Methotrexate In Treatment Of Rheumatoid Arthritis Research Articles

Effects of long-term administration of methotrexate on bone mineral density in rheumatoid arthritis.

Because previous studies of high-dose methotrexate usage have demonstrated an effect on bone formation and resorption, this study was done to determine whether long-term, low-dose use of methotrexate for the treatment of rheumatoid arthritis causes bone loss. Bone mineral density (BMD) of the lumbar spine and hip was measured in 10 Caucasian postmenopausal women who had never received methotrexate and 10 Caucasian postmenopausal women who had received the drug for 3 or more years. There were no significant differences in BMD at the lumbar spine (L2-L4) between patients who had used long-term methotrexate compared with patients never treated with methotrexate (1.08 +/- 0.08 g/cm2 versus 0.98 +/- 0.14 g/cm2, respectively; P = 0.08). Similarly, there were no significant differences in BMD at the femoral neck between methotrexate users and nonusers (0.81 +/- 0.08 g/cm2 versus 0.76 +/- 0.15 g/cm2, respectively; P = 0.42). These results suggest that long-term low-dose methotrexate treatment for rheumatoid arthritis is not associated with accelerated bone loss.

Bronchoalveolar lavage cell profile in methotrexate induced pneumonitis.

BACKGROUND: Pneumonitis is a rare but potentially life threatening side effect of methotrexate treatment for rheumatoid arthritis which needs to be distinguished from interstitial lung disease due to rheumatoid arthritis....

Liver cirrhosis due to methotrexate in a patient with rheumatoid arthritis

A 49-year-old female with rheumatoid arthritis developed liver cirrhosis after a cumulative dosage of 6 g methotrexate (MTX). There were mild liver enzyme abnormalities, decreased liver synthesis function and possible signs of portal hypertension. After stopping MTX all laboratory abnormalities disappeared except for a mild thrombocytopenia. Risk factors and guidelines for monitoring liver toxicity during MTX treatment in rheumatoid arthritis are discussed.

Prognostic factors for the outcome of methotrexate treatment in rheumatoid arthritis.

Aim of the study: To evaluate various symptoms/findings for their ability as prognostic markers in MTX-therapy in patients with rheumatoid arthritis.

Usefulness of the American College of Rheumatology recommendations for liver biopsy in methotrexate-treated rheumatoid arthritis patients.

To test the usefulness and cost savings resulting from application of the new American College of Rheumatology (ACR) guidelines for assessing the risk for the development of clinically significant liver disease in rheumatoid arthritis (RA) patients treated with methotrexate (MTX). One-hundred twelve MTX-treated RA patients were prospectively followed up for MTX hepatotoxicity and underwent liver biopsies according to modified guidelines of the Psoriatic Task Force (PTF). All biopsies were graded according to the Roenigk classification. The new ACR recommendations were then retrospectively applied to test their usefulness and cost-effectiveness in this cohort. Based on the PTF guidelines, 66 patients underwent liver biopsies; a total of 110 liver biopsies were performed. Two patients had biopsy-related complications. Five patients were found to have Roenigk grade IIIB or IV histologic abnormalities. The total cost for this group was $111,380. Applying the new ACR criteria, only 15 patients would have undergone liver biopsies; there would have been a total of 18 biopsies, with no complications. Four of the 5 patients with Roenigk grade IIIB or IV liver abnormalities would have been identified. One patient with insulin-dependent diabetes mellitus (IDDM) who was found to have cirrhosis (Roenigk grade IV) on liver biopsy as a result of use of the PTF guidelines would have been missed with use of the ACR guidelines. The total cost for the group receiving biopsies based on the ACR guidelines would have been $16,956. Overall, the new ACR guidelines had 80% sensitivity and 82% specificity and resulted in a cost savings of $1,430 per patient. The new ACR guidelines on MTX monitoring and biopsy surveillance appear to be clinically useful and result in considerable cost savings. However, 1 IDDM patient with significant liver histologic abnormalities would have been missed. We suggest that IDDM be added to the ACR guidelines as a risk factor for MTX hepatotoxicity.

Infections during low-dose methotrexate treatmentin rheumatoid arthritis

We studied the infection rate in patients with rheumatoid arthritis (RA) treatedwith low-dose methotrexate (MTX) in a 6-year open prospective study and in a 12-month randomized double blind trial comparing MTX with azathioprine (AZA) that was followed by a 3-year open prospective study. The literature on infections during low dose MTX in RA was reviewed. We also did a search for therapy-related opportunistic infections in RA and in MTX-treated psoriasis and psoriatic arthropathy patients. In our studies the infection rate during MTX treatment was higher in severe RA than in moderate RA. In severe RA there were often 2 infections simultaneously. The majority of the infections occurred in the first 1.5 years of treatment. There was no difference in the infection rate of MTX and AZA in the comparative trial. In the literature the infection rate was highest in short-term double-blind studies. Opportunistic infections are increasingly reported in RA treated with MTX and rarely with AZA, cyclosporine A, and cyclophosphamide or in MTX treated psoriasis and psoriatic arthropathy. In RA it appears that the initial period of treatment with MTX is the most vulnerable phase for infections, with the exception of opportunistic infections, which are not limited to a certain treatment period. Probably there are more MTX-associated infections in severe RA than in moderate RA.

