Long-term subcutaneous interferon beta-1a therapy in patients with relapsing-remitting MS.
OBJECTIVE
To conduct systematic long-term follow-up (LTFU) of patients in the Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis (PRISMS) study to provide up to 8 years of safety, clinical and MRI outcomes on subcutaneous (s.c.) interferon (IFN) beta-1a in relapsing-remitting multiple sclerosis (RRMS).


METHODS
The original cohort of 560 patients was randomized to IFNbeta-1a, 44 or 22 microg three times weekly (TIW) or to placebo; after 2 years, patients on placebo were rerandomized to active treatment and the blinded study continued for a further 4 years. The LTFU visit was scheduled 7 to 8 years after baseline.


RESULTS
LTFU was attended by 68.2% of the original PRISMS study cohort (382/560 patients). 72.0% (275/382) were still receiving IFNbeta-1a s.c. TIW. Patients originally randomized to IFNbeta-1a 44 microg s.c. TIW showed lower Expanded Disability Status Scale progression, relapse rate and T2 burden of disease up to 8 years compared with those in the late treatment group. Brain parenchymal volume did not show differences by treatment group. Overall, 19.7% of patients progressed to secondary progressive MS between baseline and LTFU (75/381). No new safety concerns were identified and treatment was generally well tolerated.


CONCLUSIONS
Despite the limitations inherent in any long-term study (for example, potential differences between returning and nonreturning patients), these results indicate that patients with relapsing-remitting multiple sclerosis can experience sustained benefit over many years from early interferon beta-1a subcutaneous therapy three times weekly compared with patients whose treatment is delayed. This effect was more apparent in the patients receiving the higher dose.
Kappos
L
L
University of Basel, Basel, Switzerland. lkappos@uhbs.ch
Traboulsee
A
A
Constantinescu
C
C
Erälinna
J-P
JP
Forrestal
F
F
Jongen
P
P
Pollard
J
J
Sandberg-Wollheim
M
M
Sindic
C
C
Stubinski
B
B
Uitdehaag
B
B
Li
D
D
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000473:pathology; D015331:Cohort Studies; D004185:Disability Evaluation; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous / Q000379:methods; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000473:pathology / Q000517:prevention & control*; D012189:Retrospective Studies; D055502:Secondary Prevention; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D016899:Interferon-beta; D000068556:Interferon beta-1a