The risk of Lemtrada is that is going to cause (a) neutralizing antibodies that can stop it working and (b) unwanted and sometimes life-threatening (if not detected quick enough) autoimmunities. This occurs in 20-40% of MSers within a few years of treatment. The docs at Cambridge have been investigating this and have ways to stop the neutralising antibodies and have found a marker they think shows your risk of developing autoimmunity. This type of study has not been reported of the phase III trials....With a large sample one could have seen if this had mileage as a pre screen to mitigate risk...
What do the manufacturers do about this?.....well apparently nothing!
They just make you get checked up every month for 5 years to check for the autoimmunities notably a platelet disease and thyroid disease. Heaven forbid that you don't take their drug because they can deal with the autoimmunities.
What did the interferon manufacturers do to sort out who was one the 30% responders......well nothing as they could sell the inactive drug to 70% others. Some call it Bad Pharma others call it Phamacoeconomics.
In the second pape an ELISA that detected soluble interleukin 21 was used and was suggested to predict, in part, whether autoimmunity may develop after alemtuzumab treatment. An ELISA against interleukin 21 is may contain a capture IL-21 antibody that is stuck to plastic and a detect anti-body that has a dye attached to it. So you add blood which contains IL-21 that is bound to the capture antibody and then you add the detect antibody that can now bind to the captured IL-21 and the more IL-21 in the blood the more that is captured the more detection signal you get. You then take a known amount of IL-21 and put this in the assay and then you can work out how much is in the blood. You can make these ELISAs up or eventually a company will make a kit, which is easier to do and generally gives more consistent results. This study tests a few commercial kits and none of them performed as well as the original ELISA and they had n predictive value. There are clearly problems with the ELISAs as they are not accurately detecting the levels in the blood ~500pg/ml in one verses 50pg/ml.
The New mantra from academia is personalised medicine...however are pharma going to invest much to work out who will not benefit from drugs and who will not?....Is not phamacoenconomics to not sell drug. Likewise who will benefit from the drug.
One would think that people early in disease have most to gain, but may not take the risk. But those with disability may be be more willing to take the risk......but will it work. The manufacturer could I guess work this out in relation to say ability to induce NEDA and prior disease duration.
Whilst IL-21 may make a prediction of who will get autoimmunity as can be seen it is not predictive of who will and who will not get autoimmunity as there is a lot of overlap(seen in the graph). This is an example were you could test sensitivity and specificity.