Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: Final report of the Northeast Cooperative Multiple Sclerosis Treatment Group

H. L. Weiner, G. A. Mackin, E. J. Orav, D. A. Hafler, D. M. Dawson, Y. LaPierre, R. Herndon, J. R. Lehrich, S. L. Hauser, A. Turel, M. Fisher, G. Birnbaum, Justin Charles McArthur, R. Butler, M. Moore, B. Sigsbee, A. Safran

Research output: Contribution to journalArticle

Abstract

Previous studies reported that a 2- to 3-week course of IV cyclophosphamide plus adrenocorticotropic hormone (ACTH) induction can temporarily halt progressive MS for a period of 12 months in the majority of patients treated, after which reprogression occurs. The Northeast Cooperative Multiple Sclerosis Treatment Group was formed to determine whether outpatient pulse cyclophosphamide therapy could affect reprogression and whether there were differences between a modified induction regimen and the previously published regimen. Two hundred fifty-six progressive MS patients were randomized into four groups to receive IV cyclophosphamide/ACTH via the previously published versus a modified induction regimen, with or without outpatient IV cyclophosphamide boosters (700 mg/m2 every other month for 2 years). There were blinded evaluations performed every 6 months. Results demonstrate that (1) there were no differences between the modified and the published induction regimens either in terms of initial stabilization or subsequent progression; (2) without boosters, the majority of patients continued to progress; and (3) in patients receiving boosters, there was a statistically significant benefit at 24 months and 30 months (p = 0.04). Time to treatment failure after 1 year was also significantly prolonged in the booster versus the nonbooster group (p = 0.03). Age was the most important variable that correlated with response to therapy in that amelioration of disease progression occurred primar-ily in patients 40 years of age or younger. Boosters had a significant benefit on time to treatment failure in patients ages 18 to 40, p = 0.003, but not in patients ages 41 to 55, p = 0.97. In addition, patients with primary progressive MS had a poorer prognosis at 12 months than patients with secondarily progressive MS (p = 0.04). Our findings (1) support a role for immunosuppression in the treatment of MS, (2) begin to identify variables that may explain differences between studies of immunosuppression with cyclophosphamide in progressive MS, and (3) suggest that intermittent pulse therapy is an important method for the treatment of progressive MS and perhaps for earlier stages of MS as well.

Original languageEnglish (US)
Pages (from-to)910-918
Number of pages9
JournalNeurology
Volume43
Issue number5
StatePublished - May 1993

Fingerprint

Cyclophosphamide
Multiple Sclerosis
Therapeutics
Treatment Failure
Adrenocorticotropic Hormone
Immunosuppression
Outpatients
Northeast
Pulse
Therapy
Group Treatment
Disease Progression
Induction

ASJC Scopus subject areas

  • Neuroscience(all)
  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

Cite this

Weiner, H. L., Mackin, G. A., Orav, E. J., Hafler, D. A., Dawson, D. M., LaPierre, Y., ... Safran, A. (1993). Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: Final report of the Northeast Cooperative Multiple Sclerosis Treatment Group. Neurology, 43(5), 910-918.

Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis : Final report of the Northeast Cooperative Multiple Sclerosis Treatment Group. / Weiner, H. L.; Mackin, G. A.; Orav, E. J.; Hafler, D. A.; Dawson, D. M.; LaPierre, Y.; Herndon, R.; Lehrich, J. R.; Hauser, S. L.; Turel, A.; Fisher, M.; Birnbaum, G.; McArthur, Justin Charles; Butler, R.; Moore, M.; Sigsbee, B.; Safran, A.

In: Neurology, Vol. 43, No. 5, 05.1993, p. 910-918.

