No abstract

Objective. To determine whether a regimen of methotrexate, cyclosporin A, and corticosteroids introduced at onset in poor-prognosis rheumatoid arthritis (RA) can produce a significant improvement in outcome compared with standard monotherapy with sulfasalazine (SSZ).Methods. Eighty-two consecutive patients presenting with new, untreated RA of less than 12 months' duration who fulfilled criteria for poor long-term outcome were randomized to receive either combination therapy (n ‫؍‬ 40) or SSZ alone (n ‫؍‬ 42). The primary outcome measures were remission and American College of Rheumatology (ACR) criteria for 20% improvement at 48 weeks.Results. After 48 weeks, the numbers of patients who met the ACR criteria for 20% improvement were not significantly different between the two groups (combination 58% versus SSZ 45%), and similar numbers of patients had persisting clinical remission (ϳ10% both groups). During the first 3 months, there were significantly greater reductions in parameters of disease activity in the combination group. By 24 weeks, the swollen and tender joint counts, C-reactive protein levels, and erythrocyte sedimentation rates had fallen significantly in both groups, with a greater improvement in the swollen and tender joint count in the combination group. At 48 weeks, the radiographic damage score had increased by a median of 1 (range 0-42.5) in the combination group and 1.25 (range 0-72.5) in the SSZ group (P ‫؍‬ 0.28; although there were significant differences in the scores for the right hand). There were significantly fewer withdrawals due to lack of efficacy in the combination group than in the SSZ group (1 of 40 versus 10 of 42; P ‫؍‬ 0.007). In the combination group, dose reduction was needed in 22.5% because of hypertension and in 22.5% because of elevated creatinine levels. Over 48 weeks, serum creatinine increased in both groups, but particularly in the combination arm.

Twenty-six patients with rheumatoid arthritis which was poorly controlled despite high dose D-penicillamine were studied. Compliance was assessed by standard methods (return tablet count and interview). In addition low-dose phenobarbitone was included in the penicillamine formulation as a pharmacological indicator of compliance. Using these techniques incomplete compliance was apparent in 11 patients (42%). All such patients were identified by the pharmacological marker. Only one admitted poor compliance at interview and only six returned more than a few tablets too many. The reason for the high incidence of poor compliance in this selected group is not apparent but it may represent a significant cause of failure with D-penicillamine therapy. The use of low-dose phenobarbitone may have wider applications in the investigation of patients with other conditions who fail to respond adequately to treatment.

Twenty five patients with Raynaud's phenomenon due to systemic sclerosis were infused with prostacyctin (PGI^). In 88",, of the patients there was objective improvement, monitored by thermography or radiometry.The pathogenesis of Raynaud's phenomenon is obscure. Therapy directed at over-activity of the sympathetic system produces only limited or short-lived improvement.Prostaglandins I2 and E, are potent vasodilators and inhibitors of platelet aggregation atid might be expected to produce improvement in peripheral blood fiow. The results of recent studies (Carlson & Eriksson, 1973;Carlson & Olsson, 1976;Szczeklik et al., 1979) suggest that these drugs may help in the management of peripheral vascular disease and ischaemic ulceration.In a previous controlled study of prostaglandin E, in patients with Raynaud's phenomenon and systemic sclerosis, we showed that the drug had a significantly better effect than placebo (Martin et al., I98ia,b).The efficacy of intravenous infusions of prostacyclin (PGI3), a potent vasodilator and more potent inhibitor of platelet aggregation, has now been assessed. PATIENTS AND METHODSThe investigation was performed during the winter months, 1979-1980. Twenty-five patients (twenty-four female, one male) with symptomatic Raynaud's phenomenon and systemic sclerosis were treated with intravenous infusions of prostacyclin.The mean age of the patients was 51 years (range 24-73 years). The mean duration of the Raynaud's phenomenon was I2 years (range 9 months-30 years) and that of other clinical evidence of systemic sclerosis 6 years (range 4 months-i6 years). ooo7-0963/82/oioo-oo8i$02.oo ((J) 1982 British Association of Dermatologists 81