Even patients without lymphocytopenia may be at risk of opportunistic infections while on dimethyl fumarate (DMF), researchers reported in .
The oral drug is FDA-approved under the name Tecfidera for treating multiple sclerosis; it has also been sold in Europe for many years under different names and in compounded formulations for treating psoriasis. DMF in both uses has been linked to cases of progressive multifocal leukoencephalopathy (PML), a life-threatening brain inflammation that results from reactivation of latent JC virus infection.
Lymphocytopenia is a known side effect of the drug and most of the PML cases have occurred in patients showing it. But increasingly it appears that it's not necessary for opportunistic infections to develop.
One of the NEJM letters described a 23-year-old male psoriasis patient in the Netherlands taking DMF for psoriasis (Fagron), who developed shingles 2 months after starting the drug -- without lymphocytopenia, according to , of Leiden University Medical Center in The Netherlands, and colleagues.
He'd had chickenpox during childhood, and testing confirmed varicella-zoster virus infection. He had IgM antibodies to the virus, but no IgG response, they noted. He had no other treatment, such as ultraviolet light therapy or topical glucocorticoids.
"This case suggests that patients treated with DMF may have increased risk of viral infection, even in the absence of lymphocytopenia," they wrote.
In another letter, , and Enes Hajdarbegovic, MD, of Erasmus Medical Center in the Netherlands, noted that DMF has been shown to reduce specific lymphocyte subpopulations even when total lymphocyte count is normal.
In one instance, a psoriasis patient on the drug developed a herpesvirus 8-related Kaposi's sarcoma with normal total lymphocyte counts but low levels of CD4+ and CD8+ cells.
"It may be important to assess cell counts of specific lymphocyte subsets during treatment with DMF," they wrote.
, and colleagues, who had reported a case of PML in a patient on DMF who didn't have severe lymphocytopenia in NEJM responded to the letters, agreeing that patients on the drug may be at risk of opportunistic infections even with normal total lymphocyte counts.
They cited a taking DMF for psoriasis (Fumaderm) who'd had only moderate (grade 2) lymphocytopenia.
A search of PubMed abstracts identified a total 10 cases of PML reported with various formulations of dimethyl fumarate in the past decade, mostly in psoriasis patients.
Nieuwkamp and colleagues said that safety monitoring of patients on DMF is "crucial" and that further studies on how to identify at-risk patients are "urgently needed."