Research output: Contribution to journalArticle

Weiner, HL, Mackin, GA, Orav, EJ, Hafler, DA, Dawson, DM, LaPierre, Y, Herndon, R, Lehrich, JR, Hauser, SL, Turel, A, Fisher, M, Birnbaum, G, McArthur, JC, Butler, R, Moore, M, Sigsbee, B & Safran, A 1993, 'Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: Final report of the Northeast Cooperative Multiple Sclerosis Treatment Group', Neurology, vol. 43, no. 5, pp. 910-918.
Weiner, H. L. ; Mackin, G. A. ; Orav, E. J. ; Hafler, D. A. ; Dawson, D. M. ; LaPierre, Y. ; Herndon, R. ; Lehrich, J. R. ; Hauser, S. L. ; Turel, A. ; Fisher, M. ; Birnbaum, G. ; McArthur, Justin Charles ; Butler, R. ; Moore, M. ; Sigsbee, B. ; Safran, A. / Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis : Final report of the Northeast Cooperative Multiple Sclerosis Treatment Group. In: Neurology. 1993 ; Vol. 43, No. 5. pp. 910-918.
@article{a37094e88c4e4320b37d3666ecfcefba,
title = "Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: Final report of the Northeast Cooperative Multiple Sclerosis Treatment Group",
abstract = "Previous studies reported that a 2- to 3-week course of IV cyclophosphamide plus adrenocorticotropic hormone (ACTH) induction can temporarily halt progressive MS for a period of 12 months in the majority of patients treated, after which reprogression occurs. The Northeast Cooperative Multiple Sclerosis Treatment Group was formed to determine whether outpatient pulse cyclophosphamide therapy could affect reprogression and whether there were differences between a modified induction regimen and the previously published regimen. Two hundred fifty-six progressive MS patients were randomized into four groups to receive IV cyclophosphamide/ACTH via the previously published versus a modified induction regimen, with or without outpatient IV cyclophosphamide boosters (700 mg/m2 every other month for 2 years). There were blinded evaluations performed every 6 months. Results demonstrate that (1) there were no differences between the modified and the published induction regimens either in terms of initial stabilization or subsequent progression; (2) without boosters, the majority of patients continued to progress; and (3) in patients receiving boosters, there was a statistically significant benefit at 24 months and 30 months (p = 0.04). Time to treatment failure after 1 year was also significantly prolonged in the booster versus the nonbooster group (p = 0.03). Age was the most important variable that correlated with response to therapy in that amelioration of disease progression occurred primar-ily in patients 40 years of age or younger. Boosters had a significant benefit on time to treatment failure in patients ages 18 to 40, p = 0.003, but not in patients ages 41 to 55, p = 0.97. In addition, patients with primary progressive MS had a poorer prognosis at 12 months than patients with secondarily progressive MS (p = 0.04). Our findings (1) support a role for immunosuppression in the treatment of MS, (2) begin to identify variables that may explain differences between studies of immunosuppression with cyclophosphamide in progressive MS, and (3) suggest that intermittent pulse therapy is an important method for the treatment of progressive MS and perhaps for earlier stages of MS as well.",
author = "Weiner, {H. L.} and Mackin, {G. A.} and Orav, {E. J.} and Hafler, {D. A.} and Dawson, {D. M.} and Y. LaPierre and R. Herndon and Lehrich, {J. R.} and Hauser, {S. L.} and A. Turel and M. Fisher and G. Birnbaum and McArthur, {Justin Charles} and R. Butler and M. Moore and B. Sigsbee and A. Safran",
year = "1993",
month = "5",
language = "English (US)",
volume = "43",
pages = "910--918",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis

T2 - Final report of the Northeast Cooperative Multiple Sclerosis Treatment Group

AU - Weiner, H. L.

AU - Mackin, G. A.

AU - Orav, E. J.

AU - Hafler, D. A.

AU - Dawson, D. M.

AU - LaPierre, Y.

AU - Herndon, R.

AU - Lehrich, J. R.

AU - Hauser, S. L.

AU - Turel, A.

AU - Fisher, M.

AU - Birnbaum, G.

AU - McArthur, Justin Charles

AU - Butler, R.

AU - Moore, M.

AU - Sigsbee, B.

AU - Safran, A.

