“A critical issue in MS with regard to risk:benefit assessment of DMTs (disease-modifying therapies) is the short-change we give to the risk of MS. This real-life data study below shows that when we de-risk PML by taking MSers off natalizumab, we increase their risk of becoming more disabled. If you are on natalizumab and stop the drug your have two-fold higher risk of getting worse compared to MSers who stay on natalizumab. More importantly if you stop natalizumab you are likelihood of having an improvement in disability plummets and is 68% lower than MSers who stay on natalizumab.”
“This study is telling us several things:
- How are expectations have shifted since we have licensed high-efficacy DMTs; we are not only expecting MSers to flatline (no increase in disability), but expect a significant proportion of MSers to have a sustained improvement in disability.
- Your baseline disability level predicts worsening. In other words if you have lost time, or brain, you are more likely to progress when coming off natalizumab. This makes sense biologically. What protects from developing progressive MS is reserve capacity; if your nervous system has not lost too many neurons and axons the surviving cells have the ability to compensate.
- Natalizumab is not an induction therapy; it is a maintenance therapy. In other words when you stop natalizumab MS comes back with a vengeance. Some observations suggest the rebound with natalizumab is much worse than you would expect from natural history studies. Natalizumab is an interesting observation.
Previous posts of interest:
- , 20 Aug 2014
- , 06 Aug 2014
- , 05 May 2014
- , 07 May 2014
OBJECTIVE: The objective of this paper is to estimate the risk of reaching well-established disability milestones after withdrawal of natalizumab (NTZ) due to concern about the risk of progressive multifocal leukoencephalopathy in MSers.
METHODS: Data from 415 MSers followed-up for six years after starting NTZ were collected from seven tertiary MS centres. The risk of disability worsening, i.e. reaching Expanded Disability Status Scale (EDSS) scores of 4.0 or 6.0, and the likelihood of experiencing a disability reduction of one EDSS point (or more), were assessed by propensity score-adjusted analyses in MSers who discontinued and in those still on treatment at the end of follow-up.
RESULTS: A total of 318 MSers who received standard NTZ treatment without experiencing evidence of disability worsening in the first two years were included in the six-year follow-up analysis, with 196 (61.6%) still on treatment and 122 (38.4%) discontinuing after a median time of 3.5 years. MSers in the discontinuing group had a more than two-fold increased risk of disability worsening (p = 0.007), and a 68% decreased likelihood of experiencing disability reduction (p = 0.009) compared with the continuing group.
CONCLUSION: While discussing the overall risk/benefit profile of NTZ, MSers should be advised that, in case of treatment discontinuation, the risk of disability worsening is one in three, and increases to one in two if the EDSS score at NTZ start is above 3.0.