TY - JOUR
T1 - PRISMS
T2 - The story of a pivotal clinical trial series in multiple sclerosis
AU - Cohen, Bruce A.
AU - Rivera, Victor M.
N1 - Funding Information:
Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewer 1 has disclosed receiving research grant funding from Genzyme, Genentech, Alexion and acting as a consultant/adviser to Novartis. Peer Reviewer 2 has disclosed no relevant financial relationships.
Funding Information:
B.C. has disclosed receiving funding from Biogen-Idec, BMS Medical/Lilly, EMD Serono, Inc., the National Institutes of Health, Novartis, Sanofi-Aventis and Teva Neuroscience; he has carried out consultancy work for Accorda, Bayer, Biogen-Idec, EMD Serono, Inc., Sanofi-Aventis and Teva Neuroscience and has received honoraria for speaking from Bayer, Biogen-Idec, EMD Serono, Inc., Novartis and Teva Neuroscience; he holds common stock in Abbott Laboratories and CVS Caremark. V.R. has disclosed receiving funding and honoraria from Biogen-Idec, Bayer Healthcare, EMD Serono, Inc., Teva Neuroscience, NMSS, Consortium of MS Centers and Stendhal Neurosciences; he has also carried out consultancy work for Novartis.
PY - 2010/4
Y1 - 2010/4
N2 - Background: The PRISMS (Prevention of Relapses and disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) study was initiated in 1994, at which time there were few disease-modifying drugs for multiple sclerosis (MS). The PRISMS series of studies has since provided up to 8 years of clinical, magnetic resonance imaging (MRI), safety, and immunogenicity data on the use of subcutaneous (sc) interferon (IFN) beta-1a in patients with relapsingremitting MS. This review is the first collation of all these data in one article, with a look ahead to the next generation of studies involving the new formulation of sc IFN beta-1a. Methods: Published efficacy, safety, and immunogenicity data, in terms of prospectively defined endpoints and later post hoc analyses, from years 18 of the PRISMS series are summarized and collated for the first time. Some of the studies of sc IFN beta-1a that evolved from the PRISMS studies are also discussed. Findings: In the 2-year, double-blind, randomized, placebo-controlled study, IFN beta-1a (22 or 44mcg three times weekly [tiw]) was associated with significantly lower relapse rates, disability progression, and MRI burden of disease compared with placebo (p≤0.05). Subsequently, in the 2-year extension, patients previously receiving placebo were re-randomized to active treatment, and a further 2 years of open-label treatment confirmed good long-term safety and therapeutic efficacy. Follow-up visits at years 7 or 8 (68.2 of initial population) demonstrated a continued benefit for patients originally randomized to the 44-mcg dose compared with those receiving the 22-mcg dose or whose treatment had been delayed by 2 years. Neutralizing antibodies were more common in patients receiving the 22-mcg dose and attenuated treatment efficacy during years 14. Conclusion: Class I and long-term data from PRISMS support the use of sc IFN beta-1a tiw as a first-line treatment for MS, as evidenced by sustained efficacy rates, acceptable safety profiles, and high patient retention rates.
AB - Background: The PRISMS (Prevention of Relapses and disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) study was initiated in 1994, at which time there were few disease-modifying drugs for multiple sclerosis (MS). The PRISMS series of studies has since provided up to 8 years of clinical, magnetic resonance imaging (MRI), safety, and immunogenicity data on the use of subcutaneous (sc) interferon (IFN) beta-1a in patients with relapsingremitting MS. This review is the first collation of all these data in one article, with a look ahead to the next generation of studies involving the new formulation of sc IFN beta-1a. Methods: Published efficacy, safety, and immunogenicity data, in terms of prospectively defined endpoints and later post hoc analyses, from years 18 of the PRISMS series are summarized and collated for the first time. Some of the studies of sc IFN beta-1a that evolved from the PRISMS studies are also discussed. Findings: In the 2-year, double-blind, randomized, placebo-controlled study, IFN beta-1a (22 or 44mcg three times weekly [tiw]) was associated with significantly lower relapse rates, disability progression, and MRI burden of disease compared with placebo (p≤0.05). Subsequently, in the 2-year extension, patients previously receiving placebo were re-randomized to active treatment, and a further 2 years of open-label treatment confirmed good long-term safety and therapeutic efficacy. Follow-up visits at years 7 or 8 (68.2 of initial population) demonstrated a continued benefit for patients originally randomized to the 44-mcg dose compared with those receiving the 22-mcg dose or whose treatment had been delayed by 2 years. Neutralizing antibodies were more common in patients receiving the 22-mcg dose and attenuated treatment efficacy during years 14. Conclusion: Class I and long-term data from PRISMS support the use of sc IFN beta-1a tiw as a first-line treatment for MS, as evidenced by sustained efficacy rates, acceptable safety profiles, and high patient retention rates.
KW - Disability
KW - Interferon beta-1a
KW - Magnetic resonance imaging
KW - Neutralizing antibody
KW - Relapse
KW - Relapsing
KW - Remitting multiple sclerosis
KW - Safety
UR - http://www.scopus.com/inward/record.url?scp=77949518424&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77949518424&partnerID=8YFLogxK
U2 - 10.1185/03007991003604018
DO - 10.1185/03007991003604018
M3 - Review article
C2 - 20121658
AN - SCOPUS:77949518424
SN - 0300-7995
VL - 26
SP - 827
EP - 838
JO - Current Medical Research and Opinion
JF - Current Medical Research and Opinion
IS - 4
ER -