Havrdova E, Giovannoni G, Gold R, Fox RJ, Kappos L, Phillips JT, Okwuokenye M, Marantz JL.
Effect 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.
Eur J Neurol. 2017 . doi: 10.1111/ene.13272. [Epub ahead of print]
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 activity (NEDA) in patients with relapsing-remitting multiple sclerosis.
METHODS: The analysis included patients randomized to DMF 240 mg twice daily, placebo or glatiramer acetate (CONFIRM only) for ≤2 years. A time-to-event method was used to estimate the percentage of patients achieving NEDA. Clinical NEDA (no relapses/no 12-week confirmed disability progression) was analysed in the intention-to-treat (ITT) population. Neuroradiological (no new/newly enlarging T2 hyperintense lesions/no gadolinium-enhancing lesions) and overall NEDA (clinical and neuroradiological NEDA) were analysed in the magnetic resonance imaging (MRI) cohort.
RESULTS:The ITT and MRI populations comprised 1540 and 692 patients, respectively. The percentage of patients with clinical NEDA (ITT population) and neuroradiological NEDA (MRI cohort) was higher with DMF versus placebo over 2 years [clinical NEDA: 38.9% relative reduction; hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.52-0.72; P < 0.0001; neuroradiological NEDA: 40.0% relative reduction; HR, 0.60; 95% CI, 0.49-0.73; P < 0.0001]. The percentage of patients achieving overall NEDA (MRI cohort) was also higher with DMF (26%) versus placebo (12%) over 2 years, with a relative risk reduction of 42.7% (HR, 0.57; 95% CI, 0.48-0.69; P < 0.0001).
CONCLUSIONS:A significantly higher percentage of patients treated with DMF achieved NEDA status over 2 years compared with placebo.
Effect 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.
Eur J Neurol. 2017 . doi: 10.1111/ene.13272. [Epub ahead of print]
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 activity (NEDA) in patients with relapsing-remitting multiple sclerosis.
METHODS: The analysis included patients randomized to DMF 240 mg twice daily, placebo or glatiramer acetate (CONFIRM only) for ≤2 years. A time-to-event method was used to estimate the percentage of patients achieving NEDA. Clinical NEDA (no relapses/no 12-week confirmed disability progression) was analysed in the intention-to-treat (ITT) population. Neuroradiological (no new/newly enlarging T2 hyperintense lesions/no gadolinium-enhancing lesions) and overall NEDA (clinical and neuroradiological NEDA) were analysed in the magnetic resonance imaging (MRI) cohort.
RESULTS:The ITT and MRI populations comprised 1540 and 692 patients, respectively. The percentage of patients with clinical NEDA (ITT population) and neuroradiological NEDA (MRI cohort) was higher with DMF versus placebo over 2 years [clinical NEDA: 38.9% relative reduction; hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.52-0.72; P < 0.0001; neuroradiological NEDA: 40.0% relative reduction; HR, 0.60; 95% CI, 0.49-0.73; P < 0.0001]. The percentage of patients achieving overall NEDA (MRI cohort) was also higher with DMF (26%) versus placebo (12%) over 2 years, with a relative risk reduction of 42.7% (HR, 0.57; 95% CI, 0.48-0.69; P < 0.0001).
CONCLUSIONS:A significantly higher percentage of patients treated with DMF achieved NEDA status over 2 years compared with placebo.
This is one of ProfG’s and you can read the level of NEDA with DMF is better than with placebo, but not as good as reported with some other DMT.
CoI Prof G Multiple.
I've been on tecfidera for a year and have new lession so my neurologist recommends I take alemtuzumab or natalizumab. I've opted for alemtuzumab. Given it may cause 2nd autoimmunity. But nothing is worse than living with ms so no brainer for me (pardon the pun ) since daclizumab is now available shouldn't that be the first line treatment with 45% achieving NEDA? Compared 26%?
I remember before licencing DMF was mentioned 'the drug which cannibalize Natalizumab'. Now it is a simple first line drug with moderate efficacy so not highly or very highly effective…
In this pod podcast they talk about Neda in 7 years being treated with dmts guess what are the results?
7% of the patients remain Neda ….7% at 7 years
http://jamanetwork.com/learning/audio-player/8611564?resultClick=3
Interview with Howard L. Weiner, MD, author of Evaluation of No Evidence of Disease Activity in a 7-Year Longitudinal Multiple Sclerosis Cohort, and Michael K. Racke, MD, author of Is No Evidence of Disease Activity a Realistic Goal for Patients With Multiple Sclerosis?