New developments in drug hepatotoxicity

The spectrum of drug-related hepatotoxicity can range from sub-clinical liver disease with mildly abnormal liver enzyme tests to subfulminant and fulminant hepatic failure requiring liver transplantation. Many commonly used prescription and nonprescription drugs are known to have hepatotoxic side effects. In this review, only those medications that have received the most attention in the recent literature are discussed. Additionally, a number of the many herbal medicines and other alternative health agents commonly used in the United States that are now recognized as having unappreciated hepatotoxic potential are reviewed along with another over-the-counter medication, sustained-release niacin. The recently recognized hepatotoxicity of some of the newer antimicrobials is described as well as the newly identified hepatotoxic effects of other older antibiotics. Updated recommendations regarding methotrexate treatment of rheumatoid arthritis and the potential for liver disease are presented. Other commonly used drugs with possible hepatotoxic side effects are also discussed.

Interstitial pneumonia due to cytomegalovirus following low‐dose methotrexate treatment for rheumatoid arthritis

Interstitial pneumonia due to cytomegalovirus following low‐dose methotrexate treatment for rheumatoid arthritis

Methotrexate-related pulmonary complications in rheumatoid arthritis.

Methotrexate (MTX) was described as a drug in 1946' and first used in the treatment of human disease (childhood leukaemia) in 1948.2 Successful MTX treatment for rheumatoid arthritis (RA) and psoriasis was reported in 1951,3 although the interest in this drug at that time was probably overshadowed by the impressive results of cortico-steroid treatment until approximately 1980. MTX was approved by the food and drug administration (FDA) for the treatment of severe and disabling psoriasis in 1971 and for RA only in 1988.4 MTX-related pulmonary toxicity was first observed during treatment of childhood leukaemia in 19695 and later in malignancies, psoriasis6 7 and polymyositis.7 I Though it was postulated that pulmonary toxicity would appear only with a weekly dose higher than 20 mg,7 this did not prove to be true when in 1983 pneumonitis was also reported during low-dose MTX treatment for RA9 10

Postoperative results of rheumatoid arthritis patients on methotrexate at the time of reconstructive surgery of the hand.

We conducted a retrospective chart review examining the frequency of local postoperative infection and poor wound healing of 15 methotrexate-treated rheumatoid arthritis patients undergoing 155 procedures during 39 surgeries. The patients were compared to a group of rheumatoid patients not on methotrexate who underwent similar reconstructive surgery of the hand. The patients taking methotrexate were followed postoperatively for a minimum of 10 weeks, with a mean follow-up time of 1 year, 42 weeks. There were no postoperative complications that would lead to the belief that the administration of methotrexate results in poor wound healing or leaves the patient more susceptible to postoperative infection. Our findings and a review of the literature support a continuation of methotrexate therapy in rheumatoid arthritis patients scheduled for reconstructive surgery of the hand and wrist.

Herpes zoster in patients with rheumatoid arthritis treated with weekly, low-dose methotrexate

Herpes zoster occurred in nine patients with methotrexate-treated rheumatoid arthritis. We compared these patients to a large group of methotrexate-treated rheumatoid arthritis patients in order to uncover potential factors explaining the occurrence of herpes zoster. Data from 187 patients taking methotrexate were reviewed and compared with data from another nine patients who developed herpes zoster while taking the drug for rheumatoid arthritis, all from the same university-based arthritis clinic. Literature pertinent to infection in rheumatoid arthritis patients treated with methotrexate is reviewed. Herpes zoster occurred in 14.5 cases per 1,000 patient-years in our methotrexate-treated rheumatoid arthritis patients, as compared with the general population incidence of 1.3 to 4.8 cases per 1,000 patient-years. The infection was unrelated to duration of methotrexate usage, prednisone treatment, or the co-existence of diabetes mellitus, but appeared to occur in patients with high titers of rheumatoid factor and an overall longer duration of rheumatoid arthritis. There were no cases of systemic dissemination or recurrence of herpes zoster despite 27.4 years cumulative follow-up on continued methotrexate therapy. Herpes zoster may occur more frequently in patients with rheumatoid arthritis treated with low-dose methotrexate than in the general population. Herpes zoster in rheumatoid arthritis patients treated with methotrexate appears to be self-limited, benign, and statistically related to methotrexate use in the presence of longer-term rheumatoid disease.

Herpes zoster in patients with rheumatoid arthritis treated with weekly, low-dose methotrexate

purpose: Herpes zoster occurred in nine patients with methotrexate-treated rheumatoid arthritis. We compared these patients to a large group of methotrexate-treated rheumatoid arthritis patients in order to uncover potential factors explaining the occurrence of herpes zoster. patients and methods: Data from 187 patients taking methotrexate were reviewed and compared with data from another nine patients who developed herpes zoster while taking the drug for rheumatoid arthritis, all from the same university-based arthritis clinic. Literature pertinent to infection in rheumatoid arthritis patients treated with methotrexate is reviewed. results: Herpes zoster occurred in 14.5 cases per 1,000 patient-years in our methotrexatetreated rheumatoid arthritis patients, as compared with the general population incidence of 1.3 to 4.8 cases per 1,000 patient-years. The infection was unrelated to duration of methotrexate usage, prednisone treatment, or the co-existence of diabetes mellitus, but appeared to occur in patients with high titers of rheumatoid factor and an overall longer duration of rheumatoid arthritis. There were no cases of systemic dissemination or recurrence of herpes zoster despite 27.4 years cumulative follow-up on continued methotrexate therapy. conclusions: Herpes zoster may occur more frequently in patients with rheumatoid arthritis treated with low-dose methotrexate than in the general population. Herpes zoster in rheumatoid arthritis patients treated with methotrexate appears to be self-limited, benign, and statistically related to methotrexate use in the presence of longer-term rheumatoid disease.

Low-dose methotrexate treatment of rheumatoid arthritis; Long-term observation of efficacy and safety

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.