not treated with immunosuppressive medications. However, the increasing use of MTX warrants reporting unusual events, especially malignancy. It is possible that even the mild immunosuppression that occurs with MTX therapy places patients with RA at added risk for developing lymphoproliferative diseases. | |
| 3195601 | Methotrexate-associated hepatotoxicity: retrospective analysis of 210 patients with rheuma | 1988 Dec | PURPOSE: Beginning in the 1980s, methotrexate has been used successfully to treat rheumatoid arthritis. The magnitude and severity of short- and long-term methotrexate toxicity, however, have not been adequately investigated. Our study was performed to determine the prevalence of hepatotoxicity in patients with rheumatoid arthritis receiving long-term methotrexate therapy. PATIENTS AND METHODS: We conducted a retrospective, computer-assisted review of all Duke University Medical Center patients undergoing liver biopsy for methotrexate monitoring from January 1979 to January 1988. A total of 538 biopsies were performed in 399 patients, 259 of whom had inflammatory arthritis (210 with rheumatoid arthritis, 47 with psoriatic arthritis, and two with seronegative spondyloarthropathy). RESULTS: No evidence of cirrhosis was defined in the cohort with rheumatoid arthritis; however, six patients with rheumatoid arthritis had histologic changes of fibrotic liver disease (prevalence of 2.9 percent in the group with rheumatoid arthritis) while taking methotrexate. Five of the six patients were obese and three had glucose intolerance or overt diabetes mellitus, and one person admitted to alcohol usage. Only one patient with fibrotic liver disease had elevated liver function test results, and no person showed a declining serum albumin level at the time of biopsy. Sixty-one patients with rheumatoid arthritis underwent multiple samplings (44 with two, 13 with three, and four with four biopsies). Fourteen of these patients showed progressive hepatic disease, whereas four patients improved. CONCLUSION: Although the prevalence of methotrexate hepatotoxicity in this large cohort of patients with rheumatoid arthritis was low, a small but definite risk of hepatic fibrosis, not predictable by laboratory screening, still exists. | |
| 2570580 | Combination methotrexate and sulfasalazine in the management of rheumatoid arthritis: case | 1989 Sep | Four patients with rheumatoid arthritis received a combination of methotrexate and sulfasalazine for a mean of 24 months (range 20-28 months). All 4 patients experienced clinical improvement, with a reduction in the number of involved joints and in morning stiffness. In all 3 patients who had previously taken methotrexate, we were able to reduce the dosage, and the prednisone dosage was reduced in 2 of 3 patients who had previously taken that drug. No serious toxicity was observed in any patient. | |
| 2244252 | [Low dose methotrexate therapy in rheumatoid arthritis]. | 1990 Jun | Twenty-three patients were included in this prospective study about the safety and efficacy of oral low dose methotrexate (MTX) in the treatment of refractory rheumatoid arthritis. Patients received a mean dosage of 6.6 +/- 1.8 (SD) mg weekly over a mean duration of 16.6 +/- 12.5 months. Patients improved significantly in all clinical parameters of efficacy. There were significant reductions in Lansbury joint scores (p less than 0.001), duration of morning stiffness (p less than 0.001), sedimentation rates (p less than 0.001), C-reactive protein (p less than 0.01), IgG(p less than 0.01), rheumatoid factor (p less than 0.01) and significant increase in grip strength (p less than 0.001), hemoglobin (p less than 0.05) after 17 months of treatment with MTX. Radiographic progression of joint disease were assessed using global scoring method. The mean rate of development of erosions and joint-space narrowing during MTX therapy was significantly less than the rate of radiographic progression before MTX therapy (8.1 +/- 7. 9/year vs. 1.9 +/- 3.8; p less than 0.05). Adverse reactions during MTX therapy included transient transaminase elevation (17.4%). Five patients (21.7%) were withdrawn because of leukopenia (2), interstitial pneumonitis (1), stomatitis (1), skin rash (1). We conclude that low-dose methotrexate is effective for the management of clinical disease activity in patients with refractory rheumatoid arthritis and may be a disease-modifying anti-rheumatic drugs (DMAR-Ds) by roentgenographic criteria. | |
