TY - JOUR
T1 - A one-year prospective, randomized, placebo-controlled, quadruple-blinded, phase II safety pilot trial of combination therapy with interferon beta-1a and mycophenolate mofetil in early relapsing-remitting multiple sclerosis (TIME MS)
AU - Remington, Gina M.
AU - Treadaway, Katherine
AU - Frohman, Teresa
AU - Salter, Amber
AU - Stuve, Olaf
AU - Racke, Michael K.
AU - Hawker, Kathleen
AU - Agosta, Federica
AU - Sormani, Maria Pia
AU - Filippi, Massimo
AU - Frohman, Elliot M.
PY - 2010/1
Y1 - 2010/1
N2 - Background: Mycophenolate mofetil (MMF) is an oral DNA base synthesis inhibitor with immunomodulatory effects on B cells, T cells, and macrophages. Objective: To conduct a safety and tolerability pilot study of interferon beta-1a (IFN-b1a) in combination with either placebo or oral MMF in multiple sclerosis (MS). Methods: Twenty-four treatment-naïve R-RMS patients participated in a one-year prospective, placebo-controlled, blinded, safety pilot clinical trial. Every patient injected weekly intramuscular interferon beta-1a. The cohort was then randomized (1 : 1) to either active oral MMF or identical-appearing placebo tablets. Clinical evaluations were assessed every 3 months, along with brain MRI scans performed at baseline and repeated every 60 days for one year. Comprehensive laboratory assessments were monitored for safety, along with adverse events. Results: In this small pilot investigation, no differences were identified between the two treatment groups with respect to patient-reported adverse events, MRI metrics, or laboratory abnormalities. Notwithstanding these observations, and the limited number of patients treated, trends appeared to favor the combination therapy regimen. Conclusions: The combination treatment regimen of interferon beta-1a and MMF appeared to be well tolerated in this pilot study. Despite the small sample size, therapeutic trends were observed in favor of combination therapy. An adequately powered controlled trial of MMF in MS appears warranted.
AB - Background: Mycophenolate mofetil (MMF) is an oral DNA base synthesis inhibitor with immunomodulatory effects on B cells, T cells, and macrophages. Objective: To conduct a safety and tolerability pilot study of interferon beta-1a (IFN-b1a) in combination with either placebo or oral MMF in multiple sclerosis (MS). Methods: Twenty-four treatment-naïve R-RMS patients participated in a one-year prospective, placebo-controlled, blinded, safety pilot clinical trial. Every patient injected weekly intramuscular interferon beta-1a. The cohort was then randomized (1 : 1) to either active oral MMF or identical-appearing placebo tablets. Clinical evaluations were assessed every 3 months, along with brain MRI scans performed at baseline and repeated every 60 days for one year. Comprehensive laboratory assessments were monitored for safety, along with adverse events. Results: In this small pilot investigation, no differences were identified between the two treatment groups with respect to patient-reported adverse events, MRI metrics, or laboratory abnormalities. Notwithstanding these observations, and the limited number of patients treated, trends appeared to favor the combination therapy regimen. Conclusions: The combination treatment regimen of interferon beta-1a and MMF appeared to be well tolerated in this pilot study. Despite the small sample size, therapeutic trends were observed in favor of combination therapy. An adequately powered controlled trial of MMF in MS appears warranted.
KW - CellCept
KW - immunosuppression
KW - mycophenolate mofetil
KW - relapsing-remitting multiple sclerosis
KW - treatment naïve
UR - http://www.scopus.com/inward/record.url?scp=77953453035&partnerID=8YFLogxK
U2 - 10.1177/1756285609355851
DO - 10.1177/1756285609355851
M3 - Article
C2 - 21180632
AN - SCOPUS:77953453035
SN - 1756-2856
VL - 3
SP - 3
EP - 13
JO - Therapeutic Advances in Neurological Disorders
JF - Therapeutic Advances in Neurological Disorders
IS - 1
ER -