Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 1681585 | [Treatment of rheumatoid spondylarthritis with salazosulfapyridine]. | 1991 Jul | Salazosulfapyridine (salazopyrin) (SASP) is effective basic treatment for rheumatoid arthritis (RA) after failure or intolerance of antimalarials or gold salts. Sulfapyridine is the active part of the molecule. Its mechanism of action probably involves anti-inflammatory activity as well as effects on cells participating in immune reactions. Adverse reactions occur in approximately one third of cases, in the majority of instances during the first three months of treatments. Simple digestive upsets are the commonest, but SASP may be responsible for sometimes severe cutaneous, hematological and hepatic reactions. The sometimes delayed onset of intolerance reactions justifies continuous monitoring of laboratory parameters. Results obtained with SASP are sometimes prolonged and therapeutic maintenance rates are similar to those seen with other basic treatment for RA. The use of SASP in RA should be tried before methotrexate in relatively early forms of the disease. | |
| 2802369 | Methotrexate-induced pneumonitis: appearance four weeks after discontinuation of treatment | 1989 Oct | A 71-year-old man with a long-standing history of rheumatoid arthritis required methotrexate treatment since 1986, with a total dose of 210 mg. In April 1987, before arthroplastic surgery, methotrexate was discontinued. Four weeks later a syndrome of fever, dry cough, shortness of breath, and diffuse air-space consolidations on the chest radiograph evolved. An antibiotic therapy had no beneficial effect, and a bronchoscopy yielded no pathogens. An open lung biopsy led to the diagnosis of methotrexate-induced pneumonitis. This is the first report of a case where methotrexate-induced pneumonitis developed several weeks after cessation of the treatment. Methotrexate can cause four types of pulmonary adverse reactions: pneumonitis, pulmonary edema, pulmonary fibrosis, and pleuritis. Possible pathogenetic mechanisms, symptoms, treatment, and prognosis are discussed. | |
| 3760277 | Oral methotrexate therapy for chronic rheumatoid arthritis ulcerations. | 1986 Sep | Eight patients with long-standing rheumatoid arthritis and cutaneous vasculitis ulcerations resistant to conventional therapy were treated successfully with a low-dose intermittent regimen of oral methotrexate. Objective clinical response was prompt and complete resolution was observed at about 12 weeks of therapy. The drug was well tolerated. Mild gastrointestinal side effects were the most common untoward reaction. We conclude that methotrexate therapy is an effective agent for some of the extraarticular manifestations of rheumatoid arthritis including vasculitis, and further clinical evaluation should be a consideration. | |
| 1775874 | [Lung diseases and treatment with methotrexate in rheumatoid arthritis]. | 1991 | Methotrexate (MTX) is used as sequential treatment of rheumatoid arthritis in doses ranging from 5 to 20 mg per week, but its effectiveness is impaired by undesirable and sometimes severe side-effects, notably on the lungs. We report three cases of lung disease in patients with rheumatoid arthritis under MTX therapy. Two patients had a lung infection caused by Escherichia coli and Pneumocystis carinii respectively and the third patient was a case of fatal pneumonia imputed to MTX. The signs and symptoms of these acute infectious or iatrogenic lung diseases are not specific. Bronchial endoscopy with bronchoalveolar lavage usually leads to a diagnostic of opportunistic infection, but it may also show an isolated excess, in both number and percentage, of alveolar leucocytes, pointing to a drug-induced pneumopathy. Acute respiratory failure due to MTX-induced pneumonia is not uncommon. It rapidly regresses either spontaneously or under corticosteroid therapy, but a number of deaths, as in our last patient, have been reported. The occurrence of these lung diseases is unrelated to the total dose of MTX. Reintroducing MTX does not mean that the condition will necessarily recur, but this can only be done in the absence of any other possible treatment. | |
| 1920333 | Should methotrexate be discontinued before elective orthopedic surgery in patients with rh | 1991 Jul | To determine if methotrexate (MTX) contributes to early postoperative complications, we studied 38 patients with rheumatoid arthritis (RA) who underwent elective orthopedic surgery. There were 4 complications of prosthetic joint infection or wound dehiscence or infection among 19 procedures performed on patients who continued MTX until less than 4 weeks before surgery, compared to no complications among 34 procedures performed on patients who discontinued MTX 4 weeks before surgery or who were taking no remittive agent for 3 months before surgery (p less than 0.03, Fisher's exact, 2-tailed). No demographic, clinical, laboratory, nutritional, or intraoperative differences between the 2 groups were apparent, suggesting that MTX may play a role in early postoperative complications in patients with RA. A larger, prospective trial to study this issue is warranted. | |
