Methotrexate therapy in rheumatoid arthritis: 15 years experience.

An increasing amount of clinical data indicates that low-dose methotrexate therapy for rheumatoid arthritis is both effective and free of serious side effects. Since 1967 we treated 78 patients with definite or classic rheumatoid arthritis who showed inadequate response to conventional therapy. Up to 15 mg of methotrexate was given weekly by the intramuscular route. Morning stiffness, severity of pain at rest and with activity, extent of active synovitis, functional capacity, change in steroid dosage, complete blood count, erythrocyte sedimentation rate, and gamma glutamyl transpeptidase were monitored. Overall assessment indicated that 45 of the 78 (58 percent) patients showed marked improvement or complete remission, usually within four weeks. When maximum improvement was obtained, most patients were switched to oral therapy with a variable degree of success, and dosage was decreased as tolerated. No serious toxicity was noted. In 34 patients a total of 67 liver biopsy specimens were obtained, some after as long as 15 years of therapy. Minor changes observed are the same as in patients with rheumatoid arthritis not treated with methotrexate. Because the risks did not appear justified, routine annual biopsies were discontinued. In contrast to other cytotoxic drugs, no carcinogenesis has been demonstrated with methotrexate. It appears that methotrexate is approximately as effective as intramuscular gold and D-penicillamine but that it has a quicker onset of response and less serious toxicity.

Four-way, multicenter, crossover trial of ibuprofen, fenoprofen calcium, naproxen, and tolmetin sodium in osteoarthritis: comparative clinical profiles.

One hundred forty-one subjects with osteoarthritis completed this double-blind, multicenter, crossover trial comparing four nonsteroidal anti-inflammatory (NSAI) agents after single-blind aspirin stabilization. Preferences of both patients and physicians showed the following rank order from most to least preferable: tolmetin sodium, naproxen, ibuprofen, fenoprofen calcium. By all but three of more than 20 measures of efficacy, tolmetin sodium and naproxen were the more effective pair and fenoprofen calcium and ibuprofen the less effective pair of the four. Eight of nine measures of tolerability suggested the following rank order from best to worst tolerated: ibuprofen, naproxen, tolmetin sodium, fenoprofen calcium, aspirin. Few differences among the newer NSAI agents compared in this study achieved statistical significance. Nevertheless, the tolerability-efficacy relationships that emerge from studies of this type can help to define rational approaches to the use of these drugs in rheumatic diseases.

Fenbufen, a new non-steroidal anti-inflammatory agent in rheumatoid arthritis, its efficacy and toxicity.

Fenbufen, a new butanoic acid derivative with anti-inflammatory properties, was evaluated in an open-label study. It was found that fenbufen was an effective anti-inflammatory agent with tolerable and acceptable potential side-effects. Its advantages appeared to be its long clinical half-life and relatively mild toxicity and/or allergic response.

Naproxen in osteoarthrosis. Double-blind crossover trial.

In this double-blind crossover trial, naproxen (750 mg/day) was compared to placebo for the treatment of osteoarthrosis of the hip and knee. Patients were randomly assigned to treatment with either naproxen or placebo for 4 weeks and then to treatment with the alternate agent for a second 4-week period. 8 out of 9 objective and subjective measurements of drug efficacy clearly differentiated naproxen from placebo at highly significant levels (P = 0.0001 to 0.0004). Patient daily check lists of osteoarthrotic symptoms also showed a statistically significant difference between naproxen and placebo therapy. Both physicians and patients, when asked to give a 'final drug preference', showed a significant preference for naproxen over placebo. In general, the incidence of side effects was low and approximately the same for both naproxen and placebo. Laboratory assessments showed little difference between groups. The trial showed naproxen to be an effective and well tolerated drug for the treatment of osteoarthrosis of the hip and knee.