Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study
نویسندگان
چکیده
OBJECTIVE To evaluate the effects of oral delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) on MRI lesion activity and load, atrophy, and magnetization transfer ratio (MTR) measures from the Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM) study. METHODS CONFIRM was a 2-year, placebo-controlled study of the efficacy and safety of DMF 240 mg twice (BID) or 3 times daily (TID) in 1,417 patients with relapsing-remitting multiple sclerosis (RRMS); subcutaneous glatiramer acetate 20 mg once daily was included as an active reference comparator. The number and volume of T2-hyperintense, T1-hypointense, and gadolinium-enhancing (Gd+) lesions, as well as whole brain volume and MTR, were assessed in 681 patients (MRI cohort). RESULTS DMF BID and TID produced significant and consistent reductions vs placebo in the number of new or enlarging T2-hyperintense lesions and new nonenhancing T1-hypointense lesions after 1 and 2 years of treatment and in the number of Gd+ lesions at week 24, year 1, and year 2. Lesion volumes were also significantly reduced. Reductions in brain atrophy and MTR changes with DMF relative to placebo did not reach statistical significance. CONCLUSIONS The robust effects on MRI active lesion counts and total lesion volume in patients with RRMS demonstrate the ability of DMF to exert beneficial effects on inflammatory lesion activity in multiple sclerosis, and support DMF therapy as a valuable new treatment option in RRMS. CLASSIFICATION OF EVIDENCE This study provides Class I evidence of reduction in brain lesion number and volume, as assessed by MRI, over 2 years of delayed-release DMF treatment.
منابع مشابه
Efficacy and safety of delayed-release dimethyl fumarate in patients newly diagnosed with relapsing–remitting multiple sclerosis (RRMS)
BACKGROUND Delayed-release dimethyl fumarate (DMF) demonstrated efficacy and safety in the Phase 3 DEFINE and CONFIRM trials. OBJECTIVE To evaluate delayed-release DMF in newly diagnosed relapsing-remitting multiple sclerosis (RRMS) patients, in a post-hoc analysis of integrated data from DEFINE and CONFIRM. METHODS Patients included in the analysis were diagnosed with RRMS within 1 year pr...
متن کاملLong-term effects of delayed-release dimethyl fumarate in multiple sclerosis: Interim analysis of ENDORSE, a randomized extension study
BACKGROUND Delayed-release dimethyl fumarate (DMF) demonstrated strong efficacy and a favorable benefit-risk profile for patients with relapsing-remitting multiple sclerosis (RRMS) in phase 3 DEFINE/CONFIRM studies. ENDORSE is an ongoing long-term extension of DEFINE/CONFIRM. OBJECTIVE We report efficacy and safety results of a 5-year interim analysis of ENDORSE (2 years DEFINE/CONFIRM; minim...
متن کاملEfficacy of delayed-release dimethyl fumarate in relapsing-remitting multiple sclerosis: integrated analysis of the phase 3 trials
OBJECTIVE Obtain a more precise estimate of the efficacy of delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) in relapsing multiple sclerosis (MS) and examine the consistency of DMF's effects across patient subgroups stratified by baseline demographic and disease characteristics. METHODS A prespecified integrated analysis of the randomized, double-blind, placebo-cont...
متن کاملEffect of delayed‐release dimethyl fumarate on no evidence of disease activity in relapsing–remitting multiple sclerosis: integrated analysis of the phase III DEFINE and CONFIRM studies
BACKGROUND AND PURPOSE Significant effects on clinical/neuroradiological disease activity have been reported in patients with relapsing-remitting multiple sclerosis treated with delayed-release dimethyl fumarate (DMF) in phase III DEFINE/CONFIRM trials. We conducted a post hoc analysis of integrated data from DEFINE/CONFIRM to evaluate the effect of DMF on achieving no evidence of disease activ...
متن کاملP120: Efficacy and Safety of Dimethyl Fumarate Treatment in Relapsing-Remitting Multiple Sclerosis
Multiple sclerosis (MS) is a chronic autoimmune disorder of central nervous system. This demyelinating disease affects more than 2.3 million people world wild. Most of patients are young adult. The most common type of MS is relapsing remitting multiple sclerosis (RRMS). However there is no cure, available modifying therapies has revolutionized the care of patients with RRMS. Interferon (IFN) be...
متن کاملDelayed-release dimethyl fumarate and disability assessed by the Multiple Sclerosis Functional Composite: Integrated analysis of DEFINE and CONFIRM
The effect of delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) on the Multiple Sclerosis Functional Composite (MSFC) was assessed using integrated Phase 3 DEFINE and CONFIRM data. Patients treated with DMF (n = 769) demonstrated significant superiority on the MSFC, and each component, compared with placebo (n = 771) over two years: mean change for DMF vs placebo was 0...
متن کامل