ClinicSpeak: improvement in function occurs when you stop inflammation

Do injectable DMTs have a future in the treatment of MS? #MSBlog #MSResearch #ClinicSpeak

Improvement in walking speed on natalizumab #MSBlog #MSResearch #ClinicSpeak

"The study below shows that MSers on natalizumab, a highly-effective DMT, improve; their walking speed gets better. This supports many others studies demonstrating an improvement in function in a proportion of MSers on natalizumab across several neurological subsystems, i.e. vision, bladder, upper-limb function, fatigue, cognitionm etc. Why natalizumab? It is almost certainly because it is a highly-effective DMT and renders the majority of subjects NEDA once they  have been on the drug for more than 12 months. Is this observation specific for natalizumab? No we also see this result with alemtuzumab and BMT (bone marrow transplantation), i.e. other highly-effective treatments. Why does this not occur on lower efficacy drugs? It does, but a much small number have improvements, because the the responders tend to be hidden in a sea of non-responders. If only we could determine responder status prior to starting a DMT it would allow us to optimise the sequencing of DMTs to derive the maximum benefit with the best safety profile for the treated population. I am  surprised that the Pharma companies that produce, and market interferon-beta, blinked. We have known for a decade or more that a type 1 interferon signature in the peripheral blood at baseline predicts a poor response to interferon beta. This finding has been replicated by several groups. Why didn't Pharma validate it in a controlled trial? If they did we interferon-beta may be with us for decades and beyond."

"I was asked by a neurologist in Hyderabad if I saw injectables surviving the onslaught of the oral DMTs. I said yes, firstly they are safe and some of us are now using them in pregnancy; the orals are too new for us to be confident about their safety in pregnancy and at least two are know to be teratogenic (teriflunomide and fingolimod). Secondly, many markets are price sensitive and as the injectables are cheaper than the newer therapies healthcare payers may insist on someone failing on a cheaper drug before they can access a more expensive one; the emergence of biosimilars should bring the costs of injectables even lower and will entrench this requirement in some markets. Thirdly, if we can confirm and validate predictive response markers the injectables will be here for ever. For example, if I can say that the chances of you being rendered NEDA (no evident disease activity) with a normal brain atrophy rate is greater than 80% on interferon-beta, would you choose that compared to an oral without any validated response marker? Finally, if a black swan moment occurs and we find a viral cause of MS and are able to monitor the viral load, interferon-beta may be the platform therapy on to which we graft on other antivirals; an analogy being hepatitis C. Some people laugh when I talk about finding a viral aetiology, but there are many observations in MS that seriously question the autoimmune hypothesis or dogma. I covered a few of  these observations in my recent talk in Canada."

Why i think ms is an infectious disease for the blog from Gavin Giovannoni

Epub: Voloshyna et al. Natalizumab improves ambulation in relapsing-remitting multiple sclerosis: results from the prospective TIMER study and a retrospective analysis of AFFIRM.Eur J Neurol. 2014 Dec . doi: 10.1111/ene.12618.

BACKGROUND AND PURPOSE: Impaired ambulation is a prominent disabling symptom of multiple sclerosis and can lead to reduced quality of life. Whether natalizumab, a monoclonal antibody shown to reduce disease activity in relapsing-remitting multiple sclerosis, could impact ambulation performance was examined. 

METHODS: A prospective open-label study, TIMER, was conducted in natalizumab-naive MSers (n = 215). The timed 25-foot walk (T25FW) and timed 100-m walk (T100MW) were assessed at baseline and at weeks 24 and 48 of natalizumab therapy, together with Expanded Disability Status Scale scores. The effects of natalizumab on T25FW performance were also examined in a retrospective analysis of natalizumab-treated MSers (n = 627) and placebo control MSers (n = 315) from the AFFIRM study.

RESULTS: In TIMER, a significant increase from baseline in T25FW speed was seen at week 24 (P = 0.0074) and in T100MW speed at weeks 24 and 48 (both P < 0.001). A greater proportion of MSers showed clinically meaningful increases (≥20%) in walking speed on the T100MW (25%) than on the T25FW (13%) at week 48 (P = 0.032). In AFFIRM, natalizumab increased the proportion of patients with ≥20% confirmed improvement in T25FW speed at year 2 by 78% versus placebo (P = 0.0133).

CONCLUSIONS: Natalizumab increased walking speed in MSers with relapsing-remitting multiple sclerosis. The T100MW may be more sensitive to changes in ambulation capacity than the T25FW, and both tests appear to detect clinically meaningful improvements in ambulatory function.

CoI: multiple

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