The New England Journal of Medicine -- September 28, 2000 -- Vol. 343, No. 13
Lawrence D. Jacobs, Roy W. Beck, Jack H. Simon, R. Phillip Kinkel, Carol M. Brownscheidle, Thomas J. Murray, Nancy A. Simonian, Peter J. Slasor, Alfred W. Sandrock, the CHAMPS Study Group
Background. Treatment with interferon beta has been shown to help patients with established multiple sclerosis, but it is not known whether initiating treatment at the time of a first clinical demyelinating event is of value.
We conducted a randomized, double-blind trial of 383 patients who had a first acute clinical demyelinating event (optic neuritis, incomplete transverse myelitis, or a brain-stem or cerebellar syndrome) and evidence of prior subclinical demyelination on magnetic resonance imaging (MRI) of the brain. After initial treatment with corticosteroids, 193 patients were randomly assigned to receive weekly intramuscular injections of 30 µg of interferon beta-1a and 190 were assigned to receive weekly injections of placebo. The study end points were the development of clinically definite multiple sclerosis and changes in findings on MRI of the brain. The trial was stopped after a preplanned interim efficacy analysis.
During three years of follow-up, the cumulative probability of the development of clinically definite multiple sclerosis was significantly lower in the interferon beta-1a group than in the placebo group (rate ratio, 0.56; 95 percent confidence interval, 0.38 to 0.81; P=0.002). As compared with the patients in the placebo group, patients in the interferon beta-1a group had a relative reduction in the volume of brain lesions (P<0.001), fewer new or enlarging lesions (P<0.001), and fewer gadolinium-enhancing lesions (P<0.001) at 18 months.
Initiating treatment with interferon beta-1a at the time of a first demyelinating event is beneficial for patients with brain lesions on MRI that indicate a high risk of clinically definite multiple sclerosis. (N Engl J Med 2000;343:898-904.)
From the Department of Neurology, State University of New York School of Medicine at Buffalo and Buffalo General Hospital, Buffalo (L.D.J., C.M.B.); the Jaeb Center for Health Research, Tampa, Fla. (R.W.B.); the Department of Radiology-MRI, University of Colorado Health Sciences Center, Denver (J.H.S.); the Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Foundation, Cleveland (R.P.K.); the Multiple Sclerosis Research Unit, Centre for Clinical Research, Victoria General Hospital, Queen Elizabeth II Health Sciences Centre, Halifax, N.S., Canada (T.J.M.). and Biogen, Cambridge, Mass. (N.A.S., P.J.S., A.W.S.). Address reprint requests to Dr. Jacobs at the Department of Neurology, Buffalo General Hospital, 100 High St., Buffalo, NY 14203, or at firstname.lastname@example.org.
Other participants in the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) are listed in the Appendix.
Other participants in the study were as follows: Clinical Centers --
University of Toronto: P. O'Connor, P. Fleming, T. Gray; Buffalo General
Hospital: C. Miller, R. Bakshi, F. Munschauer; Cleveland Clinic Foundation:
D. Bolibrush, J. Cohen; Ottawa General Hospital: M. Freedman, U. Webb,
H Rabinowicz; Foothills Hospital: L. Metz, A. Davis, R. Ranawaya;
Vancouver Hospital and Health Sciences Center: S. Hashimoto, W. Morrison,
J. Oger; University of Maryland Hospital: H. Panitch, K. Costello, C. Bever;
Multiple Sclerosis Center at Shepherd: W. Stuart, D. Court, D. Stuart;
Georgetown University Hospital: C. Tornatore, D. Bartlett, J. Richert;
Hopital Notre Dame: P. Duquette, R. Dubois, G. Bernier; Allegheny Neurological
Associates: T. Scott, L. Pappert, J. Brillman; Medical College of Virginia,
Richmond Eye and Ear Hospital: W. Fenton, III, T. Anderson, J. Astruc;
Salt Lake City Veterans Affairs Medical Center: J. Rose, J. Kline, J. Burns;
Victoria General Hospital: P. Weldon, F. Bhan; University of Iowa College
of Medicine: M. Wall, L. Vining, T. Grabowski; New York Hospital-Cornell
Medical Center: B. Apatoff, K. Arapello, J. Friedman; University of Pennsylvania
Medical Center: S. Galetta, D. Pfohl, G. Liu; London Health Sciences Centre
University Hospital: G. Rice, T. Bental, P. Mandalfino; Michigan State
University: E. Eggenberger, D. Snider, D. Kaufman; Yale School of Medicine:
J. Guarnaccia, M. Shepard, J. Goldstein; Beta Research, Inc.: M. Reiss,
E. Carter, G. Glista; Marshfield Clinic: L. Rolak, L. Scheller, D. Jacobson;
University of Rochester: A. Goodman, M. Petrie, D. Mattson; Rush-Presbyterian-St.
