Secondary progression — what is really new?

I was invited to speak at the neurology round in Cambridge this week on advancing/worsening MS (aka secondary progressive MS). I got a mixed response from my talk (you can view my slides online or download them).

The general consensus was that there is nothing really new in the length-dependent axonopathy and asynchronous progressive MS hypotheses. I agree; the essence of the hypotheses are clearly articulated by John Kurtzke’s insightful diagram published in 2015, which he sketched out in the 1960s. I reminded my audience that there are very few if any original ideas. All I did was reformat the data and present it with different emphases.

However, I disagree that there was nothing new. What is new is the reinterpretation of old data from progressive clinical trials and new data that clearly demonstrate that more advanced MS is modifiable. This is in stark contrast to the mindset of a therapeutic window, a concept that quite possibly originates from Cambridge, which labels people with more advanced MS as being too far gone to benefit from anti-inflammatory therapies. We simply didn’t have the necessary insights we have now to design progressive trials to give us a realistic chance of a positive outcome.

Now that we know how to design and perform progressive MS trials we are extending them into advanced MS, even into wheelchair users, to delay or prevent the loss of arm and hand function. This is why I am so proud to be involved with the ORATORIO-HAND and CHARIOT-MS trials. I sincerely hope these trials prove the doubting Thomases wrong and more importantly deliver hope to people with more advanced MS.

An important point that was not really acknowledged was that to tackle progressive MS you need to start somewhere and that having an anti-inflammatory platform to build a combination therapy pyramid on top of is a very important start. Therefore I cannot emphasise more, why the ocrelizumab PPMS and siponimod SPMS results are so important for the field. I would go as far as saying they are both landmark studies and we will be discussing the field of primary progressive MS as pre- and post-ocrelizumab and the field of secondary progressive MS as pre- and post-siponimod.

If sister 2 who I wrote about in my Variance post attended this meeting I wonder what she would think? Would she be upset with the persistent ‘therapeutic nihilism’ that exists about treating more advanced MS? Would she leave the meeting filled with hope that there is at least a treatment on the horizon for SPMS? Or would she still be depressed about having been misdiagnosed, treated with a platform therapy, delayed access to high-efficacy treatments, allowed to develop SPMS and now having her DMT stopped because of NHS guidelines? What do you think; have your say?

CoI: multiple