Cyclosporin A Treatment of Refractory Rheumatoid Arthritis

Abstract

Ten patients with rheumatoid arthritis were entered into a 24-week pilot study of oral cyclosporin A at a starting dosage of 6 mg/kg/day, followed by a 12-week washout period. Significant improvement in clinical parameters was observed at 12 weeks and 24 weeks (P < 0.02 versus baseline for joint pain and joint swelling indexes and patient and physician assessments; P < 0.04 versus baseline in the numbers of painful/ tender joints and swollen joints). Adverse reactions were varied: renal impairment occurred in all patients and hypertension occurred in 7. All patients demonstrated an increase in defined disease activity at cessation of treatment and through the washout period. Cyclosporin A is clinically effective in the treatment of patients with refractory rheumatoid arthritis, but its value as an intervention therapy is limited by its toxicity.Patients with rheumatoid arthritis (RA) are generally treated with antiinflammatory drugs and with possible disease-modifying agents such as gold salts, hydroxychloroquine, or penicillamine (1-3). When this approach has been unsuccessful, either because of

Human synovial mast cells. II. Heterogeneity of the pharmacologic effects of antiinflammatory and immunosuppressive drugs

“…Low doses of CSA are effective in the treatment of some patients with rheumatoid arthritis (30)(31)(32) and other inflammatory arthritides (33). Our results suggest that the beneficial effects of CSA in these patients are due, to some extent, to the inhibitory effect of pharmacologic concentrations of CSA on the release of proinflammatory mediators from HSyMC.…”

“…We examined 2 classes of immunosuppressive drugs: CSA and CSH as well as FK-506 and rapamycin, which bind to a family of cytoplasmic receptors, immunophilins, and MTX. Low doses of MTX (45) or of CSA (30)(31)(32) can be effective treatments in some patients with arthritis. There is also evidence that FK-506 and rapamycin exert antiinflammatory effects in some models of arthritis (42,43).…”

“…Characterization of the molecular site of action of CSA is critical for the rational and optimal therapeutic use of this agent in various forms of arthritis (30)(31)(32)(33) and for the search for new CSA-like drugs. Two mechanisms whereby cyclosporins exert their antiinflammatory activity have been proposed.…”

“…There is increasing evidence that low-dose CSA is effective in the treatment of patients with rheumatoid arthritis (30)(31)(32) and other inflammatory arthritides (33). In this series of experiments, we compared the effects of CSA and CSH, which bind with different affinities to cyclophilin (34), on the release of inflammatory mediators from HSyMC in order to evaluate their roles in this process.…”

Corticosteroid Refractory Radiation Pneumonitis that Remarkably Responded to Cyclosporin A.

“…CsA is a well-established immunosuppressant thatactson CD4+T cells byblockingtranscription of the interleukin-2 gene.Thisagenthasbeenappliedto patientswithautoimmune connective tissuedisease in addition to organtransplantation (17)(18)(19)(20). Theefficacyof this agentforseveraldiseasescombinedwithinterstitial pneumonitis is recognized.…”