| 3534800 | Methotrexate in rheumatoid arthritis: an update. | 1986 Jul | Methotrexate, a folic acid antagonist, is being employed more frequently in an attempt to control rheumatoid arthritis that has not responded adequately to conventional therapies. Systemic administration of 7.5-15 mg weekly in a pulse fashion appears to be effective without precipitating serious adverse effects. Concern over potentially serious adverse effects and lack of well-controlled clinical trials have limited its use to severe, refractory disease. Its use in the future is likely to increase in these patients because of its ease of administration and the high response rate noted in clinical studies. | |
| 2242059 | Aspirin, hydroxychloroquine, and hepatic enzyme abnormalities with methotrexate in rheumat | 1990 Nov | Levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in patients with rheumatoid arthritis from 5 centers involved in the Arthritis, Rheumatism, and Aging Medical Information System were correlated with the use of specific antirheumatic medications. Elevated levels of SGOT and SGPT were most frequent in patients taking salicylates and methotrexate (MTX) and least frequent in patients taking hydroxychloroquine. The combination of MTX and salicylates greatly increased the frequency of abnormal liver enzyme values. In contrast, the addition of hydroxychloroquine to a regimen of either MTX or aspirin essentially eliminated the SGOT and SGPT abnormalities. Results from all 5 centers were consistent and remained so after adjustment for age, sex, and disease duration. Knowledge of these important drug interactions may permit continuation of MTX therapy in patients in whom the drug might otherwise be discontinued. | |
| 1896782 | [Treatment of rheumatoid polyarthritis with methotrexate]. | 1991 Jun | This retrospective study involved 60 patients (7 men, 53 women) with rheumatoid arthritis (RA) and given methotrexate between 1985 and 1990. The mean time that RA had been present was 12 years and more than half of the patients had received more than 3 types of general treatment in the past. The mean total duration of MTX was 17.3 months, with a total dose of 790 mg. The efficacy of MTX was confirmed by a significant improvement in clinical and laboratory parameters. Treatment was withdrawn permanently in 21 cases (35% of patients). Adverse reactions, responsible for two thirds of treatment withdrawals (14/21) occurred in most instances during the first year of treatment. Hepatic toxicity was commonest. Two cases of aplasia were reported as well as 3 cases of pneumonitis, one fatal. These involved two cases of secondary infection and one of pneumonitis directly imputable to MTX. Withdrawals for inefficacy were rare, occurring in less than 10 p. cent of patients. Treatment continuation rates were 77 p. cent at 1 year, 66 p. cent at 18 months, 55 p. cent at 2 years, 42 p. cent at 3 years and 32 p. cent at 4 years. MTX is effective treatment for RA but is not free of adverse reactions, sometimes potentially fatal. Prolonged monitoring is necessary because of the sometimes delayed onset of adverse reactions. | |
| 3529375 | Low-dose methotrexate in rheumatoid arthritis: effect and tolerance. An open trial and a d | 1986 | Weekly low-dose Mtx may be considered the preferred drug for the treatment of patients with severe, progressive RA resistant to conventional therapy. The drug is sufficiently safe, provided contra-indications are considered and treatment is carefully supervised. Controlled long-term prospective studies are needed in order to determine whether the drug demonstrably retards progression of the erosions, and to guard against untoward long-term adverse reactions. | |
| 3629206 | Hepatotoxicity associated with low-dose, long-term methotrexate treatment of rheumatoid ar | 1987 | Liver biopsies were performed in 17 patients with therapy-refractory rheumatoid arthritis who were treated successfully with 5-15 mg/week methotrexate (mtx). The average duration of exposure to mtx therapy for each patient was 2.8 years (range 1.5-5 years). Total cumulative mtx doses ranged between 633 and 1,655 mg (mean 1,060 mg). The biopsies revealed 16 cases of normal histology, of which 3 showed nuclear variability in the hepatocytes; 4 with mild fatty infiltration, 2 with mild fatty infiltration and portal round cell infiltration. Portal fibrosis was found in one patient who had psoriasis in addition to clinical RA. | |
| 2348423 | Treatment of rheumatoid arthritis with higher dose intravenous methotrexate. | 1990 Apr | A pilot study evaluated intravenous methotrexate (MTX) (initial dose 40 mg/m2; final dose, 26 mg/m2), weekly for 12 weeks in 10 patients with rheumatoid arthritis who failed oral MTX. Statistically significant differences were noted for all the response variables examined: joint count (p = 0.0017), morning stiffness (p = 0.014), global assessment (patient, p = 0.0032, physician, p = 0.029), Arthritis Impact Measurement Scale (p = 0.0004), erythrocyte sedimentation rate (p = 0.012), grip strength (right p = 0.044, left p = 0.011). All 7 patients who completed the 12-week treatment period fulfilled the predetermined criteria for response. Intravenous MTX at these doses has potential efficacy in this patient group. | |
