Induction therapies: more science is needed

Is the time right to compare HSCT to alemtuzumab? #MSBlog #MSResearch

My resistance to HSCT as a legitimate treatment for MS is gradually dissipating as I read and understand more about the procedure and its immunological effects. #MSBlog #MSResearch

"My post below from yesterday has generated a lot of discussion. The immunological observation that alemtuzumab leaves the rebooted immune system in a mess and HSCT doesn't is not a trivial one. It means that in terms of long-term safety HSCT may in fact be safer than alemtuzumab despite a higher early risk associated with the procedure. The only way we are going to sort this out is by doing a head-2-head study. In addition the study should be large enough and done well enough to get HSCT licensed as a treatment for MS. Without a license the payers won't pay for the procedure and neurologists would be forced to continue prescribing licensed therapies. It is clear that as a community you want the option of having a HSCT. If that is the case you need to start a lobby, or petition, to get the MS Society, NHS, NIHR, MRC, Wellcome Trust, etc. to take notice and fund a trial. If you want us to help lead the lobby we would be willing to do so. My resistance to HSCT as a legitimate treatment for MS is gradually dissipating a as I read and understand more about the procedure and its immunological effects."

"Please note I have reskinned to blog and we will stop using italics for personal opinions. One of our blog readers finds italics too difficult to read and found the blog too wide for small screens. I hope the narrower format and clearer text with better contrast makes it easier to read."

Yesterday's Post:

"I had a very interesting discussion this week with immunologists and MSologists about induction therapies. My definition of an induction therapy is any therapy that is given intermittently as a short course and works by depleting a subset, or subsets, of cell(s) and results in long-term remission of MS disease activity. In comparison to maintenance therapies, retreatment with an induction therapy is only necessary if MS disease activity reemerges. Current examples of induction therapies are alemtuzumab, cladribine, HSCT (hematopoietic stem cell therapy) or bone marrow transplantation (BMT) and possibly the anti-CD20s (rituximab, ocrelizumab and ofatumumab)."

"The most interesting aspect of our discussion was the discussion about what happens to the immune system when it reconstitutes itself. I haven't quite appreciated that with HSCT, or BMT , may be a better rebooter in that it results in a much healthier immune system post-induction; i.e. the reconstituted immune system post-HSCT may be closer to normal than the immune system post-alemtuzumab and the other therapies. This insight is in fact blindingly obvious; MSers are at very high risk of developing secondary autoimmunity post-alemtuzumab compared to post-HSCT. If HSCT became widely available as a treatment for MS this observation may make it more appealing than alemtuzumab. The other factor is efficacy; based on the open-label studies of HSCT, the reported NEDA rates seem to be higher than those achieved with alemtuzumab treatment, which implies that HSCT is likely to be more effective than alemtuzumab. I was also surprised to find out that in the UK HSCT will probably turn out to be cheaper than treating someone with alemtuzumab. All these factors (healthier post-induction immune system, greater efficacy and more cost-effective, make it essential that we do a trial comparing alemtuzumab to HSCT. May be we should take the ZEUS trial forward. What do you think?"

CoI: multiple

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