Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 7806117 | [Current status of basic antirheumatic therapy]. | 1994 Oct 30 | Basic treatment of inflammatory rheumatic diseases is effective, but not necessarily remission-inducing. Its mechanisms of action are only partly understood, and the reasons for the variations in response rate of between 40 and 80% are also unknown. The original concept of starting with the least toxic of these substances, and then only after the failure of treatment with non-steroidal anti-inflammatory drugs, has now been abandoned. Taking compliance as a measure of therapeutic value, among the most important of the substances employed, methotrexate is the most, oral gold the least, favorable, while azathioprine, sulfasalazine, antimalarial agents and D-penicillamine do not differ significantly from another. | |
| 8949606 | [Pancytopenia in rheumatoid arthritis treated with methotrexate]. | 1996 Sep 7 | OBJECTIVES: Six cases of pancytopenia were analyzed retrospectively among 350 patients with rheumatoid arthritis treated with methotrexate. Pancytopenia is an uncommon but severe secondary effect of methotrexate. CASE REPORTS: Five patients were hospitalized for infectious complications or hemorrhage with favorable outcome. One patient died due to septic shock. There were risk factors in all 6 patients: 5 were over 65 years of age, creatinine clearance was under 50 ml/min in 4, hypoalbuminemia was found in 4 and methotrexate was combined with an antiinflammatory drug in 4 and with ranitidine in 2. The pharmacological imputability of methotrexate was probable in 4 of the 6 patients. DISCUSSION: Acute pancytopenia in patients treated with methotrexate can be prevented by recognizing risk factors, regular laboratory tests and supplementation of all patients with folic acid according to protocols to be established. | |
| 8124920 | Concurrent acute megaloblastic anaemia and pneumonitis: a severe side-effect of low-dose m | 1993 Dec | In a patient suffering from rheumatoid arthritis, we report the first simultaneous occurrence of two side effects of low-dose methotrexate: an acute megaloblastic anaemia and a pneumonitis. A combination of methotrexate suspension, folinic acid and corticosteroids led to recovery. The correlation between the haematologic and pneumologic toxicity is discussed. | |
| 7738941 | The effect of age and renal function on the efficacy and toxicity of methotrexate in rheum | 1995 Feb | OBJECTIVE: To evaluate whether age and renal impairment affect the rate of side effects or expected efficacy of methotrexate (MTX) in rheumatoid arthritis (RA). METHODS: Data was pooled from 11 MTX clinical trials containing 496 patients treated with MTX. We evaluated those patients less than 60 years old and those in 5-year groupings of age over age 60. Using serum creatinine, weight, and age, we calculated creatinine clearance and placed patients into quartiles based on their baseline creatinine clearance. To evaluate efficacy, we used changes in American College of Rheumatology core set efficacy measures available in these trials. To quantify side effects, we scored each side effect based on a modified Fries toxicity score and assigned each patient a score based on the worst side effect experienced during the trial. We also separately evaluated liver toxicities (twice normal elevation of AST or ALT), respiratory toxicity and severe toxicities. Intent-to-treat analyses were performed, adjusting for study of origin. Results were confirmed by placebo controlled trials, comparing MTX and placebo treated patients. RESULTS: Neither age nor renal impairment had any effect on the efficacy of MTX. Those in the oldest age groups (65-69 years, > or = 70 years) were not at higher risk of side effects from MTX. However, patients with renal impairment had a higher overall rate of toxicity and were at higher risk of severe and respiratory toxicities than those whose creatinine clearances were at least 99.8 ml/min (reference group). The odds of severe toxicity were increased roughly 4-fold in those with renal impairment. CONCLUSION: Among clinical trial patients, age does not affect MTX efficacy or the rate of side effects. Renal impairment, however, increases the risk of side effects. | |
| 7481247 | [Methotrexate treatment in non-cancerous disorders]. | 1995 Jul | Weekly administration of low doses methotrexate (7.5 mg to 25 mg a week) is considered as one of the most important progresses in the management of rheumatoid arthritis. Its efficacy has also been demonstrated for the treatment of other inflammatory processes such as psoriasis arthritis and, more recently, Crohn's disease. We here review the indications, the limits and the side effects of such therapeutic approach in various inflammatory and/or autoimmune diseases. | |
