Alemtuzumab Shows Durable Efficacy for RRMS in TOPAZ Study
OCTOBER 27, 2017
Aaron Boster, MDTreatment with alemtuzumab (Lemtrada) demonstrated significant reductions in MRI lesions and durably slowed brain volume loss (BVL) in the absence of continuous treatment for patients with relapsing-remitting multiple sclerosis (RRMS), according to a 5-year follow-up analysis of presented at the 2017 MS Paris meeting.
The TOPAZ study examined alemtuzumab in patients with RRMS who were treated with subcutaneous IFNB-1a for 2 years in the CARE-MS I or II trials. Despite most patients having not received additional therapy after initial treatment with alemtuzumab, 67% remained free of MRI disease activity at 5 years. The annual brain parenchymal fraction (BPF) change was -0.13 and -0.08 at the 5-year assessment for those in the CARE-MSI and II studies, respectively.
“I’m very excited about long-term follow-up data,” study author Aaron Boster, MD, neuroimmunologist from OhioHealth Neurological, told MD Magazine. “When you do a 2-year clinical trial, it’s a very short [time]. MS is measured by decades. The person is going to live with the condition for 30 to 40 years. As such, a 2-year clinical investigation may be fully inadequate to really have a meaningful conversation in the real-world about what to expect.”
In the CARE-MS I trial, after 2 years in the trial, 139 IFNB-1a-treated patients went on to receive alemtuzumab. Overall, 122 entered the TOPAZ study with 118 completing year 5. In the CARE-MS II study, 143 patients treated with IFNB-1a initiated alemtuzumab in the extension study, of which 123 entered the TOPAZ study with 119 completing the analysis.
In the extension stage for each study, alemtuzumab was given at 12 mg/day for 5 consecutive days followed by 3 consecutive days 12 months later. Patients could receive treatment with alemtuzumab or another disease-modifying therapy (DMT) as needed for relapse or MRI activity. Overall, 71% and 61% of patients only required the 2 initial courses of alemtuzumab in CARE-MS I and II, respectively.
In the core study for CARE-MS I and II, 59% and 47% of patients were free of MRI disease activity with IFNB-1a. MRI disease activity was defined as a new Gd-enhancing T1 lesion or new/enlarging T2 hyperintense lesion. Following initiation of alemtuzumab in the extension study, 82% and 81% of patients were free of MRI activity, in CARE-MS I and II, respectively. By year 5, 67% of patients were free of MRI disease activity in both studies.
In the core study, the annualized relapse rates (ARR) with IFNB-1a were 0.39 and 0.52 for CARE-MS I and II, respectively. Following treatment with alemtuzumab, these rates declined to 0.11 in CARE-MS I and 0.15 for CARE-MS II. In the TOPAZ results, the ARR was 0.09 and 0.18 for CARE-MS I and II, respectively.
“[This study and others] looked at alemtuzumab and the years long follow-up data, and it’s amazing,” Boster said. “What we’re seeing is that going out over [years], even though half the patients never got retreated, there’s a durable effect. We’re seeing a maintenance of a very, very low annualized relapse rate."
For BVL, in the core study, the median annual BPFs were -0.50 and -0.33 in years 2 of IFNB-1a treatment for CARE-MS I and II, respectively. However, with alemtuzumab, the median annual changes in BPF dropped to -0.07 and +0.02 in year 1 of the extension study, for CARE-MS I and II, respectively, and were -0.13 and -0.08 for the TOPAZ results.
For the TOPAZ results, expanded disability status scale (EDSS) score did not significantly worsen for 75% and 74% of those treated with alemtuzumab in the CARE-MS I and II groups, respectively. In fact, 28% of patients in CARE-MS I and 23% of those in CARE-MS II experienced an EDSS improvement of ≥1 point with alemtuzumab.
"Confirmed disability progression diminishes and stays remarkably low. MRI measures, including atrophy and inflammatory measures, remain amazingly low despite retreatment," said Boster. "Most importantly, the side effect profiles aren’t changing. Having that information at hand, I can now go back to Columbus, Ohio, and treat people and share with them our expectations, now going out 7 years. It’s really meaningful.”