Epub: La Mantia et al. Interferon β for secondary progressive multiple sclerosis: a systematic review. J Neurol Neurosurg Psychiatry. 2012 Sep 5.
METHODS: Using Cochrane methodology, we reviewed all randomised placebo controlled trials of IFNβ in SPMSers (1995-March 2012).
RESULTS: 5 trials (3082 MSers) were included. After 3 years, interferons did not reduce disability progression, confirmed at 6 months (RR 0.98, 95% CI 0.82 to 1.16). A small reduction in the number of MSers who had relapses during the first 3 years of treatment (RR 0.91, 0.84 to 0.97) was found. No analysis of cognitive data was possible. More treated than placebo MSers dropped out for adverse events.
CONCLUSION: 3 year treatment with IFNβ does not delay permanent disability in SPMS but reduces relapse risk, indicating that the anti-inflammatory effect of IFNβ is unable to prevent MS progression once it has become established.
BACKGROUND: It is unclear whether recombinant β interferons (IFNβ) can be effective in secondary progressive MS (SPMS). The aim was to determine whether IFNβ can reduce the risk of disability and cognitive impairment progression in SPMS.
METHODS: Using Cochrane methodology, we reviewed all randomised placebo controlled trials of IFNβ in SPMSers (1995-March 2012).
RESULTS: 5 trials (3082 MSers) were included. After 3 years, interferons did not reduce disability progression, confirmed at 6 months (RR 0.98, 95% CI 0.82 to 1.16). A small reduction in the number of MSers who had relapses during the first 3 years of treatment (RR 0.91, 0.84 to 0.97) was found. No analysis of cognitive data was possible. More treated than placebo MSers dropped out for adverse events.
CONCLUSION: 3 year treatment with IFNβ does not delay permanent disability in SPMS but reduces relapse risk, indicating that the anti-inflammatory effect of IFNβ is unable to prevent MS progression once it has become established.
At the progressive stage of the disease, it is being argued (quote NationalMSSociety) that the Tk cells do no longer cross the BB Barrier (MRI show no Gd+ lesions). This is the reason why new treatments (Ocrelizumab, f.e), are being studied under intrathecal administration. Would this also explain why Interferons do not work any longer in the progressive phase?
I actually meant Rituximab, not Ocrelizumab… Sorry for that
if only we knew what was driving progression I could answer this question. The reason for the intrathecal administration is the belief that the B-cell follicles, with or without EBV, are driving secondary progression. We have many posts on this topic. Who knows rituximab and interferon-beta may both be working against EBV with the former being more effective. Time will tell!
This sort of study is so important and yet seems to have little traction in influencing prescribing guidelines.Does the medical pharma lobby inhibit a proper conversation on this matter?Time and time again it seems that the end results of disability accruel are not significantly altered by the first tier DMTs. But if you want to get an alternative DMT prescribed you are told: you have to fail first line DMTs first. In other words – you HAVE to get disabled in order to get treatment that stops disability.It makes you want to weep.
It's studies like this that will change prescribing guidelines. Now the new DMTs show a significantly greater effect on reducing relapses they will become more commonly prescribed and Beta interferon may shuffle off the scene. That being said, what is becoming more and more apparent is that just reducing relapses will probably not be good enough to stop progression (though it should slow it down) and what we need is also to be giving neuroprotective agents as well as DMTs. This belt and braces approach should significantly improve the situation for MSers and neuroprotectants are one of our main focuses.
If one had to guess (bearing in mind we don't understand the full mechanism of most/all DMDs) which current DMD (i.e. phase 3 or beyond) would you guess is most 'primary' neuroprotective (as opposed to secondary neuroprotective via reducing inflammatory attacks)? BG12? Laquinimod/Teriflunomide? Alemtuzumab?
GOOD QUESTION, MAN.
No guessing allowed. We need to know what drives secondary progression and target that. This is what we are trying to do with our neurofilament LP study.