| 2735960 | Methotrexate in rheumatoid arthritis. Toxic effects as the major factor in limiting long-t | 1989 Jun | In an effort to understand the prognostic features that may influence the probability of a patient's continuing to take methotrexate (MTX) over time, we studied 152 rheumatoid arthritis patients treated with MTX between 1981 and 1986. The overall probability of continuing to take MTX was 71.2% at 1 year, 55.5% at 3 years, 50% at 5 years, and 49% at 6 years. By univariate analysis, patients who started MTX therapy later in the study, American blacks, younger patients, those with less severe disease, and those with less frequent or less severe toxic events appeared to have a better probability of continuing the drug therapy. When these parameters were evaluated by multivariate analysis, only the time when MTX was started and the occurrence of toxic effects independently influenced the probability of continuing MTX. Thus, by current practice standards, toxic effects emerge as the main reason for MTX discontinuation. | |
| 3175573 | [Low-dose oral methotrexate in the treatment of rheumatoid polyarthritis]. | 1988 Sep 10 | 28 patients with severe rheumatoid arthritis were treated with pulse weekly oral methotrexate over a mean follow-up of 24 months (6-36 months). Within one month the patients improved significantly by all clinical standards of efficacy and erythrocyte sedimentation rate. Maximum improvement tended to occur after 6 months' therapy and was maintained for up to 36 months in most patients. 11 patients discontinued treatment because of adverse effects. It is concluded that this trial confirms the efficacy of methotrexate in rheumatoid arthritis. Careful baseline and follow-up monitoring is recommended due to frequent adverse reactions. | |
| 1941818 | Complications of immunosuppression associated with weekly low dose methotrexate. | 1991 Aug | Complications of immunosuppression are thought to be rare with the use of low dose pulse methotrexate (MTX) for nonneoplastic conditions. We describe 4 complications of immunosuppression observed in a group of 41 patients who had received MTX for at least 6 months, during a 2-year period. We report the first case of a reversible lymphoproliferative disorder similar to that reported with immunosuppressive therapy associated with organ transplantation. Two cases of disseminated herpes zoster and 1 case with Pneumocystis carinii pneumonia are described. As the indications for the use of low dose MTX broaden and older patients with other comorbid diseases are included, our experience suggests that complications of immunosuppression with prolonged use of MTX may be seen more commonly. | |
| 2406713 | Rheumatoid arthritis. Practical use of medications. | 1990 Feb 15 | The treatment of rheumatoid arthritis is undergoing steady change as new medications are approved and new regimens are attempted. Once the diagnosis is ensured, therapy should include appropriate rest, physical and occupational therapy, involvement of the family or a supportive caregiver, and, most important, participation of the patient. If the disease is not terribly aggressive, therapy with nonsteroidal anti-inflammatory drugs is appropriate initially. If no response is obtained within 2 to 3 weeks, a new dose or different nonsteroidal agent is recommended. In many patients, aspirin, particularly if enteric-coated, is successful and very cost-effective. Disease-modifying antirheumatic drugs (DMARDs) are sometimes being used earlier in disease than previously. Hydroxychloroquine sulfate (Plaquenil Sulfate), auranofin (Ridaura), or sulfasalazine (Azulfidine, S.A.S.-500) is sometimes effective for early rheumatoid arthritis. For patients with more aggressive disease, intramuscular gold is the drug of first choice, and it is the only one that has been shown to decrease the rate of formation of new erosions. Significant toxic reactions occur in 30% to 40% of patients, however. D-penicillamine (Cuprimine, Depen) and azathioprine (Imuran) can be used if intramuscular gold is unsuccessful. Methotrexate (Rheumatrex Dose Pack) is the newest DMARD approved for treatment of rheumatoid arthritis. Its onset of action is rapid, and it is an effective anti-inflammatory agent. Its toxicity in patients with rheumatoid arthritis is not yet fully understood, however. Combination therapy with DMARDs is in its infancy, but such treatment is likely to become more prevalent in the future. | |
| 2762663 | Intrarticular methotrexate in the therapy of rheumatoid arthritis. | 1989 May | 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. | |
