Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH

N Engl J Med. 1983 Jan 27;308(4):173-80. doi: 10.1056/NEJM198301273080401.


Fifty-eight patients with severe, progressive multiple sclerosis were prospectively randomized to one of three treatments: 20 received intravenous ACTH, 20 received high-dose intravenous cyclophosphamide plus ACTH, and 18 were placed on a regimen consisting of plasma exchange, low-dose oral cyclophosphamide, and ACTH. The three groups were similar in age, sex, duration and type of disease, and degree of disability. Before treatment and six months and one year after treatment, a disability-status score, ambulation index, and functional-status score were determined, and a quantitative neurologic examination was performed. In the ACTH group, the number of patients stabilized or improved was 8 of 20 at six months and 4 of 20 at one year; in the cyclophosphamide-ACTH group, 18 of 20 at six months and 16 of 20 at one year; and in the plasma exchange group, 11 of 18 at six months and 9 of 18 at one year. High-dose cyclophosphamide plus ACTH was most effective in halting progression of the disease at both 6 and 12 months (at 12 months, cyclophosphamide-ACTH vs. ACTH, P = 0.0004; cyclophosphamide-ACTH vs. plasma exchange, P = 0.087). Thus, progressive multiple sclerosis may be stabilized by short-term, intensive immunosuppression with cyclophosphamide plus ACTH.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adrenocorticotropic Hormone / administration & dosage*
  • Adrenocorticotropic Hormone / adverse effects
  • Adult
  • Clinical Trials as Topic
  • Cyclophosphamide / administration & dosage*
  • Cyclophosphamide / adverse effects
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunosuppression Therapy*
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / therapy*
  • Plasma Exchange*
  • Prospective Studies
  • Random Allocation
  • T-Lymphocytes / immunology
  • Time Factors


  • Cyclophosphamide
  • Adrenocorticotropic Hormone