This case is not exactly new – to be precise, the news came out in October 2014 – nevertheless, I keep hearing inquiries about the situation, which is why I would like to briefly comment on the case again. In October 2014, we sadly had to learn that a patient who was treated with Tecfidera within the extension study of the approval studies (ENDORSE) developed PML and died from the consequences of this disease. The question now is to what extent this case changes our assessment of Tecfidera in the treatment of relapsing MS.Basically, nothing certainly changes in the assessment of the indication and the effectiveness of Tecfidera. The drug is a valuable oral alternative in the basic therapy of MS and has a good clinical effectiveness and an acceptable safety and tolerability profile. What will change, however, are the requirements for monitoring patients treated with Tecfidera. Originally, the technical information stated that it is sufficient to check the blood count of patients with Tecfidera at six-month intervals.
It has now become known that the patient showed a significant reduction in the number of lymphocytes to below 500/µl for years before developing PML. Since there has also been a prolonged lymphocyte suppression in the few cases of PML associated with Fumaderm (the fumaric acid preparation that has been used to treat psoriasis since 1994), it can be assumed that this is a decisive risk factor for developing PML under treatment with fumaric acid. For this reason, a regular (6 – 8 weekly) check of the differential blood count must be carried out in the future during therapy with Tecfidera – as the German therapy guidelines have recommended since the drug was approved.
If the lymphocytes fall below a critical threshold in these checks, this development must be closely monitored. In the event that a persistent reduction below the critical limit values is shown, I believe an alternative therapy should be chosen. There is no reason to panic in such a case. Previous experience teaches us that lymphocyte suppression probably needs to persist for a longer period before an opportunistic infection occurs. So if you react in time, there is enough time and calm for a considered change of therapy.
From the studies, we know that about 6 – 8% of patients develop a pronounced lymphopenia under Tecfidera, without it being predictable. For this group of patients, Tecfidera does not represent a sensible MS therapy. Given the large number of available alternatives, switching should not pose a problem.
Otherwise, from my point of view, there are no further consequences from this first PML case under Tecfidera. Of course, people will now be very vigilant and watch how the further development of the active ingredient in clinical use is.
