The peculiar difficulties of therapeutic trials for multiple sclerosis

Because the immune response appears important in the pathogenesis of MS, anti-inflammatory and immunomodulatory drugs and agents are used as a palliative treatment. Azathioprine alone is minimally efficacious and probably not worth the bother and risk. Cyclophosphamide alone is too toxic. Although cyclosporine A may slow the rate of deterioration in chronic progressive MS, adverse effects may limit its use outside major centers. Gamma interferon provokes exacerbations and should not be used. We do not recommend copolymer-1, alpha or beta interferon, monoclonal antibodies, plasmapheresis, and total lymphoid irradiation except in well-designed experimental protocols. Combination therapy of adrenal cortical steroids (ACS) with other immunosuppressants (cyclophosphamide or cyclosporine) merits further study. We think "pulse" synthetic ACS therapy has advantages over corticotropin and will become the "standard of care" for exacerbations. We also would try it for chronic progression. Even then, with the pulse treatment we still must determine the optimum dose, route, duration, and need for "taper."