Preliminary Results of a Double-Blind, Randomized, Placebo-Controlled Trial of Cyclosporine in Myasthenia Gravis

We randomly assigned 20 patients with progressively worsening generalized myasthenia gravis of recent onset whose illness was not controlled by anticholinesterase therapy to treatment with either cyclosporine (6 mg per kilogram of body weight per day) or placebo. Patients who had been treated with thymectomy, steroids, or other immunosuppressive agents were excluded. The duration of treatment was 12 months. Disease activity was assessed by quantified strength testing and by measurements of antihuman acetylcholine-receptor antibody. Patients were assessed at 6 months and 12 months, or at the following early end points: drug failure (doubling of creatinine), treatment failure (respiratory or swallowing difficulty), or protocol violation (stopping medication for more than five days). At six months, patients in the cyclosporine group had had significantly more objective improvement in strength; one early end point had been reached (drug failure; no treatment failures). In the placebo group, three early end points had been reached (all treatment failures). The decline in titers of acetylcholine-receptor antibody was larger in the treated group, although the difference was not statistically significant. At the end of the study (after 12 months of treatment or arrival at an earlier end point), improvement in strength and reduction in titers of antireceptor antibody continued to be greater in the cyclosporine group. Nephrotoxicity occurred in three patients receiving cyclosporine but was nonprogressive with a reduction in dosage and reversible with discontinuation of the drug. These results are preliminary and need confirmation, but we conclude that cyclosporine is probably an effective therapy in some patients with myasthenia gravis. (N Engl J Med 1987;316:719–24.) MYASTHENIA gravis is a chronic autoimmune disorder in which there is sustained production of an antibody to the nicotinic acetylcholine receptor at the neuromuscular junction. 1 2 3 Both intense and long-term immunosuppressive therapy have been of value in treating this illness, but cumulative side effects limit the usefulness of existing medications. 4 The natural history of myasthenia gravis is one in which the illness becomes most severe in 83 percent of patients within three years after onset. 5 Thus, patients are at risk for progression during the first and second years after onset of the disease, and if immunosuppressive therapy is initiated, it is . . .