| 1679342 | Disease-modifying antirheumatic drugs: gold, penicillamine, antimalarials, and sulfasalazi | 1991 Jun | In the assessment of the effects of disease-modifying antirheumatic drugs, three or four clinical measurements supported by the erythrocyte sedimentation rate, and sometimes radiographs, are generally agreed to be correct. Some advocate functional assessments also, or even alternatively. Several studies compared gold, penicillamine, antimalarials, and sulfasalazine either with each other or with placebo, and occasionally with methotrexate. No important differences between the general performance of the four drugs were found. More work was reported on sulfasalazine than on the other three drugs; the data support that it has a place in our armamentarium. Several important contributions concerned strategies of treatment. It is considered that disease-modifying antirheumatic drugs should be used earlier and more aggressively in rheumatoid arthritis. This aspect was perhaps the key note of the 1990 literature on this topic. As part of the new strategies, combination therapy is urged by some rheumatologists, whereas others urge caution on the grounds that we do not yet know enough about the effects of combinations, or by how much the risks of adverse effects are increased in combination. | |
| 2225450 | Parenteral nitrogen mustard for inflammatory arthritis. | 1990 Oct | A patient with progressive psoriatic arthritis refractory to methotrexate therapy was treated empirically with intravenous nitrogen mustard, or HN2. His response to therapy was compared with the responses of five rheumatoid arthritis patients treated with the same regimen. At 14 days after therapy was begun the patient with psoriatic arthritis showed significant improvement, at least comparable to that observed in the rheumatoid arthritis group. Intravenous HN2 therapy may be an alternative to methotrexate for progressive psoriatic arthritis. | |
| 3041245 | Hepatotoxicity of methotrexate in rheumatic diseases. | 1988 May | Methotrexate-induced hepatotoxicity is well recognised in the treatment of leukaemia, psoriasis and rheumatoid arthritis. The pathological lesions are non-specific, consisting of fatty change, nuclear pleomorphism, hepatocyte necrosis, portal chronic inflammatory infiltrate, fibrosis and cirrhosis. The mechanism of liver injury is poorly understood; intracellular accumulation of methotrexate polyglutamate and consequent folate depletion are suspected to play a role. Early studies in psoriasis clearly established a relationship of the hepatic injury with the frequency of methotrexate administration. With weekly low dose therapy, however, consensus is lacking regarding the incidence of hepatotoxicity because studies have had disparate control groups, used variable dosage regimens and often failed to document pre-existing liver disease or categorised patients at risk, i.e. elderly patients, alcoholics and obese diabetics. Moreover, current methods of assessing the degree of hepatic injury are subjective, relying on interpretation by an experienced histopathologist. Preliminary evidence suggests less frequent and less severe hepatotoxicity occurs in patients with rheumatoid arthritis, probably as a result of lower methotrexate doses and better patient selection. Nevertheless, until the risk of serious liver disease is better defined it is recommended that patients have a pretreatment liver biopsy, a follow-up biopsy after a cumulative dose of 1500 mg, and then biopsies approximately every 2 years in the absence of other evidence of liver disease or risk factors. | |
| 2805607 | Low-dose methotrexate treatment of rheumatoid arthritis; long-term observation of efficacy | 1989 Sep | Forty-one patients with rheumatoid arthritis (RA) were treated with a weekly low-dose of methotrexate for a mean period of 32 months (range, 5-81 months) and were given a mean total dose of 954 mg (range, 145-2000 mg). Eighty-three percent of the patients improved. Of these 39% (16 patients) had a complete clinical remission and 17% (7 patients) showed marked improvement, 27% (11 patients) showed moderate improvement and 17% (7 patients) were unchanged. Patients responding to methotrexate therapy maintained the improvement as long as the therapy continued, unless severe infections occurred. Seven patients withdrew during the study including two, who died of myocardial infarction. Methotrexate was withdrawn because of adverse drug reactions in two patients, fear of toxicity in two and for administrative reasons in one patient. Adverse reactions developed in 25 patients (61%). In all but two cases these reactions were mild and reversible. Pancytopenia, a major side effect, was present in two patients: in one patient in association with pneumonia and in the other patient associated with an acute infectious enteritis (after three years treatment in the first and six years in the second patient); both recovered when methotrexate was discontinued. Age, sex, duration of treatment did not remarkably influence the outcome of therapy or the occurrence of adverse reactions. |