| 2175662 | Combination D-penicillamine and methotrexate therapy: proposal for early and aggressive tr | 1990 Fall | We report a retrospective study of 16 patients with seropositive rheumatoid arthritis who were placed on combination D-penicillamine and methotrexate therapy for a period of 5-86 months. Three patients were lost to follow-up, and one patient died of unknown causes at another institution. Among the 12 remaining patients, there was no withdrawal secondary to drug intolerance. All patients demonstrated improvement in functional class correlated with a reduction in joint count, duration of morning stiffness, erythrocyte sedimentation rate, rheumatoid factor, and prednisone requirement. Eight of the 12 patients achieved remission as defined by the American College of Rheumatology criteria. Remission was sustained for a period of 3-72 months. The dosage of D-penicillamine ranged from 250-1000 mg/d (mean = 750 mg); that of methotrexate ranged from 5-15 mg/week (mean = 10 mg). The study indicates that D-penicillamine and methotrexate combination therapy is effective in the treatment of severe rheumatoid arthritis and warrants further prospective investigation. | |
| 3772918 | The effect of low dose chronic intermittent parental methotrexate on delayed type hypersen | 1986 Aug | We have shown that a regimen of low dose intermittent methotrexate (MTX), analogous to that used in the treatment of patients with rheumatoid arthritis, does have immunosuppressive effects on the induction of primary delayed type hypersensitivity in normal mice. This occurred even when the last MTX injection was 4 days before immunization. No effect was seen on established delayed type hypersensitivity or on inflammatory responses induced by carrageenan or the Arthus reaction. | |
| 2192056 | Drug-drug interactions with antirheumatic agents: review of selected clinically important | 1990 May | Drug therapy for rheumatoid arthritis (RA) often requires the use of more than one drug, thus drug-drug interactions are very likely in this patient population. We discuss the pharmacokinetic and pharmacodynamic mechanisms involved in drug-drug interactions. Our review focuses on selected examples involving drugs used to treat RA and other antirheumatic drugs [e.g., methotrexate and nonsteroidal antiinflammatory drugs (NSAID)] or with other therapeutic classes of drugs (e.g., NSAID and warfarin). Studies and case reports of drug-drug interactions with antirheumatic drugs are critically evaluated and the potential clinical implications are discussed. | |
| 3196364 | Histopathologic findings in the liver of rheumatoid arthritis patients treated with long-t | 1988 Dec | Twenty-three patients with severe rheumatoid arthritis were treated with oral methotrexate (MTX) for more than 10 years. MTX was given as a bolus of 5-15 mg/week; the total cumulative dose ranged from 4,690 mg to 10,230 mg. Liver biopsies were performed on 21 of the patients to assess possible fibrosis and cirrhosis. Grade I histopathologic changes were found in 13 of the 21 biopsy samples, grade II changes were found in 3, and grade IIIA changes (mild fibrosis) were found in 5 specimens. None of the biopsy samples showed cirrhosis. Repeat biopsies were performed on the 5 patients with grade IIIA changes while they were still taking MTX. No progression of the fibrosis was noted. Two of the 5 samples, however, were graded IIIB because of portal and perilobular inflammation. Our findings support the premise that prolonged administration of oral MTX, when given as a weekly bolus at a low dose, does not cause cirrhosis or severe fibrosis in the rheumatoid arthritis patient who does not abuse alcohol. | |
| 3551606 | Severe flare of rheumatoid arthritis after discontinuation of long-term methotrexate thera | 1987 Apr | To determine if long-term methotrexate-induced improvement of rheumatoid arthritis is sustained after the drug is discontinued, 10 unselected patients with responses to weekly oral methotrexate given for at least 36 months (mean 40.1) were randomly assigned to receive methotrexate or identical-appearing placebo tablets for two months. After one month, all five patients receiving placebo had to have the study terminated due to a flare of their disease manifested by statistically significant deterioration in multiple clinical parameters. It is concluded that patients receiving long-term methotrexate must continue the drug to maintain clinical benefits. | |
