The debate about what is active and inactive secondary progressive MS will not be settled by the EMA adopting a positive opinion, recommending the granting of a marketing authorisation for siponimod, which is now ‘licensed’ for the treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease. Siponimod reduces disability progression in people with active SPMS. The most common side effects are headache, hypertension and increased liver enzyme levels. The full indication is: “treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity (see section 5.1)”.
This label will disappoint the many pwSPMS who don’t have active scans and therefore won’t be eligible for DMTs. I have commented on what is and is not active SPMS in the past. I think the siponimod label entrenches the MRIcentric worldview of what is active MS. We know that the majority of people dying with SPMS have ongoing inflammation in their brains and spinal cords at post-mortem. Try telling someone with SPMS who is getting worse that they don’t have active MS because they have no enhancing, or new or enlarging T2, lesions on MRI. And what about using CSF and/or peripheral blood neurofilament levels to assess activity? We clearly need to challenge the EMA’s and FDA’s definitions of what is active SPMS.
At least the licensing of siponimod for treating SPMS is a big positive for the field and indicates that we are beginning to address the unmet need in treating more advanced MS.
The impact that this will have on our MS services should not be underestimated. We are now going to have to monitor our SPMS patients with annual MRI scans. Do we have the resources for this? What about the extra follow-up clinic slots? This alongside ocrelizumab for active PPMS is going to put a major strain on our MS services. Will our managers give us more resources?
Siponimod may not be an eagle, phoenix or maven, but rather a hopebird which symbolises the importance of “an optimistic approach to what lies ahead” and why it is important to have a “glass half full” attitude. Less than a decade ago we were telling our patients with a progressive course that they were beyond hope, that has now changed.