Dimethyl fumarate (Tecfidera®) has established itself as a first-line therapy for the treatment of multiple sclerosis. The availability of an effective oral therapy with a favorable side effect profile has expanded the possibilities of MS therapy.Uncertainty arose after four cases of progressive multifocal leukoencephalopathy (PML) occurred under therapy with Tecfidera. This is a sporadic occurrence, which can occur with many immunotherapies, in contrast to therapy with Natalizumab (Tysabri®) . For comparison: currently, approximately 170,000 patients worldwide are being treated with Dimethyl fumarate and 4 PML cases have occurred worldwide, with Natalizumab currently treating 150,000 patients worldwide and over 600 PML cases are known. We are therefore talking about a completely different order of magnitude with Tysabri, which of course also requires different risk management.
Nevertheless, it is of high interest to learn more about the PML cases under Tecfidera and to identify risk factors. Thus, in three of the four PML cases under Tecfidera, a prolonged lymphocytopenia was observed in advance, i.e. a drop in lymphocytes (a subgroup of white blood cells in the differential blood count) in peripheral blood to < 500/µl. The fourth case did not have such pronounced lymphocytopenia, but here too a fall below the lower normal limits of lymphocyte values could be demonstrated.
Accordingly, prolonged lymphopenia (> 6 months) is the only identifiable risk factor for the development of PML under Tecfidera. Therefore, following the reassessment of drug safety by the European Medicines Agency (EMA), regular monitoring of the differential blood count under Tecfidera was also prescribed.
At the current congresses, it was now communicated that the risk of long-lasting lymphopenia exists primarily if lymphocyte values below 500/µl in peripheral blood are measured in the first 6 months after the start of therapy. Especially at the beginning of a Tecfidera therapy it is therefore worthwhile to observe whether there is a rapid drop in lymphocytes. In patients who show such a rapid drop in lymphocytes and whose values remain low in the course, an alternative therapy should be sought.
Patients who have stable lymphocyte values in the first months that are up to 30% below the baseline values probably do not have a significant risk potential in the further course. In addition, a single low measured lymphocyte value should not have a direct consequence, but should first be controlled. Until further knowledge is available, the consistent monitoring of lymphocytes, especially in the initial phase of therapy, seems to be an appropriate means to identify patients at increased risk.