| 1433018 | Massive intrahepatic hemorrhage following routine liver biopsy in a patient with rheumatoi | 1992 Sep | Massive intrahepatic hemorrhage occurred in a patient with rheumatoid arthritis (RA) after a routine liver biopsy done to assess possible methotrexate (MTX) hepatotoxicity. Major complications of liver biopsy occur about once in every 600 biopsies, and mortality from liver biopsy has been reported. Life threatening hepatic toxicity occurs rarely during low dose MTX administration, and it is unclear whether routine liver biopsies identify patients at high risk for these complications. Until the relative risks of liver biopsy and serious MTX liver toxicity are better defined, the use of routine liver biopsies should be recommended only after careful consideration of potential procedural complications in patients with RA treated with MTX. | |
| 8765212 | DNA hypomethylation in inflammatory arthritis: reversal with methotrexate. | 1996 Aug | This study investigated whether methotrexate, by interrupting the methyl transfer function of folate, can induce genomic DNA hypomethylation in patients with inflammatory arthritis. Consecutive subjects with inflammatory arthritis (rheumatoid or psoriatic), who were taking methotrexate (n = 7) or other medications (n = 6), and control subjects, either healthy or with osteoarthritis and taking nonsteroidal anti-inflammatory agents only (n = 9) were recruited. The methylation status of genomic DNA from peripheral blood mononuclear cells was determined. Plasma levels of folate, B12, and pyridoxal-5'-phosphate (PLP), all of which are involved in biologic methylation, were also examined. The extent of genomic DNA methylation was lowest in subjects with inflammatory arthritis who were not taking methotrexate, highest in subjects with inflammatory arthritis who were taking methotrexate, and intermediate in control subjects (p < 0.05). Plasma levels of folate and B12 were similar among the three groups. The mean plasma PLP level in subjects with inflammatory arthritis was 33% lower than that in control subjects (p = 0.04). No significant correlation between genomic DNA methylation and folate, B12, and PLP levels was observed. These data do not support the hypothesis that methotrexate induces genomic DNA hypomethylation. However, these data indicate that inflammatory arthritis is associated with genomic DNA hypomethylation that is reversed with methotrexate. Future studies using a larger number of subjects are warranted to confirm these findings. | |
| 8604723 | Management of osteoarthritis and rheumatoid arthritis: prospects and possibilities. | 1996 Feb 26 | Conventional drug therapy in rheumatoid arthritis (RA) has failed to control the longterm morbidity and mortality associated with RA. Similarly, drug therapy for osteoarthritis (OA) can relieve symptoms, but it is not clear that it alters progression of disease. Three classes of drugs are widely used for treatment of RA: nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and the slow-acting agents. In most patients, pharmacologic therapy is initiated with NSAIDs. These drugs can relieve symptoms but do not alter the course of the disease. The gastrointestinal and other side effects attributed to these compounds are well known. Similarly, use of corticosteroids can provide rapid pain relief to patients with RA and, if used in low doses, pose limited risk of toxicity. Slow-acting agents, including gold, d-penicillamine, and methotrexate, appear to decrease radiographic progression and improve clinical and biochemical indicators of RA. Therefore, newer treatment philosophies encourage use of slow-acting agents earlier in the course of the disease in order to prevent or diminish bone and joint erosions and destruction and other manifestations of disease progression. Drugs under investigation for the treatment of arthritis appear to exhibit disease-modifying or immunomodulating properties. Tenidap is a novel agent that possesses a dual mechanism of action: cyclooxygenase inhibition and modulation of cytokine activity. In addition, several biologic agents, including antibodies to tumor necrosis factor-alpha (TNF-alpha) and to intercellular adhesion molecule-1, may prove useful. These immunotherapeutic strategies are based on knowledge of the role of cytokines in the inflammatory process in arthritis. Osteoarthritis may be managed using drug and nondrug modalities. Weight loss is especially important when OA is in the weight-bearing joints. Biopsies of synovium from patients with OA show evidence of inflammation, but whether this disease should be treated with analgesics alone or with anti-inflammatory drugs remains controversial. Other treatment modalities, including tissue transplants and cytokine-modulating drugs, are emerging for the potential therapy of OA. Surgery may also be appropriate if drug treatment fails to control symptoms. | |
