Oral interferon beta-1a in relapsing-remitting multiple sclerosis: a double-blind randomized study.
BACKGROUND
Interferon beta (IFNB) is available in parenteral formulations for treatment of multiple sclerosis (MS). The purpose of this study was to evaluate safety, tolerability and effects on MRI lesions of three different doses of oral IFNB-1a compared with placebo over six months in relapsing-remitting (RR) MS patients.


METHODS
In this multicenter; double-blind randomized trial, RR-MS patients received 0.06, 0.6 or 6 million international units (MIU) IFNB-1a or placebo every other day for up to six months. Gadolinium DTPA-enhanced brain MRI scans were performed at screening and monthly during treatment. The primary variable was the cumulative number of newly active lesions. Secondary variables included volume of enhancing lesions on T1-weighted images each month and lesion volume on T2-weighted images at months three and six. Safety measures included adverse events, laboratory variables, vital signs, ECG, physical examination, EDSS and number of relapses. Neopterin was measured in 21 patients and neutralizing antibodies in 24 patients.


RESULTS
Of 194 screened patients, 173 were randomized (42-44 patients per group) in 15 centers. Median cumulative numbers of newly active lesions over six months were 4.0 in the placebo and 0.6 MIU groups, compared with 7.5 and 9.0 in the 0.06 and 6 MIU groups (no significant differences). Secondary efficacy endpoints showed small and inconsistent differences between groups. Adverse events showed no notable group differences. Approximately two-thirds of patients in each group remained relapse free. No patients showed neutralizing antibodies. Neopterin levels were comparable between groups.


CONCLUSIONS
Oral IFNB-1a showed neither beneficial effects in RRMS nor any systemic biological effects. Treatment was safe and well tolerated.
Polman
C
C
Department of Neurology, Free University Medical Center, de Boelelaan 1117, NL-1007 MB Amsterdam, The Netherlands. ch.polman@vumc.nl
Barkhof
F
F
Kappos
L
L
Pozzilli
C
C
Sandbrink
R
R
Dahlke
F
F
Jakobs
P
P
Lorenz
A
A
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D016899:Interferon-beta; D000068556:Interferon beta-1a