FDA-Approved Medications: New Data
- Intravenous infusion over four hours for two treatment courses:
First course: 12 mg/day on five consecutive days.
Second course: 12 mg/day on three consecutive days 12 months after first treatment course.
- Approved in 2012 for RMS
Lemtrada® (alemtuzumab) is a monoclonal antibody. Its exact mechanism of action is unknown, but is believed to involve binding to a cell surface antigen found on key immune-system cells, including T and B lymphocytes, leading to the depletion of these cells and other effects on the inflammatory process. Because Lemtrada can cause serious autoimmune conditions and infusion reactions, and can increase the risk for some cancers, its use typically is reserved for patients who have had an inadequate response to two or more other MS disease-modifying therapies.
Researchers assessed the long-term efficacy and safety of Lemtrada in 349 patients with active RMS.24 The data they reported covered an initial two-year core study, called CARE-1, and a three-year extension study. During the follow-up period, patients were eligible to be re-treated with Lemtrada if they had a relapse or MRI activity.
At the end of Year 5, 88 percent of the participants had not had a relapse, 87 percent did not have a brain or spinal cord lesion seen on gadolinium-enhanced MRI, and 85 percent were free of clinical disease activity. Sixty percent of participants saw their EDSS score remain stable, while 22 percent saw their EDSS score improve and 18 percent had their score worsen.
Adverse events occurred more frequently in the two years of the core study than in the following three years of the extension study, and 97 percent of the adverse events reported in Years 3-5 were mild to moderate in severity. However, one patient died of sepsis in Year 3, in what was judged to be a treatment-related adverse event. Thyroid issues were the most common autoimmune adverse events reported during the extension period; they peaked in Year 3 at a 15-percent incidence.
During the extension period, 67.3 percent of the participants received neither Lemtrada re-treatment or treatment with any other disease-modifying therapy (DMT), leading the investigators to conclude that Lemtrada had enduring efficacy in the three years following conclusion of its two-course treatment.
The long-term effects of Lemtrada also were the focus of several presentations at the ECTRIMS-ACTRIMS Meeting in 2017. Investigators drew on data from another long-term follow-up study (TOPAZ; NCT02255656) of people with RMS who had participated in earlier Lemtrada trials. Researchers reported that:
- People with RMS who switched from interferon beta-1a to Lemtrada saw improved clinical outcomes, decreased MRI disease activity, slowed brain volume loss, and durable efficacy in the five years after being treated with Lemtrada.25, 26, 27
- Through seven years of follow-up from the time of initial Lemtrada treatment, 74 percent of participants were free from six-month confirmed disability worsening, and the annualized relapse rate (ARR) at Year 7 was 0.13.28 Furthermore, 68 percent of these individuals were free of MRI disease activity at Year 7, and Lemtrada consistently slowed brain-volume loss throughout the study period.29
Related research presented at the 2017 ECTRIMS-ACTRIMS Meeting reported that over a median follow-up period of 5.8 years, 18 percent of Lemtrada-treated patients converted from relapsing-remitting MS to secondary-progressive MS. The investigators termed this a low rate of conversion based on criteria they specified at the outset of their study.30
Taken as a whole, these findings provide reassurance that Lemtrada has a long-term favorable effect on the course of RMS as measured by a number of different standards. This re-assurance is important for clinicians and patients alike, given the well-documented safety concerns involved with Lemtrada. These data will aid in decision-making when the patient and physician need to consider next steps following an inadequate response to another MS therapy.