Randomized study of interferon beta-1a, low-dose azathioprine, and low-dose corticosteroids in multiple sclerosis.
BACKGROUND
Studies evaluating interferon beta (IFNbeta) for multiple sclerosis (MS) showed only partial efficacy. In many patients, IFNbeta does not halt relapses or disability progression. One strategy to potentially enhance efficacy is to combine IFNbeta with classical immunosuppressive agents, such as azathioprine (AZA) or corticosteroids, commonly used for other autoimmune disorders.


OBJECTIVE
The Avonex-Steroids-Azathioprine study was placebo-controlled trial and evaluated efficacy of IFNbeta-1a alone and combined with low-dose AZA alone or low-dose AZA and low-dose corticosteroids as initial therapy.


METHODS
A total of 181 patients with relapsing-remitting MS (RRMS) were randomized to receive IFNbeta-1a 30 microg intramuscularly (IM) once weekly, IFNbeta-1a 30 microg IM once weekly plus AZA 50 mg orally once daily, or IFNbeta-1a 30 microg IM once weekly plus AZA 50 mg orally once daily plus prednisone 10 mg orally every other day. The primary end point was annualized relapse rate (ARR) at 2 years. Patients were eligible for enrollment in a 3-year extension.


RESULTS
At 2 years, adjusted ARR was 1.05 for IFNbeta-1a, 0.91 for IFNbeta-1a plus AZA, and 0.73 for combination. The cumulative probability of sustained disability progression was 16.8% for IFNbeta-1a, 20.7% for IFNbeta-1a plus AZA, and 17.5% for combination. There were no statistically significant differences among groups for either measure at 2 and 5 years. Percent T2 lesion volume change at 2 years was significantly lower for combination (+14.5%) versus IFNbeta-1a alone (+30.3%, P < 0.05). Groups had similar safety profiles.


CONCLUSIONS
In IFNbeta-naïve patients with early active RRMS, combination treatment did not show superiority over IFNbeta-1a monotherapy.
Havrdova
E
E
Department of Neurology, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic. eva.havrdova@gmail.com
Zivadinov
R
R
Krasensky
J
J
Dwyer
M G
MG
Novakova
I
I
Dolezal
O
O
Ticha
V
V
Dusek
L
L
Houzvickova
E
E
Cox
J L
JL
Bergsland
N
N
Hussein
S
S
Svobodnik
A
A
Seidl
Z
Z
Vaneckova
M
M
Horakova
D
D
D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D001284:Atrophy; D001379:Azathioprine / Q000008:administration & dosage* / Q000009:adverse effects; D001921:Brain / Q000473:pathology; D004185:Disability Evaluation; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007273:Injections, Intramuscular; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage* / Q000009:adverse effects; D008279:Magnetic Resonance Imaging; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D016899:Interferon-beta; D001379:Azathioprine; D011241:Prednisone; D000068556:Interferon beta-1a