Unexpected Disease Activity Observed From Multiple Sclerosis Drug Swap

A change from fingolimod to alemtuzumab caused significant disease activity in patients with MS.

Some patients with multiple sclerosis (MS) experienced significant and unexpected disease activity after switching from fingolimod (Gilenya) to alemtuzumab (Lemtrada), a new study published in Neurology Neuroimmunology & Neuroinflammation found.

The phenomenon was observed at 6 European neuroscience centers that treated 174 patients with alemtuzumab collectively, of whom 36 had previously taken fingolimod and 9 showed significant disease activity following the switch to alemtuzumab.

The median disease duration to alemtuzumab treatment was 94 months, and follow-up from time of the initial alemtuzumab cycle was 20 months.

After the first infusion cycle of alemtuzumab, 8 patients were identified by at least 1 clinical relapse and radiologic disease activity, and 1 by significant radiologic disease activity alone. All patients experienced a lack of response to alemtuzumab with significant disease activity.

“We hypothesize that this occurs as a result of prolonged lymph node sequestration of circulating lymphocytes following fingolimod withdrawal, which in turn limits the efficacy of alemtuzumab,” the authors wrote. “Other factors that may influence disease activity included S1P1 overexpression and subsequent lymphocyte egress contributing to accelerated repopulation and modification of the circulating immune repertoire by fingolimod altering the expected deletion pattern following alemtuzumab.”

Alemtuzumab is a humanized monoclonal antibody designed to target the cell surface protein CD52. Treatment results in a significant and rapid reduction in peripheral lymphocytes as a result of antibody-dependent cell-mediated cytotoxicity, complement-dependent cytolysis, and apoptosis.

Fingolimod is an oral disease-modifying treatment that causes internalization of S1P type 1 receptors, and inhibits lymphocyte trafficking from secondary lymphoid organs in the peripheral circulation.

The findings of the study could be a result of pathogenic lymphocytes that may continue to be released from the lymphoid system over a more prolonged period of time in some patients.

“We acknowledge the potential for ascertainment bias; however, these cases may illustrate an important cause of reduced efficacy of alemtuzumab in a vulnerable group of patients with MS most in need of disease control,” the authors wrote.

To further confirm the findings, animal studies and clinical trials are needed, the authors noted.

“In the meantime careful consideration should be given to mode of action of individual therapies and sequential treatment effects in MS when designing personalized treatment regimens,” the authors concluded.