FDA rules on Tecfidera-associated lymphopaenia and PML #ClinicSpeak #MSBlog #MSResearch
"The FDA has acknowledged the PML risk associated with DMF (dimethyl fumarate) therapy in a the following highlights of prescribing information. I note they have chosen 0.5 x 10^9/L, or 500/mm^3, as their threshold for interrupting DMF therapy. I can only assume this based on data presented to them by Biogen-Idec on the safety of DMF (Tecfidera) and the observation that the lymphopaenia is probably reversible. The data on the latter is quite limited at present; all I have is data from a poster presented at ECTRIMS in 2013 (see below)."
"Does this mean that if you remain on DMF and never have a lymphocyte count below 500 you are protected from getting PML? I suspect not. We cannot be sure that the risk of PML is not associated with some qualitative deficit in lymphocyte function that is not reflected in the absolute, or total, lymphocyte count. We will need to wait and see if any more cases of PML emerge in DMF-treated MSers and people with psoriasis and whether PML occurs with a normal lymphocyte count. The caveat being carry-over PML from natalizumab; it may be very difficult to counteract the latter and hence we can't blame DMF for this."
"The position the FDA has taken seems reasonable and hence should not affect how we use and prescribe DMF."
Figure 3 is from a poster presented at ECTRIMS 2013: Fox et al. Lymphocyte Count Reductions in Relapsing-Remitting Multiple Sclerosis (RRMS) Patients Treated With Oral BG-12 (dimethyl fumarate): Integrated Analysis of the Placebo-Controlled Studies. ECTRIMS 2013:P1018.
Labels: ClinicSpeak, DMF, FDA, PML, PML Risk