a-t 2016; 47: 49

Access to the file confirmed PML (progressive multifocal leukoencephalopathy) under dimethyl fumarate (TECFIDERA) with moderate lymphopenia: For weeks we have tried to get further details or at least confirmation from the German and the European Medicines Agency about a PML case reported on medical information portals in relation to a female patient with multiple sclerosis who had taken dimethyl fumarate (TECFIDERA) and developed only moderate lymphopenia (grade 2) (a-t 2016; 47: 24, 39-40). Clarification has now been given but only after our request to the Federal Institute for Drugs and Medical Devices (BfArM) to access the file in accordance with the Freedom of Information Act. According to the adverse event report from the USA, the affected patient had actually had previously only a moderate lymphopenia with lymphocyte counts ranging from 600/µl to 700/µl for at least 9.5 months. In the USA, the disease was confirmed as PML with no indication of other potential trigger factors (1). The case and the assessment is known in Europe since early November 2015, i.e. a few days after the EMA completed its risk assessment procedure of dimethyl fumarate but more than two weeks before the provider, Biogen, sent out the Dear Doctor letter. In the correspondence to doctors, merely a note was added that diseases confirmed up to 30 October 2015 were being considered (2). The BfArM justified this action on the grounds that the risk-related information should be made available as soon as possible (3) - a rather weak argument given the timing involved (the first case of PML with TECFIDERA had emerged more than a year earlier). Even after that the public was not informed that life-threatening PML could develop not only with persistent severe lymphopenia under dimethyl fumarate - as was actually anticipated based on relevant reports about the fumaric acid mixture FUMADERM (a t 2015; 46: 101-2) - but also with a less pronounced fall in the lymphocyte count. Why the authorities failed to inform about the new risk constellation of their own accord or on request is unknown. Unfortunately, the Freedom of Information Act is not shedding light on the reasons behind this disinformation -Ed.

  1 BfArM: letter dated 26 April 2016
  2 Biogen: Rote-Hand-Brief [Dear Doctor letter] dated 23 Nov. 2015; http://www.akdae.de/Arzneimittelsicherheit/RHB/Archiv/2015/20151123.pdf
  3 BfArM: letter dated 2 Febr. 2016

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