In my previous post, I wrote about the basic importance of the small blood count and the differential blood count (“complete blood count”) – I therefore refer to this article for a better understanding of the post. I had announced that I would like to write about the practical significance of the blood count for individual MS medications and am now starting with dimethyl fumarate (Tecfidera) – because here, monitoring the blood count plays a major role, especially in the first year of therapy.Dimethyl fumarate is taken twice a day in tablet form and is a preparation that has increasingly become important for the initial therapy of mild and moderate MS disease courses. It is offered as an oral alternative to interferons or glatiramer acetate. Even though gastrointestinal discomfort can often occur at the start of therapy, dimethyl fumarate has a very acceptable side effect profile. The study data have shown hardly any serious complications with the drug, i.e., there were no safety signals from the different organ systems. Therefore, the fact that few cases (currently there are 5 cases) of progressive multifocal leukoencephalopathy (PML) were reported under therapy with dimethyl fumarate was a disappointment. It is always possible that opportunistic infections (such as PML) can occur during treatment with immunotherapeutics and considering the many thousands of patients treated worldwide, 5 cases are a small number in relation. Nevertheless, it is necessary to think about preventive measures.
Accordingly, it was an important observation that the patients affected by PML were older (> 55 years) and a significant and long-lasting lymphopenia had preceded the outbreak of PML. In almost all patients, the absolute lymphocyte count had even fallen below 500/µl over a longer period.
A long-lasting lymphopenia is thus (in addition to age) considered a risk factor for PML and the monitoring of lymphocyte counts under dimethyl fumarate is the only parameter that indicates a potential risk from opportunistic infections. Therefore, regular monitoring of the complete blood count with counting of lymphocytes when using dimethyl fumarate is of great importance and should be checked every 6 – 8 weeks, especially in the first year of therapy. We have now learned that a rapid drop in lymphocyte counts in the first weeks and months after starting dimethyl fumarate is particularly predisposing to long-lasting lymphopenias. Therefore, if a rapid drop in the absolute lymphocyte count to < 500/µl is observed at the start of treatment with dimethyl fumarate, an alternative to the drug should be sought – and given the multitude of alternatives in this segment of MS therapeutics, this is not a particular problem.
By the way, if the lymphocytes were hardly changed at the start of therapy (which is more often the case), the checks can be carried out less frequently after the first year. Nevertheless, I also recommend to those who have been taking dimethyl fumarate for a long time and may not have monitored as strictly at the beginning, to make sure that their absolute lymphocyte counts do not consistently fall below the threshold of 500/µl. If this is the case, it is better to look for alternative immunotherapy.
Lymphocyte values can fluctuate greatly. Even banal viral infections (e.g., an infection of the upper respiratory tract) can lead to temporary lymphopenia. Therefore, it is important not to panic immediately when an abnormal measurement is detected, but to first check whether it is actually a “long-lasting” problem.
In summary: Intensive monitoring of lymphocytes – especially in the first year of therapy – is useful under therapy with dimethyl fumarate (Tecfidera). Long-lasting lymphopenias are considered a risk factor for opportunistic infections. An absolute threshold value is repeated lymphocyte counts below 500/µl – but also repeatedly falling below 800/µl should lead to increased vigilance. In cases with long-lasting severe lymphopenias, an alternative to dimethyl fumarate (Tecfidera) should be discussed, although hasty reactions are not necessary.
