ClinicSpeak: sequencing DMTs, alemtuzumab after mitoxantrone

Time is brain. #ClinicSpeak #MSBlog #MSResearch

"The new buzz word in MS is sequencing of therapies. The study below is reassuring in that MSers with very active disease despite being treated with mitoxantrone responded to alemtuzumab. I have personally treated one such patient in the UK and he has done very well, in that he is NEDA. Unfortunately, prior to receiving mitoxantrone, and subsequently alemtuzumab, he had accumulated already accumulated severe disability (EDSS 7.0) and a lot of cognitive impairment. He has also subsequently become hypothyroid. This case and the study below reinforces the message that if you want to maximise the treatment benefits of alemtuzumab you need to use it as early as possible in the course of the disease."

"To maximise the benefits of highly effective treatments you need to use them early before you have acquire irreversible damage or lost brain and hence reserve capacity. Time is brain!"


Epub: Le Page et al. Alemtuzumab as rescue therapy in a cohort of 16 aggressive multiple sclerosis patients previously treated by Mitoxantrone: an observational study. J Neurol. 2015 Feb 21. 

Objective: Our study aimed to describe safety and neurological impact of alemtuzumab as last-line rescue therapy in MSers with aggressive MS, previously treated by Mitoxantrone (MITOX). 


Methods: Between June 2004 and October 2013, 13 MSers received alemtuzumab at 20 mg/day and 3 at 12 mg/day for 5 days. EDSS, relapses, secondary progression were prospectively assessed 12 and 6 months before treatment, at baseline and every 3 months. 

Results: Mean follow-up was 6.2 years [1-10]. Mean age at alemtuzumab start was 40 years [26-49] for 8 Secondary Progressive (SP) and 30 years [26-35] for 8 Relapsing-Remitting (RR) MSers. MS duration was 13.7 (±3) and 8.3 (±4) years, respectively. During the 12 months before alemtuzumab, annual relapse rate was 0.75 and 3.14, respectively and the 16 MSers accumulated 2-30 new gadolinium enhancing lesions. 4 MSers (suboptimal responders) received alemtuzumab during MITOX and 12 MSers 1-7.8 years after MITOX. Out of 8 SPMS, 2 were disease free up to last visit (4.7 and 8 years), 5 improved or stabilized but only transiently and 1 worsened. Out of 8 RRMS, 1 remained stable up to last visit (8.7 years) despite 1 relapse and active MRI at 18 months and 7 improved (1-4 point EDSS): 4 remained disease free up to last visit (12, 24, 38 months and 7 years), 2 were successfully retreated at 25 and 33 months and 1 worsened progressively 24 months after alemtuzumab. 2 MSers developed Grave's disease and 1 hypothyroidism. 

Conclusion: Alemtuzumab controls aggressive RRMS despite previous use of MITOX.

CoI: multiple

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