"In response to a discussion yesterday around the open-label alemtuzumab data from Cambridge I am re-posting the 5-year extension data from the phase 2 Alemtuzumab trial. As you can see MSers treated with Alemtuzumab do a lot better than those treated with interferon over 5 years. As always this comes with a price, namely the risk of secondary autoimmunity."
"A delegate at the Top Seminars meeting in Sorrento confronted me with the argument that the FDA used when they turned down Alemtuzumab in the US, that there is no evidence alemtuzumab is better than Rebif in drug-naive MSers. You may recall that there was not statistically significant difference between those with sustained progression on the CARE-MS 1 trial. I said that is fine if you are only prepared to look at the tip of the iceberg and even then alemtuzumab was superior to Rebif in relapse reduction. However, when you dive under the surface and look at end-organ damage you will see that the rate of brain volume loss in year 2 was 0.25% on alemtuzumab and 0.5% on Rebif (slide 16 below). Please remember that normal people lose between 0.1% and 0.4% of their brain volume per year after the age of 35."
"Which drug, alemtuzumab or interferon-beta, is preventing end-organ damage? Which drug will keep your brain healthy for old age? People always see what they want to see in the data."
"The natural conclusion of moving the therapeutic goal posts in MS to preventing end-organ damage is that you need to get on to the most effective DMTs as soon as possible in the course of the disease. I have tried to illustrate this in slides 50 to 56 below; only early highly-effective treatments can protect your brain sufficiently to give you a chance in old age."
Coles AJ, et al. Alemtuzumab more effective than interferon β-1a at 5-year follow-up of CAMMS223 Clinical Trial. Neurology. 2012 Apr 3;78(14):1069-78.
OBJECTIVE: To report the long-term safety and efficacy results from CAMMS223 comparing alemtuzumab with interferon β-1a in early, active relapsing-remitting multiple sclerosis (RRMS). What are the long-term effects of alemtuzumab treatment, received 36 to 48 months previously, on relapse and disability in early, active RRMS? This study provides evidence of the effectiveness of alemtuzumab in reducing the relapse rate and accumulation of disability compared with interferon β-1a (IFNβ-1a) through extended follow-up (up to 60 months from baseline).
METHODS: Of 334 MSers originally randomized, 198 participated in the extension phase (151 [68%] alemtuzumab and 47 [42%] IFNβ-1a). Disability, relapses, and safety were assessed as in the original study period. Efficacy outcomes were analyzed from baseline of the original trial period to 60 months. Safety data extended beyond 60 months.
RESULTS: Over 5 years, alemtuzumab lowered the risk of sustained accumulation of disability by 72% and the rate of relapse by 69% compared with IFNβ-1a (both p < 0.0001). The annualized relapse rate from baseline to month 60 was 0.11 for alemtuzumab and 0.35 for IFNβ-1a. Complete safety follow-up reflected 988 and 376 person-years for alemtuzumab and IFNβ-1a patients, respectively. Serious infections were seen in 7% of alemtuzumab patients and 3% of IFNβ-1a patients, and thyroid disorders were seen in 30% of alemtuzumab patients vs 4% of IFNβ-1a patients. Immune thrombocytopenia (autoimmune attack of platelets) occurred in 3% of alemtuzumab patients and 0.9% of IFNβ-1a patients during the initial study period; no additional events were reported during the extension phase. One alemtuzumab-treated MSer developed Goodpasture disease 39 months after the second annual cycle of alemtuzumab.
CONCLUSIONS: Through extended follow-up, alemtuzumab remained significantly more efficacious than IFNβ-1a, with a safety profile consistent with previous reports.