Lemtrada controlled RRMS disease activity more than a decade
Final results of the open-label TOPAZ clinical trial include low relapse rates
Over more than a decade of treatment with Lemtrada (alemtuzumab), relapse rates were low and about half of people with relapsing-remitting multiple sclerosis (RRMS) remained free of confirmed disability worsening, according to final results from the open-label TOPAZ clinical trial.
“To our knowledge, this report represents the longest prospective follow-up of people with RRMS who received [Lemtrada] and is the most comprehensive description of [Lemtrada]’s benefit-risk profile for RRMS,” the researchers wrote.
“Over 11 years, [Lemtrada]’s therapeutic effects on [relapse rates], disability, and MRI outcomes, including annual brain volume loss, were maintained and most participants either did not require additional courses or needed just one additional course,” they added.
The study, “Safety and efficacy with alemtuzumab over 13 years in relapsing-remitting multiple sclerosis: final results from the open-label TOPAZ study,” was published in Therapeutic Advances in Neurological Disorders. The work was funded by Sanofi, which markets Lemtrada.
Lemtrada is an approved treatment for RRMS that works by destroying B-cells and T-cells, which are immune cells that drive inflammation in MS. Because this powerful immune-suppressing therapy can cause serious side effects, such as infections and autoimmune disorders, it usually is prescribed only to people with RRMS who have failed to respond to other treatments.
Lemtrada is administered via infusion into the bloodstream. Under the approved dosing schedule, patients receive five infusions over five consecutive days, then one year later they get another three infusions over three consecutive days. In subsequent years more rounds of infusions are given as needed.
Approvals of Lemtrada were based on data from two Phase 3 studies: CARE-MS 1 (NCT00530348), which enrolled people with RRMS who never had been treated before, and CARE-MS 2 (NCT00548405), which included patients who had experienced a relapse or flare while on another therapy.
Both CARE-MS trials tested Lemtrada against the older approved therapy Rebif (interferon beta-1a) for two years. Results showed Lemtrada outperformed Rebif at reducing relapse rates and lowering disease activity on MRI scans in both studies. In the CARE-MS 2 study of previously-treated patients, those given Lemtrada also had less disability progression.
Patients who completed either of these studies had the option to enroll in an extension study (NCT00930553), where those previously given Rebif were switched to Lemtrada, and those who received Lemtrada in the original studies were given additional infusions of Lemtrada as needed.
After completing the extension trial, participants could enter another study called TOPAZ (NCT02255656), where they continued receiving Lemtrada as needed.
Patients followed up to 13 years across all studies
Now, an international team of researchers reported final results from the TOPAZ study, with 11 years of follow-up across all the studies. A few patients were followed longer, up to 13 years total.
The researchers particularly focused on findings from patients who originally had been in CARE-MS 2, because in real-world practice Lemtrada usually is given only to patients who’ve had disease activity while on other treatments.
Among patients who completed the TOPAZ study, there were 207 who had been given Lemtrada and 78 who had received Rebif in CARE-MS 2. There also were 257 patients given Lemtrada and 109 given Rebif in CARE-MS 1.
For patients who were on Lemtrada the whole time, roughly half — 43.5% in CARE-MS 2 and 54.2% in CARE-MS 1 — required only the initial two rounds of infusions. Most patients who received additional infusions received only one additional round of infusion (three rounds total).
Over the course of follow-up, the average relapse rates lower than 0.2 per year — or less than one relapse every five years, on average — for both patients who had been always on Lemtrada and those who had switched from Rebif. The relapse rates tended to be highest in the first years after starting on Lemtrada, getting lower over more years of follow-up.
EDSS used to track disability levels
Disability levels were tracked in the trial using the Expanded Disability Status Scale (EDSS). For previously-treated patients given Lemtrada in CARE-MS 2, nearly half (45.9%) had stable EDSS scores over more than a decade of follow-up, and another 20.5% of patients experienced a decrease of at least one point in EDSS scores, suggesting less-severe disability. Only about a third of patients in this group experienced a notable worsening in disability.
These rates were similar for patients originally given Rebif in CARE-MS 2 who switched to Lemtrada in the extension study. However, the researchers noted that more patients who were always on Lemtrada were free from confirmed disability progression — a worsening in disability levels lasting at least six months — than those who first started on Rebif (58% vs. 51%).
MRI data also showed that, from years 3 to 11, most patients did not have any newly inflamed lesions or lesions with definitive nerve damage on MRI scans, and brain atrophy (shrinkage) was generally minimal for patients on Lemtrada.
“Efficacy findings suggest that the clinical benefit of [Lemtrada] is maintained for at least 11 years after the initial course in most people with RRMS,” the researchers concluded.
Lemtrada safety data consistent with previous clinical trials
Safety data from the long-term follow-up study were generally consistent with data from the original clinical trials. More than 90% of patients given Lemtrada experienced infusion-related reactions, and nearly half experienced side effects involving the thyroid. Serious side effects were reported for about four of every 10 patients given long-term Lemtrada.
The researchers noted that side effects of all kinds were most common in the first years of Lemtrada treatment, and then were notably less common over long-term follow-up. There weren’t notable differences in side effect profiles for patients who required additional rounds of Lemtrada infusions, though side effects were a bit more common for these patients.
“Safety risks associated with [Lemtrada] treatment declined over time … and were similar for participants who did or did not receive additional courses,” the researchers wrote.
Overall, the scientists said this study “supports a positive, long-term benefit-risk balance of [Lemtrada] for people with RRMS who had an inadequate response to other [treatments] or were previously treatment-naïve.”
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