One hundred and forty-five patients suffering from diseases requiring long-term treatment with high doses of corticosteroids (30 mg/day or greater of prednisolone) were recruited to the study. Patients had to be steroid naive on entry to the study (not more than 15 days of treatment with a corticosteroid within the previous 24 months). Patients were randomized to receive either 1 microgram/day alfacalcidol or placebo capsules for 12 months. Bone mineral density (BMD) of the lumbar spine was assessed by dual-photon absorptiometry on entry and after 3, 6 and 12 months' treatment. Safety was monitored by the recording of all adverse events reported by patients and the regular screening of blood samples for hematology and serum biochemistry. Of the 145 patients, 74 were randomized to alfacalcidol and 71 to placebo. The treatment groups were well matched at baseline with no significant differences in demographic, clinical or biochemical parameters. The mean equivalent dose of prednisolone at baseline was 46.6 mg/day and 46.3 mg/day for the alfacalcidol and placebo group respectively. From the 145 patients randomized to treatment, 71 (38 who received alfacalcidol and 33 who received placebo) provided BMD data both at baseline and at 3, 6 and 12 months. The percentage change in BMD after 6 months' treatment was -2.11% in the alfacalcidol group and -4.00% in the placebo group (p = 0.39). After 12 months the percentage change in BMD was +0.39% (CI: -4.28 to 4.81) in the alfacalcidol group and -5.67% (CI: -8.13 to -3.21) in the placebo group, this difference (6.06%, CI: 0.88 to 11.24) being statistically significant (p = 0.02). An intention to treat analysis also showed a significant difference between the two treatment groups in alfacalcidol's favor (3.81%, p = 0.01; CI: 0.92 to 6.70). There was no significant difference between the two treatment groups in the corticosteroid dose at any time point during the study. Serum calcium was measured throughout and there were no significant differences between the two treatment groups at any visit. This study suggests that alfacalcidol can prevent corticosteroid-induced bone loss from the lumbar spine. Long-term use of alfacalcidol was not associated with any significant adverse effects in this diverse group of patients.

This double-blind, parallel group study was conducted to evaluate the gastroduodenal safety and antiarthritic efficacy of a fixed combination of diclofenac sodium 50 mg and misoprostol 200 mcg, compared with a combination of diclofenac 50 mg and placebo. Three hundred and thirty-nine patients with rheumatoid arthritis and no significant gastric or duodenal mucosal damage were enrolled and received study medication (diclofenac/misoprostol, 164; diclofenac/placebo, 175) BID or TID for 12 weeks. Posttreatment gastroduodenal endoscopic examinations revealed ulcers in 11% of the diclofenac/placebo group, compared with only 4% of the diclofenac/misoprostol group (p = 0.034). Four-weekly assessments of arthritic condition revealed no clinically or statistically significant treatment differences. It was concluded that diclofenac/misoprostol caused significantly less gastroduodenal damage than diclofenac, but was as effective as diclofenac alone in the treatment of rheumatoid arthritis.

Oral gold (auranofin) has been used in 31 patients, 20 with active rheumatoid arthritis and 11 with active psoriatic arthritis. In rheumatoid arthritis the oral gold treatment was compared to parenteral gold treatment in a patient blind trial for two years. The psoriatic arthritis cases were incorporated in an open trial. Auranofin 6 mg once daily reduced significantly the activity in rheumatoid arthritis and in psoriatic arthritis. The beneficial effect obtained with auranofin at a dose of 6 mg/day during the first year of treatment could not be maintained by 3 mg/day in the second year. Auranofin compared to parenteral gold had a distinct advantage of better systemic tolerability, although parenteral gold was found to be more potent. There was no greater risk for toxic skin reaction to oral gold in psoriatic arthritis than in rheumatoid arthritis. The overall conclusion of this longterm study is that oral gold (auranofin) 6 mg once daily, although slightly less effective than parenteral gold, can be considered to be the first choice of gold treatment for rheumatoid arthritis and psoriatic arthritis, because the compliance, which is a reflection of a combination of tolerance and efficacy, for oral gold therapy was, in our hands, undoubtedly superior to parenteral gold.

The effects of lymphoplasmapheresis on immunologic indices, including T cell subsets, and on clinical parameters of rheumatoid arthritis were evaluated in a controlled double-blind trial. Twenty patients were randomized to receive either 6 lymphoplasmapheresis sessions or a seemingly identical control procedure over a 3-week period. Lymphoplasmapheresis produced significant reduction in serum levels of total lymphocytes, erythrocyte sedimentation rate, C-reactive protein, and IgG. These serologic measures returned to baseline 5 weeks after lymphoplasmapheresis. No change in the imbalance of T cell subsets (increased helper/suppressor ratio) was observed. No changes in the serologic measures, except IgA, were observed in the control group. An improvement in some of the clinical parameters was observed in both the lymphoplasmapheresis and control groups. A rebound above baseline values for several parameters was observed in both the lymphoplasmapheresis and the sham apheresis groups.

We evaluated the effects of a nonsteroidal antiinflammatory drug, naproxen, on phytohemagglutinin (PHA)–induced lymphocyte proliferation. When added in vitro to cultures of peripheral blood mononuclear cells, naproxen enhanced the proliferative response toward PHA of lymphocytes from rheumatoid arthritis (RA) patients but not from healthy volunteers, and it reduced prostaglandin E2 (PGE2) synthesis in the cultures. Oral treatment for 7 days with naproxen also resulted in a significant enhancement of the in vitro PHA‐induced proliferation of lymphocytes from RA patients and from age‐matched control patients with noninflammatory rheumatic diseases, but not from young healthy controls. This enhancement of PHA‐induced lymphocyte proliferation after oral intake of naproxen was not accompanied by diminished in vitro PGE2 production in the cultures. It did occur when PGE2‐producing monocytes were removed and when in vitro PGE2 synthesis was blocked with indomethacin. We conclude that oral treatment with naproxen has an immunomodulatory effect and improves in vitro PHA‐induced proliferation of lymphocytes from rheumatic disease patients. This effect is not due to reduced PGE2 synthesis in the in vitro cultures, but reflects a more fundamental in vivo change in immunoregulation.