Rebound vs carry-over PML. What risk are you prepared to accept? #MSBlog #MSResearch
"This study on Natalizumab withdrawal supports yesterday's post on rebound. Despite the study below being so small it shows that rebound occurs. A similar thing happens with glatiramer acetate. The message is if you have highly-active MS and need to be on a high-efficacy drug such as natalizumab you probably need to switch to a high-efficacy replacement. The most dangerous thing about doing this is that if you are JCV+ve, there is the possibility of carry-over PML. Carryover PML is a particular problem for drugs you can't reverse. For example, once you have been treated with alemtuzumab you can't reverse its treatment action. It is quite a powerful immunosuppressive agent in the first few months after treatment, that is until the immune system reconstitutes, if you develop carry-over PML in this window when your immune system may be too weak to fight PML, the consequences could be fatal. Fingolimod on the other hand can be stopped and washed out over a period of 6-8 weeks, but even 6-8 weeks is a long time in the life of someone with PML. The bottom line is you need to be confident that there is no carryover PML, which is why we insist on doing lumbar punctures and an MRI. Safety first."
BACKGROUND: Natalizumab (NTZ) discontinuation leads to multiple sclerosis reactivation.The objective of this study is to compare disease activity in MSers who continued on NTZ treatment to those who were switched to subcutaneous interferon 1b (IFNB) treatment.
METHODS: 1-year randomized, rater-blinded, parallel-group, pilot study (ClinicalTrial.gov ID: NCT01144052). Relapsing remitting MSers on NTZ for ≥12 months who had been free of disease activity on this therapy (no relapses and disability progression for ≥6 months, no gadolinium-enhancing lesions on baseline MRI) were randomized to NTZ or IFNB. Primary endpoint was time to first on-study relapse. Additional clinical, MRI and safety parameters were assessed. Analysis was based on intention to treat.
RESULTS: 19 MSers (NTZ n=10; IFNB n=9) with similar baseline characteristics were included. 78% of IFNB treated patients remained relapse free (NTZ group: 100%), and 25% remained free of new T2 lesions (NTZ group: 62.5%). While time to first on-study relapse was not significantly different between groups (p=0.125), many secondary clinical and radiological endpoints (number of relapses, proportion of relapse free patients, number of new T2 lesions) showed a trend, or were significant (new T2 lesions at month 6) in favoring NTZ.
CONCLUSIONS: De-escalation therapy from NTZ to IFNB over 1 year was associated with some clinical and radiological disease recurrence. Overall no major safety concerns were observed.
CoI: multiple