Shifting from treatment with Gilenya (fingolimod) to Lemtrada (alemtuzumab), and doing a short washout period between the two therapies, does not seem to increase the risk of disease reactivation in patients with multiple sclerosis (MS), an Italian study shows.
Lemtrada, marketed by Sanofi Genzyme, dramatically reduced MS inflammation, including the number of relapses and new brain lesions, compared to prior treatment with Gilenya (marketed by Novartis), according to the researchers.
The findings were presented on Oct. 11 at the 34th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Berlin, Germany, by Jessica Frau, MD, a neurologist at the Multiple Sclerosis Centre, University of Cagliari in Italy, in a presentation titled, “Shift from fingolimod to alemtuzumab: what happens next?”
Earlier studies reported a higher reactivation of MS in patients who start treatment with Lemtrada after they have been on Gilenya, especially if a short washout (a period without any of the treatments) was done between both.
Now, a team of scientists from several centers in Italy, led by researchers at the University of Cagliari, conducted a study to understand whether this treatment shift is really associated with an increased risk of MS reactivation, or if such a possible reactivation is to be expected when a treatment is changed due to ineffectiveness.
A total of 77 patients with relapsing MS were analyzed. They were changing therapies from Gilenya to Lemtrada due to treatment inefficacy. The patients were recruited from 11 Italian MS centers; had a mean age of 36.2; 79.2% were females; and they had a mean disease duration of 12.3 years.
The mean washout period between both treatments was 1.8 months. More than half of the patients, 49 out of 77, received more than one course of Lemtrada.
Before starting on Lemtrada, most patients (54.7%) had a normal lymphocyte count in the blood (more than 1,000 cells per microliter of blood), while the remaining had lower than normal counts.
Lymphocytes are a type of white blood cell that are crucial for fighting off infections, but that in many diseases, like MS, may start to mistakenly attack the body’s own tissues.
Both Gilenya and Lemtrada act by targeting lymphocytes, but while Gilenya works by inhibiting their infiltration into the central nervous system (the brain and spinal cord), Lemtrada reduces the amount of these cells (and other immune cells in circulation).
Results revealed that the annualized relapse rate (the average of relapses per year) in patients while receiving Gilenya was 0.60. It rose during the washout period to 1.33, then dropped to 0.20 after the start of treatment with Lemtrada.
After the shift in treatment, 11 patients had one or more relapses. The median time to first relapse during the washout period was 28 days, and much longer after the initiation of Lemtrada: a median of 315 days.
In the last MRI findings while patients were still taking Gilenya, new brain lesions in general (T2-weighted MRI) and new active lesions in particular (gadolinium-enhanced MRI) appeared in most patients — in 69.2% and 58.6% of the MS patients, respectively.
Comparatively, the first MRI scans after patients started receiving Lemtrada showed the emergence of new lesions in fewer patients — 10.4% (T2-weighted MRI) and 2.2% (gadolinium-enhanced MRI) of the patients.
No drop-outs from Lemtrada treatment were reported over the study period.
According to Frau, there was “no evidence of high disease activity in the first year of Lemtrada [treatment], when administered after Gilenya.”
“Alemtuzumab [Lemtrada] was able to dramatically reduce MS inflammation as compared to the previous fingolimod [Gilenya] treatment and the washout period,” Frau added.
This was true even if a short washout period was done and patients had a normal lymphocyte count when starting on Lemtrada, the researchers noted.
Therefore, “a rapid initiation of Lemtrada after Gilenya does not seem to be a risk factor for MS reactivation,” Frau wrote.
According to the researcher, the “optimal time [to switch therapies] could be maybe one month, when lymphocyte count is not low.”