250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study.
BACKGROUND
The aim of the Betaferon Efficacy Yielding Outcomes of a New Dose (BEYOND) trial was to compare the efficacy, safety, and tolerability of 250 microg or 500 microg interferon beta-1b with glatiramer acetate for treating relapsing-remitting multiple sclerosis.


METHODS
Between November, 2003, and June, 2005, 2447 patients with relapsing-remitting multiple sclerosis were screened and 2244 patients were enrolled in this prospective, multicentre, randomised trial. Patients were randomly assigned 2:2:1 by block randomisation with regional stratification to receive one of two doses of interferon beta-1b (250 microg or 500 microg) subcutaneously every other day or 20 mg glatiramer acetate subcutaneously every day. The primary outcome was relapse risk, defined as new or recurrent neurological symptoms separated by at least 30 days from the preceding event and that lasted at least 24 h. Secondary outcomes were progression on the expanded disability status scale (EDSS) and change in T1-hypointense lesion volume. Clinical outcomes were assessed quarterly for 2.0-3.5 years; MRI was done at screening and annually thereafter. Analysis was by per protocol. This study is registered, number NCT00099502.


RESULTS
We found no differences in relapse risk, EDSS progression, T1-hypointense lesion volume, or normalised brain volume among treatment groups. Flu-like symptoms were more common in patients treated with interferon beta-1b (p<0.0001), whereas injection-site reactions were more common in patients treated with glatiramer acetate (p=0.0005). Patient attrition rates were 17% (153 of 888) on 250 microg interferon beta-1b, 26% (227 of 887) on 500 microg interferon beta-1b, and 21% (93 of 445) for glatiramer acetate.


CONCLUSIONS
500 microg interferon beta-1b was not more effective than the standard 250 microg dose, and both doses had similar clinical effects to glatiramer acetate. Although interferon beta-1b and glatiramer acetate had different adverse event profiles, the overall tolerability to both drugs was similar.


BACKGROUND
Bayer HealthCare Pharmaceuticals.
O'Connor
Paul
P
St Michael's Hospital, Toronto, Canada. oconnorp@smh.toronto.on.ca
Filippi
Massimo
M
Arnason
Barry
B
Comi
Giancarlo
G
Cook
Stuart
S
Goodin
Douglas
D
Hartung
Hans-Peter
HP
Jeffery
Douglas
D
Kappos
Ludwig
L
Boateng
Francis
F
Filippov
Vitali
V
Groth
Maria
M
Knappertz
Volker
V
Kraus
Christian
C
Sandbrink
Rupert
R
Pohl
Christoph
C
Bogumil
Timon
T
O'Connor
P
P
Filippi
M
M
Arnason
B
B
Cook
S
S
Goodin
D
D
Hartung
H-P
HP
Harung
H-P
HP
Kappos
L
L
Jeffery
D
D
Comi
G
G
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D010455:Peptides / Q000627:therapeutic use*; D055815:Young Adult
D007155:Immunologic Factors; D010455:Peptides; D000068576:Interferon beta-1b; D000068717:Glatiramer Acetate; D016899:Interferon-beta