At the start of June, the Federal Institute for Drugs and Medical Devices (BfArM) asked us to print a counter-statement on our article about progressive multifocal leukoencephalopathy (PML) in connection with the fumaric acid ester mixture FUMADERM in the May edition of arznei-telegramm (1). It serves no purpose insofar as it ignores the essential criteria of a counter-statement. However, we consider the contents of the letter interesting because they give an insight into how the authority thinks and operates. In response to our accusation of a lack of action in relation to risk minimisation measures that we escalated in the June a-t (a-t 2013; 44: 55), the BfArM states:

"Relevant publications on PML in connection with the use of FUMADERM appeared in the New England Journal of Medicine on 25 April 2013... Measures were implemented immediately in May 2013. The measures and their implementation are currently being arranged in coordination with the pharmaceutical company, so we are unable to make any specific comments to arznei-telegramm at this time...

To summarise, the accusation of a lack of action is therefore baseless and is rejected by the BfArM." (1)

However, the BfArM has been aware of reports of PML in connection with the fumaric acid ester mixture since at least 2009. These appear to have lurked in the database there until the a-t's enquiries in March 2013 and two publications in the New England Journal of Medicine in April 2013 highlighted the urgency of overdue risk-minimisation measures. The authorities acted "immediately" only in removing one of the suspected PML cases from their newly open-access database within a few days after its publication (c.f. a-t 2013; 44: 47-8). And they also appear to have had enough time left to prepare a counter-statement, whereas risk information for doctors and patients was still being awaited.

Not until 25 June 2013 did the supplier, biogen idec, finally issue a Dear Doctor Letter mentioning "three individual case reports of progressive multifocal leukoencephalopathy", one case of Kaposi's sarcoma and one report of nocardiosis in FUMADERM users "diagnosed with severe lymphopenia" (2). It remains to be seen whether or not it really is possible to "prevent" the risk of opportunistic infections, as claimed in the letter's heading, "by carrying out regular laboratory controls and adhering to other warnings". In addition, the Summary of Product Characteristics (SPC) of the fumaric acid ester mixture has not yet been updated - it is "being prepared" (2). On the company's home page, doctors will still find the 2012 version (!), according to which there is "no evidence to date" that the haematological changes lead to opportunistic infections (3)**. Furthermore, although a guide to administration of the treatment, which emphasises the "great long-term safety" of the product, does discuss in detail how to deal with gastrointestinal tolerability problems (4), not a word is said about the very common blood disorders. The Dear Doctor Letter is also nowhere to be found on the supplier's home page. Does this look like adequate risk management? - Ed.

1

BfArM: letter dated 7 June 2013; http://www.arznei-telegramm.de/blitz-pdf/Schreiben_des_BfArM_07062013.pdf

2

biogen idec: Dear Doctor Letter dated 25 June 2013 http://www.bfarm.de/SharedDocs/1_Downloads/DE/Pharmakovigilanz/ roteHandBriefe/2013/rhb-fumaderm.pdf?__blob=publicationFile

3

biogen idec: FUMADERM SPC, as at June 2012

4

biogen idec: Information for physicians on administering the treatment, http://www.psoriasis-support.de/fumaderm/arztinformation/therapiedurchfuehrung/content-129357.html (requires login, e.g. DocCheck)

*

Previous version published on 10 June 2013 as blitz-a-t

**

The version in the Fachinfo-Service of the Rote Liste Service GmbH (www.fachinfo.de) is actually dated Febr. 2009.