What does your DMT say on the tin?
Some advice on what to say to your neurologist, or HCP, the next time you see them; “I now know why I am not expecting to get anything more out of this DMT than what it says on the tin”.
Our current crop of DMTs can only do what they are designed for, i.e. stopping the focal inflammatory activity or new lesions from forming. They are not designed to switch-off smouldering MS, restore neurological function or scrub the brain clean of the damaging B-cells and plasma cells. Based on this we need to readjust our treatment goals for DMTs.
This is why one of my #ECTRIMS2019 highlights was as a post-hoc analysis that showed the best predictors of treatment response to natalizumab was (1) MRI activity (Gd-enhancing lesions and new T2 lesions), (2) neurofilament levels and (3) relapses. All the other factors did not contribute anything to predicting treatment response. Why not? The answer lies in the biology of MS. Relapses, focal MRI activity and raised neurofilament levels are the triumvirate of inflammatory disease activity.
Calabresi et al. Disease control beyond NEDA: The value of non-clinical disease activity measures to determine treatment response to natalizumab. ECTRIMS Online Library. Calabresi P. Sep 13, 2019; 278615; P1415
Based on the analyses in this poster our treatment goal with anti-inflammatory DMTs should be NEDA based on these three variables. All the other factors (EDSS, 9HPT, 25TW, BVL, PASAT) that we analysed added zero to the predictive model. The reason for this is that all these additional variables measure disability worsening or end-organ damage that is the consequence of the previous inflammatory activity.
This is why we should not expect our DMTs to do more than what they are designed to do. If you want to prevent worsening from occurring you have to get your MS treated early and effectively and prevent the accrual of early damage.
Another message from this analysis is that relapses were the weakest member of the triumvirate; MRI and NFL levels trumped relapses. The implications of this are that you need to have your disease activity monitored; yes, measured on a regular basis. If your neurologist suggests that you don’t need an MRI, or in the future peripheral blood NFL measurements, can I suggest you tell them they are wrong?
Another implication of this study is potentially a cut-off for what is an acceptable peripheral blood neurofilament level, i.e. you need your NFL levels kept below 8pg/mL. This cut-off will separate the ‘men from the boys’; the only DMTs that are effective enough to reduce average levels consistently below this point are the high efficacy DMTs.
One final message. Natalizumab continues to teach us about MS. It is the one drug that has transformed MS in so many ways and it has taught me more about MS than anything else. As I have said before there are two phases to the history of MS; the phase before natalizumab and the phase after natalizumab.