NATIONAL HARBOR, Md. -- Patients on dimethyl fumarate (Tecfidera) may be at greater risk of lymphopenia if they are overweight, over age 40, white, and had low lymphocytes to start with, researchers reported here.
In a retrospective study of 196 patients, high vitamin D levels also appeared to be associated with a greater risk of lymphopenia, which is known to be a risk factor for progressive multifocal leukoencephalopathy (PML) with the drug, according to , of Beth Israel Deaconess Medical Center in Boston, and colleagues.
They reported their findings at the here.
"We can use this as a tool to monitor patients on Tecfidera," Sierra Morales told ľֱ. "If you have patients who are overweight or older than 40, you should watch their lymphocyte count. And if their baseline lymphocyte count is low, you should check it more frequently."
Several cases of PML have been reported with dimethyl fumarate, and patients on the drug who develop lymphopenia are said to be at greater risk for developing PML. So researchers have also been trying to determine which patients on the drug may be at greater risk of developing low lymphocyte count to begin with.
For their study, Sierra Morales and colleagues examined several factors that could be related to the development of lymphopenia, including age, prior natalizumab (Tysabri) exposure, low baseline absolute lymphocyte count (ALC), concomitant exposure to carbamazepine, smoking, steroids, opiates, and vitamin D levels.
They conducted a retrospective analysis of 196 MS patients treated with dimethyl fumarate at their center since 2013.
Patients were on the drug for a median of 17 months, and 21% developed grade 2 to 3 lymphopenia (8% developed grade 3 lymphopenia).
In Kaplan-Meier analyses, they found that low baseline ALC (P=0.008), BMI of 25 to 30 (P=0.008), and white race (P=0.037) were significantly associated with risk of grade 2 to 3 lymphopenia.
They also saw a trend for high average vitamin D levels and risk of lymphopenia.
Using Fisher's exact test, they found that high vitamin D levels (P=0.02), being older than 40 (P=0.03), and white race (P=0.01) were significantly associated with developing grade 2 to 3 lymphopenia.
Sierra Morales said that if lymphopenia occurs, the patient's vitamin D dose – multiple sclerosis patients take vitamin D because it is thought to have some relationship to the disease -- may need to be reduced to prevent further reductions in lymphocytes.
"We should check vitamin D level, and for those with supratherapeutic doses, maybe we can modify or optimize vitamin D supplementation to avoid worse lymphopenia," he said.
Gender, prior exposure to natalizumab, steroids, and carbamazepine were not associated with a risk of lymphopenia, they found. These results differ from previous studies that have shown natalizumab affects lymphopenia related to dimethyl fumarate, Sierra Morales said.
The researchers also found that dimethyl fumarate reduced CD8 cells more than CD4 cells (67% versus 39%, P<0.0007) and the CD4/CD8 ratio rose from 2.3 to 2.99 in those with lymphopenia (P<0.0009).
, of Massachusetts General Hospital in Boston, who was not involved in the study, said the findings "generally fit with what we thought about potential risk factors" for lymphopenia and PML.
"It will require more granularity for identifying who is at risk for PML, including additional screening panels for immune markers," Chitnis told ľֱ.
Disclosures
Co-authors disclosed financial relationships with Biogen, Genentech, Genzyme, Roche, and Teva.
Primary Source
Consortium of Multiple Sclerosis Centers Meeting
Sierra Morales F, et al "Risk factors for lymphopenia in patients with relapsing-remitting multiple sclerosis treated with dimethyl fumarate" CMSC 2016; Abstract DX32.