Methotrexate in rheumatoid arthritis. Impact on quality of life assessed by traditional standard-item and individualized patient preference health status questionnaires.

In a double-blind, randomized trial of methotrexate vs placebo in rheumatoid arthritis, the effect of treatment on physical, social, and emotional function was measured in two different ways: the same, standard measurements in all patients, and individualized measurements selected by the patients at the start of the trial as representing the functions they most wanted to have improved by treatment. On the standard measurements, methotrexate-treated patients fared better than placebo-treated patients in their physical, social, and emotional function by 11%, 5%, and 6%, respectively, results that, although statistically significant, were small. However, methotrexate-treated patients were 29% better in the individualized measures, a result that was both highly statistically significant and greater than the differences in the standard measurements or in joint counts, grip strength, proximal interphalangeal joint circumference, morning stiffness, or walking time. Because the individualized measurements were as efficient as the best direct joint examination measures, yet reflected functional outcomes of greatest importance to individual patients, they constitute useful measures for such trials.

A clinical evaluation of piroxicam gel: an open comparative trial with diclofenac gel in the treatment of acute musculoskeletal disorders.

An open, parallel trial was conducted to compare the efficacy and toleration of piroxicam 0.5% gel and diclofenac 1.16% topical gel preparations in the treatment of 173 patients with well-defined, acute sprains and tendinitis of the ankle, shoulder, or elbow. Therapy was begun within three to five days of the injury and continued for up to 14 days. Piroxicam gel was applied to the injured area four times daily by 84 patients and diclofenac gel was similarly applied by 89 patients. Pain, tenderness, and restriction of joint movement were markedly improved with both drugs after three days of treatment. Further improvement was noted after 14 days of treatment and patients generally resumed normal activities in nine days. There was no difference in the response to treatment or in the global impressions of efficacy between piroxicam and diclofenac. Toleration was regarded as good or excellent by 98% of patients receiving piroxicam and 94% of patients receiving diclofenac. There were few adverse effects reported by either group. The type and incidence of these effects were similar for both drugs, with the majority consisting of mild or moderate local skin reactions at the site of application. The results of this study show that piroxicam 0.5% gel and diclofenac 1.16% gel are equally effective and well tolerated in the treatment of selected acute sprains and tendinitis.

Piroxicam: new dosage forms.

Patient acceptance of medications often depends upon individual and cultural preferences for particular dosage forms. A variety of dosage forms also provides the patient and the physician with greater convenience and flexibility. Thus, multiple formulations increase the clinical utility of a drug. In addition to the capsule, dosage forms of piroxicam now available or in an advanced stage of clinical development include a suppository, dispersible tablet, topical gel, and parenteral formulation. (Ed.: The parenteral and topical formulations were launched after the symposium was held, and are now available). The piroxicam suppository offers an alternative to the oral route of administration. Pharmacokinetic studies demonstrate that the 20-mg suppository is bioequivalent to the 20-mg capsule, and clinical studies have shown that it is equal to the capsule in efficacy and toleration. Piroxicam is the only non-steroidal anti-inflammatory drug (NSAID) that is available as a dispersible tablet. This dosage form is also well tolerated by patients and equally effective as the capsule. Intramuscular administration of piroxicam is in development. All these dosage forms offer the convenience of once-a day administration. Piroxicam topical gel (0.5%) has been demonstrated to have anti-inflammatory activity in several animal models. In double-blind clinical trials involving patients with osteoarthritis of the knee, the topical gel was found to be significantly more effective than placebo and well tolerated.

The clinical pharmacology of piroxicam.

Piroxicam, a potent inhibitor of prostaglandins, is effective and well-tolerated in the treatment of primary dysmenorrhea. A single 40 mg dose has been shown to rapidly reduce the uterine hypercontractility of primary dysmenorrhea. In clinical trials vs placebo, piroxicam in a dose of 40 mg once daily for two days followed by 20 mg once daily thereafter demonstrated superior efficacy. In more than 1,400 piroxicam-treated menstrual cycles and more than 200 placebo-controlled cycles, a similar incidence of side effects-7% and 8.4% respectively-was observed.

Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial.

