There are two main reasons for stopping an MS drug: 1) it no longer works for you i.e. there is break through disease activity, in which case you should be on a better drug, or else 2) it no longer works for you as you have now entered the progressive stage of your disease. The latter has proven very difficult to define clinically and radiologically, making it harder to know exactly when to stop the immunosuppressive treatment. You may have noticed that when you asked your neuro about this, the reply may have well been ‘don’t know’ or a confused regurgitation of evidence from natural history studies on whether it’s a good idea or not.
The reality of the matter is that we do not know in a clinically meaningful way when the inflammatory phase of MS stops. The progressive phase of the disease can start as early as when you first note walking difficulty, cognitive/memory problems or bowel/bladder dysfunction. And often what you find is that they co-exist together.
Previously, in a large retrospective study carried out by the MSBase Registry group it was noted that those with RRMS on injectables with no relapses for +5y, in those that stopped treatment there was no difference in those who continued in terms of time to the next relapse compared to those who didn’t, but in those who stopped, the time to disability progression was shorter. And this is because the two phases, inflammation and progressive disease are intertwined in MS. Secondly in those who had entered secondary progressive MS (disease stable for 2-20y) and stopped their treatment, 11.7% had a resurgence of their disease activity, but this occurred in an even larger proportion (58.8%) in the relapsing-remitting population who stopped their drug. When they studied specifically those with secondary progressive MS older than 60y they noted that in those 29.7% of those who stopped their treatment, only one relapsed. So, it is potentially possible that it’s safe to stop treatment after the age of 60.
This study from Italy looks at stopping interferon-beta in those with secondary progressive MS. They enrolled those who had evidence of walking limitation (EDSS 4.0) to requiring a stick (EDSS 6.0). They then studied the time to reach an EDSS score of 7.0 (individual who is unable to walk beyond approximately 5 m even with aid and is essentially restricted to a wheelchair). The participants also had to have absence of clinical or radiological activity for at least 24 months i.e. non-active SPMS.
What they found was that when the interferon-beta was stopped (Group A), there was no appreciable difference from those who didn’t stop (Group B) in reaching an EDSS score of 7.0 (see Figure below). During the study, six patients (four in group A and two in Group B) had clinical relapses, with a median time of 17.6 ± 7.9 in Group A and 15.8 ± 6.8 months in group B. Seven had radiological activity (three in group A and four in group B 14.5 ± 6.5 and 15.1 ± 5.8 months).
What does this all mean if you’re a patient on interferon-beta who has just been given a diagnosis of SPMS? If this is you and your scans have been stable for at least 24 months then chance of the MS inflammatory activity returning is low (~2%) according to this study. Of course the evidence for stopping a more highly active maintenance treatments is not there and will be more complicated than stopping a first-line MS treatment e.g. rebound activity. The pros and cons of stopping MS treatments in progressive MS therefore needs to be discussed carefully.
Stopping Interferon Beta 1b Does Not Influence the Risk of Disability Accrual in Non-Active SPMS: Results from an Italian Real-World Study
Background: No consensus exists on the possibility to stop disease modifying therapies (DMTs) in Secondary Progressive Multiple Sclerosis (SPMS).
Methods: The primary outcome was the time to reach 24-weeks confirmed Expanded Disability Status Scale (EDSS) 7.0. We enrolled all patients with a confirmed diagnosis of non-active SPMS (here, absence of clinical or radiological activity for at least 24 months before the conversion) between 1 January 2010 and 31 December 2015, at MS centers of Catania and Foggia, Italy. Patients were divided into two groups, according to the shared decision to stop DMTs (group A) or to maintain/switch to licensed interferon beta 1b for SPMS (group B). A Cox model adjusted with an inverse probability weighted propensity score (IPTW-PS) was employed.
Results: A cohort of 311 patients was enrolled, 165 were in group A and 146 were in group B. Patients in the two groups were similar for baseline characteristics. The IPTW-PS adjusted Cox model for the event time to 24-weeks confirmed EDSS 7.0 did not show differences between the two groups (ExpB 0.96, CI 0.739-1.271, p = 0.819).
Conclusions: In a real-world setting, in patients with non-active SPMS, the maintaining or switching to the licensed interferon beta 1b did not reduce the risk of reaching confirmed EDSS 7.0.