| 7973475 | Combination therapy with methotrexate and chloroquine in rheumatoid arthritis. A multicent | 1994 | To compare the efficacy of the combination therapy Methotrexate (MTX) and Chloroquine (CHLO) with MTX and Placebo (PLA) in the treatment of Rheumatoid Arthritis. A total of 82 patients with Rheumatoid Arthritis (RA), diagnosed according to the American College of Rheumatology criteria, received orally either MTX 7.5 mg/week and CHLO 250 mg/day or MTX 7.5 mg/week and PLA 1 tablet/day. Adverse effects (AE) were monitored monthly and disease activity was assessed at 0, 2, 4 and 6 months. Sixty-eight patients completed the study. All outcome measures improved significantly in both treatment groups. Patients receiving MTX/CHLO ended the study with a significantly lower joint count, greater grip strength and better functional ability the patients in the MTX/PLA group, respectively; 4.5 vs 7.5 (P < 0.05), 113.3 vs 89.1 (P < 0.05) and 0.636 vs 0.811 (P < 0.05). Mild AE were more frequently observed in the MTX/CHLO, 17 events in 15 patients, compared to 9 events in 8 patients in the MTX/PLA group (NS). These data indicate that MTX/CHLO is slightly more efficacious and toxic than is MTX/PLA in the treatment of RA. | |
| 7683881 | Effects of administration of an anti-CD5 plus immunoconjugate in rheumatoid arthritis. Res | 1993 May | OBJECTIVE: To evaluate the safety and activity of an immunoconjugate of ricin A chain and anti-CD5 monoclonal antibody (anti-CD5 IC), with and without concomitant methotrexate and/or azathioprine, in the treatment of rheumatoid arthritis (RA). METHODS: Seventy-nine patients with active RA were enrolled in 2 prospective open-label protocols. RESULTS: Using composite criteria, response rates were 50-68% at 1 month and 22-25% at 6 months. Transient depletion of CD3/CD5 T cells was observed on days 2 and 5 of treatment, with reconstitution on day 15 or day 29. Treatment-associated adverse effects were common but resolved rapidly without sequelae. CONCLUSION: These findings suggest activity of anti-CD5 IC in active RA and warrant confirmation in a multicenter randomized study (currently underway). | |
| 8782127 | Lack of interaction between bromfenac and methotrexate in patients with rheumatoid arthrit | 1996 Jun | OBJECTIVE: To compare the pharmacokinetics of methotrexate (MTX) and bromfenac administered separately or coadministered in patients with rheumatoid arthritis (RA). METHODS: Patients received their usual weekly oral dose of MTX on Days 1 and 8 and bromfenac 50 mg every 8 h from Days 4 to 9. On Days 1 and 8 serial blood and urine samples were collected to study the pharmacokinetics of MTX and 7-hydroxymethotrexate (7-OHMTX). Bromfenac pharmacokinetics were studied on Days 7 and 8. Concentrations of the analytes were assayed using validated high performance liquid chromatography methods. RESULTS: Nine patients, 5 women and 4 men, completed the study. No statistically significant changes were observed in any of the pharmacokinetic variables evaluated for bromfenac with or without MTX. Bromfenac also did not alter the pharmacokinetics of low dose MTX. However, some significant changes were observed in the pharmacokinetics of 7-hydroxymethotrexate: a 30% increase in dose normalized area under the serum concentration time curve (mean +/- SD) to 3102 +/- 1397 micrograms.h/l and a 16% decrease in renal clearance to 10.0 +/- 6.7 ml/h/kg. Eight patients had mild or moderate adverse events: most were considered unrelated to the study drug by the investigator. One patient did not complete the study because of moderate hypertension. No patient had clinically important abnormal laboratory test results. CONCLUSION: No clinically significant changes in MTX pharmacokinetics were detected in patients with RA when bromfenac was added to MTX therapy. Although 7-OHMTX concentrations were elevated, the changes were small and unlikely to be of clinical significance. MTX did not alter the pharmacokinetics of bromfenac. | |
| 8833060 | Initial experience combining methotrexate with biologic agents for treating rheumatoid art | 1996 Mar | The combination of traditional disease modifying antirheumatic drugs such as methotrexate (MTX) with biologic agents for treating rheumatoid arthritis (RA) has thus far been limited. The combination of MTX and a depleting anti-CD4 monoclonal antibody (cM-T412) has been evaluated in phase I and II trials in patients with refractory RA. The potential of combining MTX with other biologic agents is reviewed. | |
| 1294735 | Longterm drug therapy for rheumatoid arthritis in seven rheumatology private practices: II | 1992 Dec | The probability of continuation of 1,077 courses of 2nd line drugs taken by 532 patients with rheumatoid arthritis treated in 7 rheumatology private practices was examined. This probability was that 50% of courses were continued over 10 months for oral gold, 20 months for hydroxychloroquine, 21 months for penicillamine, 25 months for parenteral gold, 27 months for azathioprine, and more than 60 months for methotrexate (MTX). MTX and prednisone were the only drugs continued by more than 50% of patients after 60 months, while about 20% of courses of other 2nd line drugs other than oral gold were estimated to be continued at 60 months. Estimated drug continuation did not differ significantly according to age, duration of disease, or whether the drug was the first, second, or 3rd 2nd line drug used. Some patients took each 2nd line drug for more than 5 years, suggesting a favorable experience, but most courses were not continued beyond 2 years. | |
