An update of the long-term efficacy and safety data of alemtuzumab in patients with relapsing-remitting MS was presented at the 5th Annual Congress of the European Academy of Neurology (EAN) in Oslo, Norway last weekend.
Prof. Giancarlo Comi presented evidence of improved clinical and MRI outcomes in patients from the TOPAZ study, an open-label extension study for patients from the CARE-MS I trial1,2 who received alemtuzumab in comparison with subcutaneous interferon-beta 1a for two years. The dosing scheme for the treatment-naïve patients who had not previously received MS disease-modifying therapies was alemtuzumab 12 mg per day by intravenous (IV) infusion over five consecutive days at baseline, followed by alemtuzumab 12 mg per day by IV infusion over three consecutive days at 12 months.
Robust long-term follow-up data on alemtuzumab
In the open-label extension study TOPAZ3, the efficacy of alemtuzumab in treating clinical MRI lesions and brain volume loss was maintained over 8 years in patients with active RRMS who were treatment-naïve prior to alemtuzumab administration. 77% (290/376) of patients completed the last year of the TOPAZ extension study that corresponded to a total follow-up time of 8 years, and 56% of patients received neither alemtuzumab nor any other disease-modifying therapy. Additional as-needed alemtuzumab doses could be given at the discretion of the treating physician (given as 12 mg doses on three consecutive days in intervals of at least 12 months).
At the end of the 8-year follow-up, nearly 60% of patients achieved no evidence of disease activity (NEDA). This included 67% of patients without MRI disease activity and 84–89% of patients who remained relapse-free annually. Most importantly, the cumulative rate of patients with complete absence of disease activity in the extension study (Years 3 to 8) according to the NEDA criteria was 25%, and freedom from MRI disease activity at the end of the eight-year follow-up period was sustained at 38%.
Maintained impact on disability status and brain volume loss
A majority of patients also showed a stabilisation of disability progression – 56% of the enrolled participants had stable EDSS scores and 22% showed improvements in their EDSS. Within the last year of the extension study (Year 8), 71% of patients did not experience any worsening of their 6-month confirmed disability and 41% of patients even exhibited improvements. The levels of brain volume loss (BVL) were also positively affected by alemtuzumab treatment, with cumulative BVL being -1.83% from the core study through Year 8. This corresponded to an annual BVL of less than 0.22% – a value that approaches the percentage seen in healthy populations.
The safety findings were consistent with previous analyses and the overall incidence of adverse events (AEs). Serious individual cardiovascular and autoimmune AEs have occurred with alemtuzumab treatment in the post-marketing setting, with autoimmune AEs peaking during Year 3 following alemtuzumab initiation, only to then decline to prior levels.
- Cohen J, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet 2012;380:1819-28.
- Havrdova E, et al. Alemtuzumab CARE-MS I 5-year follow-up. Durable efficacy in the absence of continuous MS therapy. Neurology 2017; 89(11): 1107–16.