| 1745087 | [Rheumatoid arthritis and multiple neoplasms]. | 1991 Sep 28 | In patients with rheumatoid arthritis the appearance of neoplastic disease has been fundamentally described of lymphoproliferative origin. The case of a 59 year old woman with rheumatoid arthritis of a 4 year evolution is reported. The patient was treated with gold salts and methotrexate and presented successively a bronchogenic carcinoma and a non-Hodgkin lymphoma. The epidemiologic studies in the relation of rheumatoid arthritis-neoplasia are discussed and the pathogenic hypotheses to the immune alterations as well as the treatments employed are described. | |
| 2192058 | Longterm experience with low dose weekly methotrexate in rheumatoid arthritis. | 1990 May | Longterm prospective studies (several of greater than 5 years' duration) report sustained efficacy with low dose weekly methotrexate. A "steroid-sparing" effect has been noted with methotrexate in 2 of the studies. Of 230 patients enrolled in prospective studies, only 8% stopped therapy due to toxicity and 3% due to lack of efficacy. Life table analysis projected that 63% of these patients would receive therapy for 6 years. Even though adverse experiences were frequent, serious reactions have been rare in the published studies. | |
| 2585411 | Acute, reversible hepatic failure associated with methotrexate treatment of rheumatoid art | 1989 Aug | We describe 2 patients who developed reversible decompensated liver disease while taking pulse dosed methotrexate (MTX) for rheumatoid arthritis. One of the patients was available for biopsy and had chronic active hepatitis--a lesion not previously described with MTX. This appears to be a unique and unusual manifestation of MTX hepatotoxicity. | |
| 2498513 | Gold sodium thiomalate compared to low dose methotrexate in the treatment of rheumatoid ar | 1989 Mar | Thirty-five patients with definite or classic rheumatoid arthritis (RA) entered a prospective, double blind, randomized study of 26 weeks duration. All patients had active RA that was unresponsive to greater than or equal to 2 nonsteroidal antiinflammatory medications and/or antimalarials. Eighteen patients were randomized to receive methotrexate (MTX) 12.5 mg weekly (oral and noncycled) + placebo, and 17 patients to gold sodium thiomalate (GSTM) 50 mg IM weekly + placebo (schedule I) after initial test dose of 10 and 25 mg. Dose reductions from Schedule I to Schedule II (i.e. MTX 5.0 mg and GSTM 25 mg) were permitted at Weeks 6 and 12. The GSTM group showed statistically significant improvement at Week 26 compared with baseline status in all of the clinical efficacy variables and the MTX group in 7. There were no statistically significant differences in these outcome variables between the 2 groups at Week 26. However, this small sample size may not have detected a clinically significant difference between treatment groups (alpha = 0.05, beta = 0.20). Two of the 18 patients treated with MTX and 6 of the 17 patients treated with gold withdrew because of drug toxicity, but this difference was not statistically significant. In conclusion, GSTM and MTX are similarly efficacious in the short term treatment of RA. | |
| 3304050 | Methotrexate in rheumatoid arthritis. Indications, contraindications, efficacy, and safety | 1987 Sep | Evidence on the safety and efficacy of methotrexate as a second- or third-line agent for treating patients with rheumatoid arthritis is reviewed. Four placebo-controlled clinical trials have documented short-term benefit from methotrexate; although true remission is rare, patients receiving methotrexate showed a 26% (95% confidence interval [CI], 17% to 35%) greater improvement in their inflamed joint count and a 39% (95% CI, 26% to 51.5%) greater improvement in pain than did controls receiving nonsteroidal anti-inflammatory agents with or without prednisone. With respect to long-term benefit, improvement usually occurs within 1 month, reaching a maximum at 6 and then leveling off for the duration of treatment; in some patients, the benefit may wane after an initial satisfactory response in the first 4 to 6 months. In one third of those given methotrexate, treatment had to be discontinued because of adverse effects, less than 1% of which were life threatening. Careful baseline and follow-up monitoring is recommended until more data on the safety of methotrexate are available. |