PY - 1993/5

Y1 - 1993/5

N2 - Previous studies reported that a 2- to 3-week course of IV cyclophosphamide plus adrenocorticotropic hormone (ACTH) induction can temporarily halt progressive MS for a period of 12 months in the majority of patients treated, after which reprogression occurs. The Northeast Cooperative Multiple Sclerosis Treatment Group was formed to determine whether outpatient pulse cyclophosphamide therapy could affect reprogression and whether there were differences between a modified induction regimen and the previously published regimen. Two hundred fifty-six progressive MS patients were randomized into four groups to receive IV cyclophosphamide/ACTH via the previously published versus a modified induction regimen, with or without outpatient IV cyclophosphamide boosters (700 mg/m2 every other month for 2 years). There were blinded evaluations performed every 6 months. Results demonstrate that (1) there were no differences between the modified and the published induction regimens either in terms of initial stabilization or subsequent progression; (2) without boosters, the majority of patients continued to progress; and (3) in patients receiving boosters, there was a statistically significant benefit at 24 months and 30 months (p = 0.04). Time to treatment failure after 1 year was also significantly prolonged in the booster versus the nonbooster group (p = 0.03). Age was the most important variable that correlated with response to therapy in that amelioration of disease progression occurred primar-ily in patients 40 years of age or younger. Boosters had a significant benefit on time to treatment failure in patients ages 18 to 40, p = 0.003, but not in patients ages 41 to 55, p = 0.97. In addition, patients with primary progressive MS had a poorer prognosis at 12 months than patients with secondarily progressive MS (p = 0.04). Our findings (1) support a role for immunosuppression in the treatment of MS, (2) begin to identify variables that may explain differences between studies of immunosuppression with cyclophosphamide in progressive MS, and (3) suggest that intermittent pulse therapy is an important method for the treatment of progressive MS and perhaps for earlier stages of MS as well.

AB - Previous studies reported that a 2- to 3-week course of IV cyclophosphamide plus adrenocorticotropic hormone (ACTH) induction can temporarily halt progressive MS for a period of 12 months in the majority of patients treated, after which reprogression occurs. The Northeast Cooperative Multiple Sclerosis Treatment Group was formed to determine whether outpatient pulse cyclophosphamide therapy could affect reprogression and whether there were differences between a modified induction regimen and the previously published regimen. Two hundred fifty-six progressive MS patients were randomized into four groups to receive IV cyclophosphamide/ACTH via the previously published versus a modified induction regimen, with or without outpatient IV cyclophosphamide boosters (700 mg/m2 every other month for 2 years). There were blinded evaluations performed every 6 months. Results demonstrate that (1) there were no differences between the modified and the published induction regimens either in terms of initial stabilization or subsequent progression; (2) without boosters, the majority of patients continued to progress; and (3) in patients receiving boosters, there was a statistically significant benefit at 24 months and 30 months (p = 0.04). Time to treatment failure after 1 year was also significantly prolonged in the booster versus the nonbooster group (p = 0.03). Age was the most important variable that correlated with response to therapy in that amelioration of disease progression occurred primar-ily in patients 40 years of age or younger. Boosters had a significant benefit on time to treatment failure in patients ages 18 to 40, p = 0.003, but not in patients ages 41 to 55, p = 0.97. In addition, patients with primary progressive MS had a poorer prognosis at 12 months than patients with secondarily progressive MS (p = 0.04). Our findings (1) support a role for immunosuppression in the treatment of MS, (2) begin to identify variables that may explain differences between studies of immunosuppression with cyclophosphamide in progressive MS, and (3) suggest that intermittent pulse therapy is an important method for the treatment of progressive MS and perhaps for earlier stages of MS as well.

UR - http://www.scopus.com/inward/record.url?scp=0027196941&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027196941&partnerID=8YFLogxK

M3 - Article

C2 - 8388090

AN - SCOPUS:0027196941

VL - 43

SP - 910

EP - 918

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 5

ER -