Multiple Sclerosis Drug Switching May Trigger Disease Progression

A new study finds that switching multiple sclerosis (MS) treatments may negatively impact disease progression.

Specifically, certain patients with MS who switched from treatment with Gilenya (fingolimod) to Lemtrada (alemtuzumab) experienced significant disease activity, according to a recent study published by Neurology: Neuroimmunology & Neuroinflammation.

Current MS treatments target immune cell trafficking, lymphocyte function, and lymphodepletion. With an increasing number of available treatments, understanding the long-term consequences of sequential drug use, and the order used is still unclear. However, these factors must be determined to ensure that patients are receiving the optimal treatment.

Gilenya is a sphingosine 1-phosphate (S1P1) receptor modulator that decreases the number of lymphocytes that enter the central nervous system. Lemtrada is an antibody that targets T cells and B cells, which attack the myelin sheath in patients with MS.

Researchers at 6 different centers throughout Europe found that patients who achieved disease control with Gilenya experienced adverse events after switching treatment to Lemtrada.

“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.

In total, the 6 centers treated 174 patients with Lemtrada, with 36 who were previously treated with Gilenya. The clinicians found that 9 of the patients experienced severe, unexpected disease activity after switching treatment.

Lemtrada has a confirmed efficacy profile of reducing relapse frequency up to 74%, compared with competing drugs. However, all patients who newly-switched treatments and who did not respond to Lemtrada experienced new disease activity.

While there was potential bias in selecting the group of patients, the study authors found that administering Lemtrada to patients with MS after Gilenya may reduce efficacy, according to the study.

The unexpected disease activity could result in long-term sequestration of auto-reactive immune cells in the lymph nodes after Gilenya cessation, the authors wrote. The sequestrations may allow the cells to essentially hide from treatment with Lemtrada.

After the drug’s effect has passed, the immune cells could emerge and reactivate MS symptoms, the authors hypothesized.

Other factors that could impact MS disease activity include S1P1 overexpression, lymphocyte retreat, and the modification of immune cells.

Additional preclinical and clinical studies are needed to further confirm these findings. However, physicians should consider individual treatments options for each patients and the potential effects of switching therapies, especially from Gilenya to Lemtrada.

“In particular, careful consideration needs to be given to mode of action of individual therapies and sequential treatment effects,” the study concluded.