ClinicSpeak: How quickly does DMF (Tecfidera) work

How bold is Biogen-Idec? Switching from natalizumab to DMF. #ClinicSpeak #MSResearch #MSBlog

"How quickly a DMT works may be important. This post-hoc (after the event) analysis of the dimethyl fumarate (DMF, Tecfidera) phase 3 studies shows it working within 24 weeks. Is this quick enough? It may not be for MSers with highly active MS or those switching from natalizumab. DMF does not look like it prevents the rebound we see in approximately a third of MSers after stopping natalizumab. In comparison fingolimod when started within 4 weeks of the last natalizumab infusion stops most rebound. Is this because DMF is less effective than fingolimod or is it because DMF needs more time to start working? A simple experiment will be to take natalizumab-treated MSers and start them on DMF 3 months before their last infusion, i.e. overlap the treatments. This would mean that DMF has had 6 months to start working by the time natalizumab is out of the system. If this strategy prevents rebound post-natalizumab then its is not efficacy that is in doubt, but the time for DMF to have it maximum therapeutic effect. I wonder if Biogen-Idec would be interested in doing this study? I have mentioned it to them already but have had no feedback. I think this study should be done as it will provide an important bit of information that we require to help us make decisions regarding the sequencing of DMTs."



Epub: Kappos et al. Time course of clinical and neuroradiological effects of delayed-release dimethyl fumarate in multiple sclerosis. Eur J Neurol. 2015. doi: 10.1111/ene.12624.

BACKGROUND AND PURPOSE: Delayed-release dimethyl fumarate (DMF, also known as gastro-resistant DMF), demonstrated efficacy and safety in relapsing-remitting multiple sclerosis in the 2-year, randomized, placebo-controlled, phase 3 DEFINE and CONFIRM trials. A post hoc analysis of integrated data from DEFINE and CONFIRM was conducted to determine the temporal profile of the clinical and neuroradiological effects of DMF.

METHODS: Eligible patients were randomized to receive placebo, DMF 240 mg twice (BID) or three times (TID) daily or glatiramer acetate (GA; reference comparator; CONFIRM only) for up to 96 weeks. Patients in the GA group were excluded from this analysis.

RESULTS: A total of 2301 patients were randomized and received treatment with placebo (n = 771) or DMF BID (n = 769) or TID (n = 761). DMF significantly reduced the annualized relapse rate beginning in weeks 0-12 (BID, P = 0.0159; TID, P = 0.0314); the proportion of patients relapsed beginning at week 10 (BID, P = 0.0427) and week 12 (TID, P = 0.0451); and the proportion of patients with 12-week confirmed disability progression beginning at week 62 (BID, P = 0.0454) and week 72 (TID, P = 0.0399), compared with placebo. These effects were sustained throughout the 2-year study period. DMF significantly reduced the odds of having a higher number of gadolinium-enhancing lesions by 88% (BID) and 75% (TID) and the mean number of new or enlarging T2 lesions by 72% (BID) and 67% (TID), from the first post-baseline magnetic resonance imaging assessment at 24 weeks (all P < 0.0001 versus placebo).

CONCLUSIONS: In phase 3 clinical trials, DMF demonstrated rapid and sustained clinical and neuroradiological efficacy in relapsing-remittingmultiple sclerosis.

CoI: multiple, I am a co-author on this study

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