Most of you will have heard by now that NICE has green-lighted siponimod for the treatment of active secondary progressive multiple sclerosis on the NHS. As the UK member of the EXPAND trial steering committee, Novartis who market the drug asked me for a quote, which sums up my opinion about the news.
“The NICE approval of siponimod to treat secondary progressive multiple sclerosis with active disease is a landmark that promises to transform the way we view and manage MS. At last, we have a treatment that can modify the progressive pathology that underpins secondary progressive MS with active disease. The ‘Forgotten Many’ is how people with secondary progressive multiple sclerosis have described themselves; but not anymore. Our challenge is to configure our NHS services to treat patients with secondary progressive MS and to manage expectations, as not all people with secondary progressive multiple sclerosis will be eligible for siponimod. However, this is the beginning of a new era in the management of MS and should be celebrated for that.”
Here we go again. Most readers will have gathered by now that NICE has not recommended Siponimod for treating active SPMS under the NHS. This is a big disappointment for the MS community in the UK particularly for those patients who have active SPMS or worsening SPMS on a DMT who were hoping to be switched to Siponimod.
It is clear that some of the assumptions NICE have made about the treatment of MS don’t represent the reality on the ground, in particular, that most people diagnosed with SPMS do not have any disease-modifying treatment. I would argue that the biggest population of potential ‘siponimod-eligible’ patients with SPMS are those smouldering away on existing DMTs. A straw poll of UK MSologits we did in 2014 indicated that most were reluctant to label their patients as having SPMS because of the implications it has for treatment. Most MSologists don’t necessarily stop existing DMTs in patients with worsening disability because they are concerned about the potential for a rebound in inflammatory disease activity.
1.1 Siponimod is not recommended, within its marketing authorisation, for treating secondary progressive multiple sclerosis with evidence of active disease (that is, relapses or imaging features of inflammatory activity) in adults.
1.2 This recommendation is not intended to affect treatment with siponimod that was started in the NHS before this guidance was published. People having treatment outside this recommendation may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS healthcare professional consider it appropriate to stop.
Why the committee made these recommendations
Interferon beta-1b is the only disease-modifying treatment available for people with active secondary progressive multiple sclerosis. However, few people take it.
Most people do not have any disease-modifying treatment. Clinical trial results show that siponimod reduces the number of relapses and slows disability progression compared with placebo. It is uncertain how effective siponimod is compared with interferon beta-1b because there is no evidence directly comparing them.
Because of the limited clinical evidence, the cost-effectiveness estimates are uncertain, and none of the analyses reflect the committee’s preferred assumptions. Therefore, siponimod is not recommended.
The idea that MS is three diseases rather one disease is clearly coming back to haunt the field. I think most people working in MS understand that MS is one disease with superimposed inflammation, i.e. relapses and focal MRI activity, determining the clinical phenotype and being the treatment target for licensed anti-inflammatory agents such as siponimod. The question about whether or not focal inflammation drives all pathology has yet to be answered, but based on the early treatment trials of highly-effective agents this seems likely.
As always we as an MS community are going to have to respond to NICE. But what do we say? I am not sure there is a consensus amongst UK neurologists about how we diagnose and manage SPMS. The following are a series of questions that I think need to be answered when it comes to managing pwMS who are ‘transitioning to’ or have become secondary progressive, which will inform the content and tone of our response to NICE. As always our role as MSologists and MS HCPs is to be patient advocates; I sincerely hope we won’t let you down.
What components of ‘disease activity’ do you think should define active SPMS?
What timeframe should be used to define active SPMS?
Do you actively screen for and diagnose SPMS in patients on DMTs?
Do you actively avoid diagnosing SPMS so that you don’t have to stop their DMT?
Do you generally stop DMTs in patients who have transitioned to becoming secondary progressive?
What concerns you when stopping DMTs in patients who have transitioned to becoming secondary progressive?
Do you think it is appropriate to stop DMTs in patients who have transitioned to becoming secondary progressive to see if they become active?
Do you start or switch patients who you have diagnosed as having active SPMS onto interferon-beta-1b according to NHS England’s or other guidelines?
Do you have any patients under your care who have become secondary progressive on DMTs who are now wheelchair-bound (EDSS>6.5)?