| 7482063 | [Methotrexate and salazosulfapyridine in the long-term treatment of rheumatoid arthritis]. | 1995 Aug | Long term treatment of 190 cases of rheumatoid arthritis with either methotrexate or salazosulfapyridine was analyzed for their efficacy and adverse effects. Both treatment groups showed improvement of clinical symptoms, erythrocyte sedimentation rate, and CRP after 1 month of treatment, while RAHA titers decreased significantly after several months. Erythrocyte sedimentation rate and CRP of salazo-sulfapyridine group, once improved, deteriorated again after 12 months of treatment, while methotrexate group showed sustained improvement for 48 months. Radiologic progression estimated according to JF Fries was significantly less in MTX group than in SASP group. Life table analysis showed that the overall probability of continuing methotrexate or salazosulfapyridine at 4 years was 63% and 55%, respectively. The main reason of treatment termination in methotrexate group was adverse effects, while that in salazo-sulfapyridine group was inefficacy. | |
| 7586777 | Folic acid and cyanocobalamin levels in serum and erythrocytes during low-dose methotrexat | 1995 Jul | OBJECTIVE: To compare folic acid (FA) levels in patients being treated with methotrexate (MTX) with those of untreated patients in order to investigate potential folate depletion by MTX and its possible relationship to the drug's efficacy. METHODS: In 33 patients on low-dose MTX therapy and in 24 controls, FA and cyanocobalamin (B12) levels were determined in serum and red blood cells (RBC). In addition, MTX levels in the RBC and serum were measured, and clinical and laboratory measures of disease activity were evaluated. RESULTS: MTX treated patients had lower FA levels than controls (median 4.36 vs 7.37 ng/ml, p < 0.001). A significant correlation between serum FA and MTX/RBC (p < 0.01) and between the weekly dose and MTX/RBC (p < 0.01) was seen. There was apparently no correlation between FA and the cumulative total MTX. MTX patients had lower B12/RBC levels than the controls (p < 0.001); the serum levels of B12 were not different. Clinical features, ESR and CRP did not correlate with FA, B12 or MTX levels. CONCLUSIONS: The degree of folate depletion during MTX therapy depends primarily upon the weekly administered dose. Folate depletion may be related to B12 deficiency in RBC. Since FA levels were not related to parameters of disease activity it is conceivable that MTX does not exert its action in RA primarily by inhibiting dihydrofolatereductase. Therefore, additional folate compounds, if necessary, should not lead to a reduction in the efficacy of MTX. | |
| 8849378 | Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis. | 1996 Feb | OBJECTIVE: To assess the frequency of methotrexate (MTX)-induced pancytopenia in rheumatoid arthritis (RA). METHODS: A MEDLINE literature search was conducted to identify articles published during the last 15 years (1980-1995) that presented data on MTX-associated pancytopenia. Two case reports of our own experience are also presented. In addition, articles that examined risk factors associated with MTX-related pancytopenia were identified. RESULTS: A total of 70 patients with pancytopenia related to MTX therapy were identified (68 reported in the literature, 2 from our own experience). Sixty-one of the patients were described in published case reports, 7 patients were from 5 long-term prospective studies. In many of these cases, predisposing factors for the development of pancytopenia were described. The 5 long-term prospective studies reported toxicity data on patients who had been treated with MTX for at least 13 weeks. A total of 511 patients were included in the prospective trials, yielding an overall incidence of pancytopenia of 1.4% (7 of 511). Of the 70 cases reported, 12 patients died (17%). Most of them had impaired renal function, hypoalbuminemia, concurrent infection, and/or concomitant medication with more than 5 drugs. The minimal cumulative MTX dose leading to fatal pancytopenia was 10 mg, observed in one of our patients. CONCLUSION: Pancytopenia is not an uncommon side effect of low-dose pulse MTX therapy in RA. It can lead to serious complications, including death. | |
| 8278819 | Comparing the strengths and weaknesses of observational and experimental studies using a p | 1993 Oct | A recent prospective, observational study in rheumatoid arthritis patients indicated that the addition of hydroxychloroquine to either aspirin or methotrexate therapy decreased the incidence of hepatic enzyme abnormalities. This interesting finding is of potential clinical importance, but its validity needs to be examined in terms of the potential confounders inherent in observational studies. Although one of the study's strengths is its derivation from "real-life" data, some potential confounders that might weaken the data include a need to examine whether any scientific rationale can be discerned for the observation; examination of control-case matching (issues of randomization and baseline disease characteristics); the potential for attribution