Results of the Avonex Combination Trial (ACT) in relapsing-remitting MS.
OBJECTIVE
To assess the safety, tolerability, and efficacy of interferon beta-1a (IFNbeta-1a) combined with methotrexate (MTX), i.v. methylprednisolone (IVMP), or both in patients with relapsing-remitting multiple sclerosis (RRMS) with continued disease activity on IFNbeta-1a monotherapy.


METHODS
Eligibility criteria included RRMS, Expanded Disability Status Scale score 0-5.5, and > or = 1 relapse or gadolinium-enhancing MRI lesion in the prior year on IFNbeta-1a monotherapy. Participants continued weekly IFNbeta-1a 30 microg i.m. and were randomized in a 2 x 2 factorial design to adjunctive weekly placebo or MTX 20 mg p.o., with or without bimonthly IVMP 1,000 mg/day for 3 days. The primary endpoint was new or enlarged T2 lesion number at month 12 vs baseline. The study was industry-supported, collaboratively designed, and governed by an investigator Steering Committee with independent Advisory and Data Safety Monitoring committees. Study operations, MRI analyses, and aggregated data were managed by an academic coordinating center.


RESULTS
The 313 participants had clinical and MRI characteristics typical of RRMS. Combinations of IFNbeta-1a with MTX or IVMP were generally safe and well tolerated. Although trends suggesting modest benefit were seen for some outcomes for IVMP, the results did not demonstrate significant benefit for either adjunctive therapy. The data suggested IVMP reduced anti-IFNbeta neutralizing antibody titers.


CONCLUSIONS
This trial did not demonstrate benefit of adding low-dose oral methotrexate or every other month IV methylprednisolone to interferon beta-1a in relapsing-remitting multiple sclerosis.
Cohen
J A
JA
Mellen Center U-10, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. cohenj@ccf.org
Imrey
P B
PB
Calabresi
P A
PA
Edwards
K R
KR
Eickenhorst
T
T
Felton
W L
WL
Fisher
E
E
Fox
R J
RJ
Goodman
A D
AD
Hara-Cleaver
C
C
Hutton
G J
GJ
Mandell
B F
BF
Scott
T F
TF
Zhang
H
H
Apperson-Hansen
C
C
Beck
G J
GJ
Houghtaling
P L
PL
Karafa
M T
MT
Stadtler
M
M
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D003299:Cooperative Behavior; D003627:Data Interpretation, Statistical; D004185:Disability Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D018579:Patient Selection; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D016899:Interferon-beta; D008775:Methylprednisolone; D000068556:Interferon beta-1a; D008727:Methotrexate