Switching From Gilenya to Lemtrada Seen to Trigger Disease Activity in Some MS Patients

Switching treatments from Gilenya (fingolimod) to Lemtrada (alemtuzumab) triggers significant and unexpected disease activity in some patients with multiple sclerosis (MS), a study reported.

Clinicians at six centers across Europe noticed this phenomenon, independently and at the same time.

“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,” suggested the authors of the study, “An observational study of alemtuzumab following fingolimod for multiple sclerosis.” It was published in the scientific journal Neurology Neuroimmunology and Neuroinflammation.

The six centers — three in Britain, and the others in Denmark, Sweden and the Netherlands — have treated a combined 174 patients with Lemtrada. Of those, 36 had previously taken Gilenya; nine of them showed unexpected and significant disease activity following the switch to Lemtrada.

Although the researchers recognize the potential selection bias in this group of patients, they suggest that this result may mean that treating MS with Lemtrada after Gilenya could reduce therapeutic efficacy in some patients. 

They say this unexpected activity, despite Lemtrada’s established efficacy, may result from the prolonged sequestration of auto-reactive immune cells in the lymph nodes following Gilenya withdrawal. This sequestration would allow such cells to be concealed from the usual biological effect of Lemtrada of neutralizing them. Once the drug’s effect has passed, these cells could re-emerge from the lymph nodes and reactivate the disease.

Further animal studies and clinical trials are needed to confirm these findings, say the authors, adding that, meanwhile, physicians should carefully consider individual therapies and the effects of sequential treatments in MS when designing personalized treatment regimens.

Lemtrada is an antibody that targets certain cells of the immune system, called T- and B-cells, for destruction. These cells attack the myelin sheath covering nerve cells in MS. Previous clinical trials have shown that Lemtrada reduced relapse frequency in MS patients by up to 74 percent, and reduced annualized relapse rates from 2.1 to 0.2.