Friday, 6 June 2014

Clinic Speak: post natalizumab don't mix steroids and glatiramer acetate

GA and IFN-beta simply not good enough post-natalizumab. #ClinicSpeak #MSBlog #MSResearch

"This study confirms what we already know that IFN-beta and GA are not good enough, on average, to prevent rebound on weaning natalizumab. What is interesting is that MSers switched from natalizumab to GA combined with pulsed monthly steroids did worse than those switched to GA alone. This may indicate that steroids interfere with the mode of action of GA. In summary when switching from natalizumab to other DMTs you need to go onto a higher efficacy DMT to prevent rebound. The data is strongest for fingolimod. The data also supports no wash-out, i.e starting fingolimod within 4 weeks of the last natalizumab infusion. This allows the fingolimod to be active prior to natalizumab dropping to sub-therapeutic levels."

"IFNbeta and GA don't prevent rebound in the majority of cases. Why? Several reasons. Firstly, a large number of MSers have already failed these drugs and are therefore non-responders. So why should they become responders later on. Secondly, these drugs take longer than 2 months to have their maximum impact. A two month onset of maximum therapeutic efficacy will be necessary to prevent rebound. Finally, IFNbeta and GA are simply not effective enough. What about emerging therapies BG12, teriflunomide and alemtuzumab? We simply don't have enough data. I suspect teriflunomide and BG12 may not have enough efficacy and as they don't cause a large lymphopaenia they may not be able to prevent post-natalizumab rebound. Alemtuzumab is another story; I suspect it will prevent rebound but as it is an induction therapy and irreversible you need to make sure that there is no chance of carry-over PML; i.e. asymptomatic PML on natalizumab that manifests itself months after stopping the drug. I have posted on this subject recently and the issue surrounding this practice are complex."

Switching from fingolimod to alemtuzumab #ClinicSpeak #MSBlog #MSResearch


Epub: Rossi et al. Treatment Options to Reduce Disease Activity After Natalizumab: Paradoxical Effects of Corticosteroids. CNS Neurosci Ther. 2014 May. doi: 10.1111/cns.12282.

BACKGROUND: Natalizumab (NTZ) discontinuation leads to MS recurrence, but represents the only known strategy to limit the risk of progressive multifocal leukoencephalopathy (PML) in JCV seropositive MSers. Here, we compared the clinical and imaging features of three groups of MSers who discontinued NTZ treatment.

METHODS: We treated 25 MSers with subcutaneous INF╬▓-1b (INF group), 40 MSers with glatiramer acetate (GA group), and 40 MSers with GA plus pulse steroid (GA+CS group).

RESULTS: Six of 25 MSers (24%) of the INF group were relapse-free 6 months after NTZ suspension. In GA group, a significant higher proportion of patients (26 of 40 patients, 65%) were relapse-free (P < 0.05). Far from improving the clinical effects of GA in post-NTZ setting, combination of GA+CS was associated with lower relapse-free rate than GA alone (40% vs. 65%, P = 0.04). Also on MRI parameters, combination of GA+CS was associated with worse outcome than GA alone, as 22 of 26 subjects (84.6%) had MRI evidence of disease activity 6 months after NTZ discontinuation.

CONCLUSION: Corticosteroids should not be used in combination with GA to prevent post-NTZ disease recurrence.

CoI: multiple

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