bias; data-collection methods (prospective versus retrospective, uniform versus chart review); and equivalency of treatment protocols, dosing regimens, and concomitant medications. Potential scientific rationale exists for the observed interaction, and data collection is both uniform and prospective. These strengths are confounded by the inevitable lack of randomization in observational studies, the potential for differences in baseline disease characteristics, attribution bias, a lack of controlled dosing regimens and treatment protocols, and an assumption that all nonsteroid antiinflammatory drugs are alike (which is not true). On balance, the hypothesis generated by these data is compelling enough to deserve further testing in both observational and experimental settings. | |
| 7827378 | Recovery from rheumatoid cerebral vasculitis by low-dose methotrexate. | 1994 Oct | We report the successful management of cerebral vasculitis in a 46-year-old woman with longstanding rheumatoid arthritis with low-dose methotrexate. She suddenly developed dysarthria and left hemiparesis. Magnetic resonance imaging disclosed ischemia of the right pons, and angiography demonstrated cerebral vasculitis of vertebro-basilar arteries. The vasculitis was refractory with high-dose steroid therapy, which had only transient clinical benefit, and evolution to the pontine infarction followed. Her clinical status showed marked improvement in association with recovery of the vascular abnormalities after the initiation of the methotrexate therapy. | |
| 7791814 | Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. The | 1995 Jul 20 | BACKGROUND: Patients with severe rheumatoid arthritis who are treated with methotrexate frequently have only partial improvement. METHODS: In a six-month randomized, double-blind trial, we compared combination therapy with cyclosporine (2.5 to 5 mg per kilogram of body weight per day in two divided doses at 12-hour intervals) and methotrexate (at the maximal tolerated dose) with methotrexate and placebo in 148 patients with rheumatoid arthritis who had residual inflammation and disability despite partial but substantial responses to prior methotrexate treatment. The primary outcome measure was the change in the number of tender joints. RESULTS: The mean (+/- SD) dose of cyclosporine at the final treatment was 2.97 +/- 1.02 mg per kilogram per day. As compared with the placebo group, the patients in the treatment group had a net improvement in the tender-joint count of 25 percent, or 4.8 joints (95 percent confidence interval, 0.7 to 8.9; P = 0.02), and in the swollen-joint count of 25 percent, or 3.8 joints (95 percent confidence interval, 1.3 to 6.3; P = 0.005); improvement in overall disease activity as assessed by the physician (19 percent, P < 0.001) and the patient (21 percent, P < 0.001); and improvement in joint pain (23 percent, P = 0.04) and in the degree of disability (26 percent, P < 0.001). The mean erythrocyte sedimentation rate increased by 4.2 mm per hour in the cyclosporine group and decreased by 4.8 mm per hour in the placebo group (P = 0.006). Thirty-six patients (48 percent) in the cyclosporine group and 12 patients (16 percent) in the placebo group (P < 0.001) met the 1993 criteria for improvement of the American College of Rheumatology (more than 20 percent improvement in the numbers of both swollen and tender joints and improvement in three of five other variables). Seventeen patients in the cyclosporine group and 12 patients in the placebo group were withdrawn from the study; 2 patients in the cyclosporine group died, 1 from viral pneumonia and the other in a motor vehicle accident. Serum creatinine concentrations increased by a mean of 0.14 +/- 0.27 mg per deciliter (12 +/- 24 mmol per liter) in the cyclosporine group and by 0.05 +/- 0.19 mg per deciliter (4 +/- 17 mmol per liter) in the placebo group (P = 0.02). CONCLUSIONS: In a six-month study, patients with severe rheumatoid arthritis and only partial responses to methotrexate had clinically important improvement after combination therapy with cyclosporine and methotrexate. Side effects were not substantially increased. Long-term follow-up of patients treated with this combination is needed. | |
| 8103964 | Variability in individual responses of 532 patients with rheumatoid arthritis to first-lin | 1993 | Variability in individual responses to drugs used to treat rheumatoid arthritis was studied in 532 patients under care in seven U.S. rheumatology private practices. Among 15 nonsteroidal anti-inflammatory drugs (NSAIDs), estimated continuation of 1,775 courses was 48% at 12 months and 20% at 60 months. Acetylated salicylates, other than plain aspirin, were continued significantly longer than other NSAIDs. Among second-line drugs, estimated continuation of 50% of courses was 10 months for oral gold, 20 months for hydroxychloroquine, 21 months for penicillamine, 25 months for parenteral gold, 27 months for azathioprine, and more than 60 months for methotrexate and prednisone, the only drugs continued by more than 50% of patients 60 months after initiation. |