One hundred eighty-nine patients with rheumatoid arthritis were entered into a prospective, controlled, double-blind multicenter trial comparing placebo and methotrexate (MTX). One hundred ten patients completed 18 weeks of therapy. No remissions were seen, but patients able to tolerate low-dose pulse MTX therapy were significantly improved, compared with patients receiving placebo therapy, for all clinical variables measured, including joint pain/tenderness and swelling counts, rheumatoid nodules, and patient and physician assessment of disease activity. MTX treatment demonstrated statistically significant improvement over placebo in patients with anemia, elevated erythrocyte sedimentation rate, and rheumatoid factor. However, nearly one-third of the patients receiving MTX were withdrawn for adverse drug reactions, of which elevated levels of liver enzymes was the most common. Pancytopenia occurred in 2 patients taking MTX. All adverse drug effects resolved without sequelae. MTX appears to be effective in the treatment of active rheumatoid arthritis but requires close monitoring for toxicity.

Azathioprine versus D-penicillamine in rheumatoid arthritis patients who have been treated unsuccessfully with gold.

Two hundred six patients were entered into a prospective controlled, double-blind, multicenter trial comparing azathioprine (AZA) 1.25-1.5 mg/kg/day with D-penicillamine (DP) 10-12 mg/kg/day. One hundred thirty-four patients completed 24 weeks of therapy. Improvement in nearly all efficacy variables was seen in both groups. Patients taking DP demonstrated a greater rise in hemoglobin concentration and greater fall in erythrocyte sedimentation rate than patients receiving AZA; these were the only efficacy variables with a significant difference between the treatment groups. Fewer withdrawals for adverse reactions occurred among the patients receiving AZA, but the difference was not significant. Patients receiving AZA were withdrawn from the drug mainly for abnormal liver function test results, nausea and gastrointestinal upset, and leukopenia. The main reasons for withdrawal of patients receiving DP were nausea, rash and pruritus, thrombocytopenia, dysgeusia, and proteinuria.

Low-dose D-penicillamine therapy in rheumatoid arthritis. A controlled, double-blind clinical trial.

Two hundred twenty-five patients with active severe rheumatoid arthritis were admitted to a multiclinic, controlled, double-blind trial comparing the use of 500 mg D-penicillamine per day, 125 mg D-penicillamine per day, and placebo. One hundred seventy-one patients completed at least 30 weeks of therapy. The 500 mg D-penicillamine group demonstrated statistically significant improvement over the placebo group in grip strength, average circumference of swollen proximal interphalangeal joints, and patient assessment. While the trend was for greater improvement with the larger dose of D-penicillamine, there was no statistically significant difference among the 3 groups in duration of morning stiffness, walking time, physician's assessment, number of swollen joints, or scores for tender and swollen joints. The slight increase in efficacy of higher dose D-penicillamine was associated with increased toxicity.

Pulmonary function in scleroderma.

Pulmonary function tests were performed in 45 patients with scleroderma. Thirteen patients (29%) were found to have restrictive disease, 12 patients (27%) were found to have obstructive disease, and 19 patients (42%) had small airway disease (SAD). Smoking did not seem to be a factor underlying either obstructive or small airway disease in these patients. A low diffusing capacity was most common in patients with restrictive disease and rarely the only abnormality in pulmonary function. SAD was usually found in patients who had normal chest radiographs and no pulmonary symptoms and was often the only abnormality. SAD is therefore an early and sensitive indicator of pulmonary involvement in scleroderma.

Colchicine in the treatment of scleroderma.

We treated 10 patients with well established scleroderma with colchicine in the highest tolerated dose for one year. We could determine no clinical or laboratory improvement in any patient. Progression of disease was suggested by the development of new skin ulcers and telangiectasia, by an increase in musculoskeletal complaints, and by a significantly diminished ability to make a fist. In addition, there was deterioration of pulmonary function as demonstrated by a statistically significant fall in FEV1, and diffusing capacity. Colchicine was not of value in the treatment of scleroderma in this group of patients.

Prednisone and azathioprine compared to prednisone plus low-dose azathioprine and cyclophosphamide in the treatment of diffuse lupus nephritis.

A 1-year double-blind crossover study comparing prednisone and azathioprine to prednisone plus low-dose azathioprine and cyclophosphamide was carried out in 14 patients with diffuse lupus nephritis. Low-dose triple therapy had no apparent therapeutic advantage over prednisone plus azathioprine. Cyclophosphamide-induced ovarian failure and hematuria were not avoided by its use in low dose.