麻豆传媒

INDIANAPOLIS -- Real-world experience with lymphopenia in multiple sclerosis patients receiving dimethyl fumarate (Tecfidera) is generally similar to that seen in clinical trials, but researchers here said they would recommend checking lymphocyte counts earlier than currently recommended.

In a study of patients at an MS clinic in Rochester, N.Y., 45% of those treated with dimethyl fumarate developed lymphopenia, according to , of the University of Rochester. But the time it took for lymphocyte count to drop ranged from 2 to 22 months.

"We had been doing monitoring every 6 months [the label-recommended interval], but we may start checking 3 months after initiation of therapy," Robb told 麻豆传媒.

In a second study, of patients at an MS clinic in Calgary in Canada, dimethyl fumarate patients had a mean reduction in lymphocyte count of 34% at 1 year, though it remained within normal limits, according to , of the University of Calgary.

"We do more intensive testing of once a month after starting therapy, but that seems excessive in the first 6 months of treatment," Almalik told 麻豆传媒. "Every 3 months seems to be more reasonable."

Both studies were reported at the here.

Lymphopenia has been a concern with dimethyl fumarate since it may indicate heightened risk for progressive multifocal leukoencephalopathy (PML). Last year, an MS patient enrolled in an extension study of the drug developed a fatal case of PML, as did a psoriasis patient who was taking a compounded version of the drug. Both cases were recently detailed in the New England Journal of Medicine.

Since the MS patient developed the disease only after a prolonged period of lymphopenia -- some 3.5 years -- researchers have been trying to clarify the role of lymphopenia in PML and better define utility of lymphocyte counts in predicting PML risk.

For their study, Robb and colleagues conducted a retrospective chart review of 159 patients seen at their facility. A total of 45% developed lymphopenia. Of these patients, 20% developed grade 1 lymphopenia, 21% developed grade 2 disease, and 4% developed grade 3.

Lymphocyte count nadir occurred at a mean of 10.5 months, Robb said, but it ranged from 2 to 21.7 months, indicating a need to monitor lymphocyte counts earlier, she said.

She noted that while the risk of opportunistic infections is likely due to more prolonged lymphopenia, the condition won't resolve while patients remain on treatment. Earlier detection gives physicians more time to make decisions and discuss the risks and benefits of continued treatment with patients, she said.

In the Canadian study, Almalik and colleagues assessed 170 MS patients treated at their clinic with dimethyl fumarate. They found that at 1 year, mean lymphocyte count fell by 34% from baseline -- although it remained within normal limits -- and the decline was significant from baseline at 3, 6, and 12 months (P<0.001).

A total of 11% of patients developed grade 2 lymphopenia, and 5.5% developed grade 3 disease.

For grade 2, the median time to first occurrence was 6.4 months, and only one patient decided to discontinue treatment because they were concerned about their abnormal lab results and had flushing as a side effect.

For grade 3, the median time to first occurrence was 6.3 months, and only one patient decided to stop therapy because they weren't feeling well, Almalik said.

He concluded that their data were consistent with the Canadian drug monograph for dimethyl fumarate, and that their more intensive strategy of monthly testing was overkill, particularly in the first 6 months of therapy.

Instead, the data supported testing every 3 months in the first year of treatment, he said, and patient adherence to this safety monitoring is typically good.

Both groups of researchers called for future studies of larger populations to better understand the development of lymphopenia in patients on dimethyl fumarate and evaluate its potential role in PML.

, of Mount Sinai Hospital in New York, who was not involved in the studies, said the lone case of PML in a patient on dimethyl fumarate is the one researchers can learn the most from.

"We need to watch for PML, and identify lymphopenia in order to minimize risk," Krieger said. "There's not a lot of experience with this, but generally if lymphopenia is sustained below 500, we won't keep a patient on Tecfidera."

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