BACKGROUND:Alemtuzumab has recently been approved for treatment of relapsing MS, but concerns remain about its use since long-term studies of adverse events remain limited. Furthermore, a clear understanding of its application and durability of effect in clinical practice has yet to evolve.
OBJECTIVES:To investigate long-term efficacy and safety outcomes in a multicentre cohort of patients treated with alemtuzumab.
METHODS:Patients treated from 2000 and followed-up at three regional centres were identified. Baseline and prospective data were obtained and validated by clinical record review.
RESULTS:One hundred patients were identified with a mean follow-up of 6.1 years (range 1-13). Forty patients were retreated with at least one further treatment cycle. Annualized relapse rates fell from 2.1 to 0.2 (p<0.0001) post-treatment and were sustained for up to eight years of follow-up. Mean change in EDSS score was +0.14. Forty-seven patients developed secondary autoimmunity.
CONCLUSION: Observed reduction in relapse rates reflected those reported in clinical trials, but we were unable to corroborate previous observations of disability reversal. 40% of patients required additional treatment cycles. Autoimmune adverse events were common, occurring at a higher rate than previously reported, but were largely predictable, and could be managed effectively within a rigorous monitoring regime.
So this is the real life data from the west of England and Wales and shows that after mean of 6 years 60% of people had not needed treatment for the past 5 years and relapses had substantial dropped.
The majority of patients (53%) underwent or were planned to complete the standard two cycles of treatment. 28% patients received three treatments, 11% four treatments and one patient five treatments. Seven patients received one treatment cycle only. Between two and five years, 27% of patients had been retreated, increasing to 51% and 58% at five to ten years and greater than ten years follow-up, respectively. A small number of patients were unresponsive to treatment and continued to experience frequent clinical relapses: four patients had 10 post treatment relapses and had a post treatment ARR of >1.
The EDSS level in this group did not get better in comparision to the people in Cambridge. This may because people were in active disease when they started Alemtuzumab and showed recover. However the lesson here if you are going down this route do not expect what has been lost to be recovered and what you are trying to do is stop the condition getting worse. So when should you start to save brain, the sooner the better. Mean baseline EDSS was 4.0. Mean change in EDSS from treatment baseline was +0.14.
The level of autoimmunity was much higher than the trials and came in at about 50% and this is similar to the longer term follow up. So this is an Achilles heel. If anti-CD20 comes along with similar efficacy and no autoimmunity it maybe bye bye CAMPATH so this aspect needs to get sorted ASAP.
Ten patients i.e 10% developed pre-malignant or malignant conditions during the period of follow-up.
Thirteen pregnancies were recorded in twelve women (18%). Two pregnancies resulted in miscarriage and one was terminated.
The result you want to know is this how many people became secondary progressive and the answer was twelve patients (12%) were considered to have developed secondary progressive disease a mean of 3.8 years after initial treatment. Were these the people who did not respond