Luke's Medical Center: K. Karlin, A. Wallin, D. Stefoski; University of
Texas Health Science Center: S. Brod, E. Cerretta, J. Wolinsky; Montreal
Neurological Institute: D. Arnold, R. Arnoutelis, L. Durcan; Beth Israel
Medical Center: M. Kupersmith, L. Cappolino, J. Herbert; Southern California
Kaiser Permanente Medical Center: J. Rosenberg, D. McHugh, A. Blumenfeld;
Swedish Medical Center: C. Smith, D. Kuder, S. Hamilton; Neurological Associates,
Inc.: S. Thurston, J. McGee, J. O'Bannon; Carolinas Medical Center: M.
Kaufman, M. Butler, S. Putnam; Ohio State University: K. Rammohan, A. Siffort,
J. Lynn; St. Louis University Health Sciences Center: J. Selhourst, E.
Holzemer, G. Hayat; Wayne State University School of Medicine: A. Tselis,
C. Caon, R. Lisak: Massachusetts General Hospital: S. Wray, P. Sexton,
J. Lehrich; University of Medicine and Dentistry of New Jersey Medical
School: S. Cook, A. Jotkowitz, S. Bansil; Emory Clinic: N. Newman, J. Brown,
P. Pennell; Mayo Clinic Arizona: J. Carter, J. Buckner, R. Caselli; Neurology
Group: L. Kerson, M. Camasso, G. Donneief; East Bay Neurology, Inc.: J.
Cooper, D. Salkovsky, H. Shale; University of Illinois Eye and Ear Infirmary:
J. Goodwin, T. Johnson, A. Gulati; New England Medical Center: T. Hedges,
C. Yardley, T. Tran; University of Missouri: S. Horowitz, A. Bonnett, R.
Burger; Kaiser Permanente Medical Center: J. Javerbaum, C. Griffin, R.J.
Whaley; Bowman Gray School of Medicine of Wake Forest University: D. Jeffery,
S.E. Jackson, E. Bastings; Dartmouth-Hitchcock Medical Center: L. Kasper,
K. Ryan, J. Bernat; Oregon Health Sciences University: M. Mass, S. Cooper
Hanel, D. Bourdette; University of Florida: J. Guy, M. Wilson, M. Greer;
Mayo Clinic: C. Lucchinetti, M. Botten, J. Noseworthy; Medical University
of South Carolina: A. Walker, B. Muntz, W. Tyor; MRI Reading Center, University
of Colorado Health Sciences Center -- M. Meyer, R. Leek, C. Gustafson,
D. Singel, B. Quandt, D.E. Miller, B. Coombs, A. Cajade-Law, M. Lajaunie;
End-Point Committee -- A. Miller (chair), J. Richert, J. Cohen, T. Vollmer,
J. Oger; Advisory Committee -- L. Jacobs (cochair), R. Beck (cochair),
R.P. Kinkel, C. Brownscheidle, T.J. Murray, J. Simon; Data and Safety Monitoring
Committee -- J. Antel (chair), L. Myers, G. Birnbaum, S. Reingold, R. Burde,
W. Sibley, J. Ware; Biogen -- N. Blanchard, K. Lloyd, H. Park, F. Votruba,