NEUROLOGY 1989;39:1018
© 1989 American Academy of Neurology
A placebo-controlled, randomized, double-masked, variable dosage, clinical trial of azathioprine with and without methylprednisolone in multiple sclerosis
G. W. Ellison, MD,
L. W. Myers, MD,
M. R. Mickey, PhD,
M. C. Graves, MD,
W. W. Tourtellotte, MD, PhD,
K. Syndulko, PhD,
M. I. Holevoet-Howson, RN,
C. D. Lerner, RN,
M. V. Frane, MA and
P. Pettier-Jennings, BS
Department of Neurology, School of Medicine, University of California, Los Angeles, CA (Drs. Ellison, Graves, Myers, Syndulko, and Tourtellotte; Mss. Holevoet-Howson, Lerner, and Frane)
Department of Biomathematics, School of Medicine, University of California, Los Angeles, CA (Dr. Mickey)
Neurology Service, VAMC Wadsworth, Los Angeles, CA (Drs. Syndulko and Tourtellotte; Ms. Pettier-Jennings).
Ninety-eight patients with multiple sclerosis (MS) in the chronic progression phase entered a 3-year clinical trial to determine if azathioprine (AZ) alone or with adrenal cortical steroids stabilizes the course of MS. In group AM, the patients took AZ throughout and methylprednisolone (MP) for the first 36 weeks. Group AP received AZ and placebo instead of MP. Group PP took placebos for both drugs. We adjusted the AZ to maintain the total white blood cell count within 3,000 to 4,000/mm3; we gave the MP in a fixed dose "pulse" and alternate-day regimen. The "intent-to-treat" groups had no statistically significant differences in the rates of progression among the 3 treatments. Subgroup analysis suggests that patients in the AM group who completed treatment exactly according to protocol did statistically significantly better than the placebo recipients using the sum of Standard Neurological Examination scores, slightly better using the quantitative neuro-performance tests, but no better using Mickey's Illness Severity Scores or Kurtzke's Disability Status Scale. Also, the AZ-treated groups had half the relapse rate of the placebo-treated group. Adverse reactions to AZ accounted for most withdrawals. Hematologic and hepatic abnormalities were significantly associated with AZ, but serious non-MS abnormalities were uncommon and were equally distributed among the 3 groups. Addition of MP to the AZ slightly improved the efficacy of the treatment, but also increased the adverse effects. The benefits of AZ with or without steroids did not outweigh the risks, and therefore we do not recommend this treatment for patients with chronic progressive MS.
Address correspondence and reprint requests to Dr. Ellison, Reed Neurological Research Center UCLA, 710 Westwood Plaza, Los Angeles, CA 90024–1769.
Supported by USPHS grants NS-16776 and NS-08711 and grants from the Gustafson Estate and Joe Gheen Barbecue Fund, Department of Neurology, UCLA.
Presented in part at the thirty-eighth annual meeting of the American Academy of Neurology, New Orleans, LA, April 1986.
Received December 7, 1988. Accepted for publication in final form March 9, 1989.
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