There is still a lot of confusion regarding the assignment to a specific MS course type. Generally, a distinction is made between relapsing (RMS), secondary chronic progressive (SPMS) and primary chronic progressive (PPMS) multiple sclerosis. These descriptions of the clinical course are still influenced by the pre-MRI era and therefore also of little help when it comes to modern treatment decisions. Nevertheless, the above classification still determines the indication of the different MS medications. Thus, the vast majority of available MS drugs have been approved only for the treatment of the relapsing course form.
As early as 2013, an international panel of experts dealt intensively with the problem of MS classification – the very readable results of the discussion were published in 2014 in the renowned journal NEUROLOGY (Lublin et al. Neurology 2014;83:278–286). Accordingly, the experts do advocate for maintaining the core phenotypes of MS – that is, the classification into relapsing or progressive MS. However, they see a significant addition to the classification in determining whether it is an active disease. Disease activity as an important characteristic is defined by relapse activity or the occurrence of new MRI lesions (either contrast-enhancing T1 lesions or new T2 lesions). According to the experts, this significant addition should not determine access to MS therapy based on the stage of the disease, but primarily on the activity of the disease. In my view, this is absolutely sensible.
Very slowly, this concept is also starting to assert itself in terms of drug approvals. The European Medicines Agency EMA has explicitly approved the new active ingredient Siponimod (Mayzent) for use in secondary chronic progressive patients with active disease. Although this is far from being as progressive as the decision by the American FDA, which has approved Siponimod for all active forms of MS (see also article “Approval of Siponimod in the USA and Europe – the vote of the regulatory authorities“), it is ultimately moving in the right direction. Because fundamentally, it would make sense to enforce a “label extension” for all anti-inflammatory substances, so that drugs that currently only have approval for relapsing MS are also approved for active MS, regardless of the stage of the disease. Such a rethink would simplify a lot – for doctors as well as for patients.
So how do you define active MS? Primarily – as already indicated above – by the occurrence of new relapses and new MRI lesions. Therefore, regular MRI checks and the comparability of MRI images are very important, as this can well demonstrate disease activity. I would even go a step further – an increase in disability progression, cognitive disorders or fatigue symptoms can also indicate an active disease. That’s why regular checks of the neurological examination findings, cognitive performance and regular self-reports from patients about fatigue are so important. And of course, great hopes also lie in new technical innovations such as new MRI technologies, biomarkers and OCT (Optical Coherence Tomography).
At present, patients with secondary chronic progressive MS who wish to be treated with Siponimod usually present themselves, who have not had MRI examinations for years, where no clinical preliminary findings such as walking distance or hand function are documented, let alone cognitive tests or fatigue questionnaires in progress. In such cases, it is very difficult to prove an “active” disease. Just the information that it is “getting worse” is not enough, because that is only the general characteristic of a progressive disease.
These considerations on the approval of Siponimod are primarily a plea for regular and comprehensive monitoring of MS patients throughout the course of the disease, because only in this way can “active” patients be identified.
