Worldwide safety experience with nabumetone.

Nabumetone has undergone human clinical premarketing and postmarketing testing for efficacy and safety for about 10 years. In the United States and elsewhere, 7,241 patients were evaluated in clinical trials and comparative information with placebo, aspirin, and other nonsteroidal antiinflammatory drugs (NSAID) was gathered. Postmarketing surveillance information was gathered for 37,712 patients in the United Kingdom and Germany. Withdrawal rates due to adverse effects ranged from 3 to 13%. The cumulative incidence of nabumetone-induced perforations, ulcers, or bleeds varied from 0.02 to 0.95%. In all patients evaluated, only 2 deaths and 15 hospitalizations could be attributed to nabumetone therapy. Bone marrow suppression, liver necrosis, serious central nervous system conditions, or life-threatening dermatologic reactions did not occur. No increase in toxicity was noted with increased dose (up to 2000 mg/day) or age. Nabumetone was determined to be a safe NSAID that causes a low incidence of ulcers.

Long-term treatment of rheumatoid arthritis comparing nabumetone with aspirin.

This report summarizes the results of a 17-investigator multicenter six-month randomized double-blind parallel group study. The safety and efficacy of nabumetone 1,000 mg taken at bedtime was compared with that of aspirin 900 mg four times daily in the treatment of adult patients with active class II or III classical or definite rheumatoid arthritis. Two hundred sixty-four patients were entered into the study. Two hundred fifty-seven (126 nabumetone and 131 aspirin) patients were evaluable for safety. Two hundred thirty-four (113 nabumetone and 121 aspirin) patients were evaluable for efficacy. There was significant improvement in each of six clinical measurements of efficacy in both treatment groups and little difference between groups. The somewhat greater improvement in articular index and duration of morning stiffness in the nabumetone-treated group did not reach statistical significance. There was an equal percentage of patient withdrawal for lack of efficacy in each group. Overall, the rate of patient withdrawal due to adverse experiences was greater (p = 0.01) for aspirin-treated patients. These experiences were usually dispepsia, abdominal pain, and tinnitus. It was concluded that nabumetone was an effective anti-inflammatory drug in the treatment of rheumatoid arthritis with less toxicity than aspirin.

Auranofin therapy in rheumatoid arthritis.

Gold is well established as an agent to suppress progressive rheumatoid arthritis. Until recently, gold could only be given parenterally. An orally absorbable gold compound, auranofin, has been undergoing clinical trials in the last 6 years. Auranofin has some effects on the immunologic system, demonstrated in vitro, that differ from its parenteral counterpart, GST. Auranofin appears to have clinical effectiveness in rheumatoid arthritis that approximates that of parenteral gold. Although gastrointestinal toxicity is more frequent with auranofin, renal toxicity is distinctly less frequent than with parenteral gold. There is preliminary evidence that auranofin may have a disease-altering capability, as measured by serial radiographs, similar to that of parenteral gold.

Auranofin treatment for adult rheumatoid arthritis. Comparison of 2 mg and 6 mg daily dose.

Auranofin, an orally effective gold compound, was administered to 2 groups of rheumatoid arthritis patients at 2 mg and 6 mg daily respectively in a controlled study. Both groups showed significant improvement in most efficacy measurements by 6 months. More improvement measurements were observed in the 6 mg group at 3 months than the 2 mg group. Dropout rate because of diarrhea was similar in the 2 groups. Other adverse reactions severe enough to force withdrawal of the test drug were infrequent.

Toxicity of penicillamine. A serious limitation to therapy in rheumatoid arthritis.

A retrospective study of penicillamine toxicity in 156 patients yielded a high incidence of toxic reaction (62%), necessitating discontinuation of the drug therapy in 36% of the patients. Of the total group, proteinuria occurred in 14%, hematologic toxic reaction in 11%, mucocutaneous toxic reaction in 28%, and gastrointestinal intolerance in 12%.

Neuro-Behcet disease: two cases and neuroradiologic findings.

In two cases of Behcet disease, neurologic disorders antedated the characteristic ocular or mucocutaneous lesions by 6 to 32 weeks. Neuroradiologic investigation demonstrated expanding avascular foci in the basal ganglia, probably representing areas of infarction secondary to vasculitis.

Significance of cytoplasmic microtubules in lupus nephritis.

Twenty-five renal and three skin biopsies from 14 cases of systemic lupus erythematosus with lupus nephritis were examined by electron microscope. Seventy-five renal biopsies from nonlupus cases consisting of 35 adults and 40 children were used for comparative study. Clusters of cytoplasmic microtubules, which have been referred to as virus-like particles, were observed in the endothelial cells of glomerular and peritubular capillaries in renal biopsies of all lupus cases. The clusters of microtubules were larger and more numerous in the initial biopsies with mild glomerular changes and in the second biopsies from two cases during a period of more severe relapse. Clusters of microtubules were fewer and smaller in renal biopsies with more advanced glomerular changes. Skin biopsies showed similar cytoplasmic inclusions in arterioles and capillaries. Cytoplasmic microtubules were also observed in 3 adults and 13 children of 75 patients who had no systemic lupus erythematosus. Although the formation of the cytoplasmic microtubules may be related to a virus infection, this suggestion cannot be confirmed from the morphologic findings of this study. Of additional interest is the evidence that these microtubules are not cytoplasmic changes secondary to corticosteroid therapy. It is concluded that the presence of many large clusters of cytoplasmic microtubules is specific for lupus nephritis, and it may be substantiated by similar findings in the skin.