I wouldn’t taper natalizumab to prevent rebound; there is no scientific rationale. #ClinicSpeak #ResearchSpeak #MSBlog #MSResearch
“The study below suggests that if you taper natalizumab treatment by having 2 further infusions at week 6 and then at week 14 you are less likely to have relapses on your new DMTs (milder rebound) compared to those who stop natalizumab suddenly and transition to a new DMT (rebound). What the author’s don’t tell you in the abstract that period of washout after natalizumab was highly variable (1-6 months) and the DMT you transitioned onto also varied (interferon, GA, fingolimod, dimethyl fumarate or teriflunomide). We know now that both these factors are critical in preventing rebound post-natalizumab. The washout period should be less than 4 weeks if possible and no more than 8 weeks and the only DMTs that reliably prevent rebound are fingolimod and rituximab (off-label and not available in the NHS).”
“In short very few conclusions can be drawn from this study and in my opinion there is nothing here that makes biological sense. Retrafficking of lymphocytes into the CNS has to do with the level of saturation of VLA-4 on the surface of the circulating lymphocytes; a tapered withdrawal of natalizumab will simply delay the desaturation kinetics of VLA-4 and hence the time to re-trafficking and the subsequent rebound. The tapering strategy won’t prevent rebound activity unless it took the new DMT longer than 3-4 months to have a treatment effect. If that was the case a better strategy would be start the new DMT before stopping natalizumab to allow it start working by the time natalizumab was out of the system. I suggested this study design some time back in relation to using DMF, and teriflunomide, post-natalizumab.”
Weinstock-Guttman et al. Randomised natalizumab discontinuation study: taper protocol may prevent disease reactivation.J Neurol Neurosurg Psychiatry. 2016 pii: jnnp-2015-312221.
OBJECTIVES: To compare two modes of natalizumab cessation interventions: immediate versus tapered down, as measured by serial MRI and the occurrence of relapses during a 12-month period.