A question about whether or not currently licensed DMTs are effective in African-Americans has arisen. Why?
Lack of evidence does not mean lack of efficacy.
If you are a non-Caucasian pwMS you will become disabled quicker than your Caucasian counterparts. The evidence that so-called ‘non-whites’, which includes African-Americans, Africans and Asian do worse than ‘whites’ is pretty well accepted. However, most of this data was derived from the pre-DMT and 1st-generation, or injectable (IFNbeta and GA), DMT eras. The question of whether or not the same now holds true in the post-Natalizumab era is unclear.
Jagannadha Avasarala suggests in an editorial below that we should question the assumption that licensed DMTs work in these populations because we don’t have the necessary data to support our assumptions. Why? Simply, because there are too few African-Americans, Africans and Asians in the pivotal phase 3 trials to do sub-group analyses and answer the question he has proposed (see OPERA I & II data below).
These issues also apply to paediatric or childhood MS. In response to the latter, the FDA and EMA now mandate as part of the licensing process that Pharma have to do paediatric trials as part of their post-marketing commitments. Should the regulators be doing the same for the ethnic minority groups? Maybe, but this would come at a cost. Post-marketing commitments are expensive and their costs are built into the drug pricing. Do we want more expensive DMTs? A better solution would be to rely on real-world evidence collected in a systematic way via national and regional registers. I have little doubt that registry data will be able to tell us if ‘non-white’ pwMS respond or not to DMTs.
This editorial will not change our practice. We treat people with active MS who are from ethnic minorities in the same way we treat Caucasian pwMS. Why wouldn’t we? Lack of evidence does not mean lack of efficacy. In my experience pwMS who are from an ethnic minority background respond as well to high efficacy DMTs in terms of treating-2-target of NEDA than Caucasian pwMS. What tends to happen is that they are more likely to end up at the top of the treatment pyramid on one of the monoclonals. The reason for this is that they probably need these higher efficacy DMTs because they have more active MS. Should we rely on anecdotes? Probably not, I suggest we and others audit our data and get back to you on this specific question.
Avasarala. FDA-approved drugs for multiple sclerosis have no efficacy or disability data in non-Caucasian patients. CNS Spectr. 2019 Jan 3:1-2. doi: 10.1017/S1092852918001517.
Pharmacotherapy of multiple sclerosis (MS) is evolving rapidly. Despite impressive gains over the past 2 decades in the approval of multiple drugs for MS, lack of recruitment of minorities with MS in phase 3 clinical studies is a persistent concern and skews efficacy and disability data.
CoI: multiple
Prof G, what has happened to your Barts-MS research days? They were always something my partner and I looked forward to attending. Are you planning to hold one again this year? Thanks.
Yes, UCL were meant to host it in 2017 and let it slip. Then they promised to host in 2018 and nothing happened. This was all under the so called MS@ULCP (UCL Partners) umbrella. These events take enormous resources and time.
Are you prepared for something cheaper and more accessible this year? Any ideas?
Why not host regular Hangouts like the one you do from ECTRIMS? You crowdsource ideas and open up the discussion to us readers.
Good idea. I will run it past the team and see if they are up for it.
Our UCL partners who had been organising this..flaked outOur one last one was in Stornaway in the Outer hebrides. The videos are on YoutubeFor this year we were thinking of Malta…Why because we were being asked to teach medical students there…but I am not sure if this (the teaching) is going ahead. Dang I was looking forward to a holiday in the Sun.
Use the search term 'Stornoway' and not 'Stornaway' to find all the talks on the blog or on the Barts-MS YouTube channel.
newver was good at spellin:-)
Thanks Prof G. Great article. Could the reason for more active Ms in ethnic minorities be becuase EBV is more active in ethnic minorities due to less historical exposure to the virus?
Not sure about EBV in ethnic minorities living in high MS prevalence countries. Something we will look into as part of our #PreventMS programme.
There is evidence that older people, males and non-whites tend to be diagnosed with PPMS, which we know does not respond well to DMT. But to suggest they do not respond I think is rather rash without solid evidence and makes no biological sense.The Japanese tend to do trials in Japanese people with the new MS drugs and what do they find.., yep you guessed it they work just the same as in non-whites.Is the immune system fundementally dependent on skin colour the answer is no. Sure if I look at a C57BL/6 mouse it has black fur and does worse than an ABH or SJL mouse (it has white fur) but a DBA-2 (grey fur) is low susceptibility like a NOD mouse (White fur) as is a C57BL/10 that has black fur. But cross a C57BL/10 (resistant black fur) with a PL/J (susceptible white fur) and you get a C57BL/10.PL (susceptible black fur)…Then we could do eye colour pink eyes verses brown eyes What a pile of nonsense what next an editorial to say there are fewer LBGT in trials also. If we understand the pharmacogenetics then indeed some populations may be different than others. Dr M&M spotted that a gene variant (Missense. rs77928789) of CD52 was more commmon in hispanics/Latino (0.1931 about 1 in 5 people) than non-hispanics (finish people is 1 in 10.000), does it after alemtuzumab responses I don't know. but if importnat there could be population differences. But if someone does not respond you switch them. It would be pretty obvious in our multicultural base of pwMS who on subgroup does not respond at all.
Have heard from DrK and we have looked and in our small sample and the answer is to the question what a load of second-largest branch of Islam after sunni spoken by Liam Gallageher (Oasis) with a Manchester Acent:-)So thanks to Dr. Avasarala…..we will soon see a flurry of papers