Clinic speak: should I listen to my neurologist?

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Should you question your neurologist’s advice? #MSBlog #MSResearch #ClinicSpeak


Question: “Prof G I live in the US and have recently been diagnosed with MS having had two attacks in just over a year. Fortunately I have made a full recovery and I am currently well. My neurologist has recommended I start on either Tecfidera, Gilenya or Tysabri if I am negative for the JC virus. He feels the market for the injectables are dead as they are not that effective. He believes the newer generation drugs are better at preventing problems from MS in the future. What would you advise?”

“I only wish the answer to treating MS was that simple. All he is doing is recommending higher efficacy drugs in the hope you will do better on them than interferon-beta (IFNb) or glatiramer acetate (GA). Statistically he is correct, but he doesn’t really know if you will be a responder or non-responder to IFNb or GA. The only way to find out is to put you on these drugs and see how you do. If you continue to have clinical or sub-clinical disease activity (MRI-only) he could then escalate your treatment. In the UK we don’t have these options available to us. Although BG12 (Tecfidera) has been given the green light by the EMA, Biogen-Idec are in dispute with the EU regarding the length of BG12’s patent. Therefore we are not sure if BG12 will be launched in the EU or not. Fingolimod, on the other hand can only be used in MSers who failed IFNb. The following are our NICE guidelines for prescribing fingolimod: fingolimod is recommended as an option for the treatment of highly active relapsing–remitting multiple sclerosis in adults, only if: they have an unchanged or increased relapse rate or on-going severe relapses compared with the previous year despite treatment with beta interferon. In comparison, natalizumab can only be used as a first-line therapy in MSers with rapidly evolving severe relapsing–remitting multiple sclerosis (RES). RES is defined by two or more disabling relapses in 1 year, and one or more gadolinium-enhancing lesions on brain magnetic resonance imaging (MRI) or a significant increase in T2 lesion load compared with a previous MRI. Based on these criteria I would only have the option of offering you IFNb or GA, or the option of participating in a clinical trial. The NHS are actively encouraging the latter; new guidance states that it is our duty to inform patients of the possibility of participating in clinical trials if any trials are available.”

“The other option you may not have considered is no treatment or watchful waiting. Very recently a patient of mine with highly-active disease chose this option despite me recommending treatment. She is highly-educated and knows exactly what she is doing. She was not keen on the risk of PML from natalizumab as she was JCV seropositive and did not want the hassle of injecting herself. She wants to try lifestyle treatments and high-dose vitamin D first. If her disease remains active over the next 6-12 months she will reconsider her options. She is also aware that other treatments may become available to her in the near future. I also offered her the option of participating in one of three clinical trials we were recruiting for at the time and she said no. C’est la vie! Despite my reservations I respect her decision and will look after her as I do any other of my patients. It is all about informed decisions and choice.”

“Coming back to your neurologists opinion about the market for injectables being dead. He may be correct in established markets such as the US. However, in emerging markets that are cost-sensitive, cheaper biosimilar or generic formulations of IFNb and GA will remain first-line options for many years. In addition, a test that predicts response to these drugs may become available that will allow us to predict who will be a responder and non-responder. Several promising markers already exist in relation to the IFNb preparations, but have never been validated for use in clinical practice. In general neurologists are quite conservative and are comfortable with the benefit:risk profile of IFNb and GA and will therefore continue to prescribe these drugs for many years.”


“If I had MS and was stable with no evidence of disease activity (NEDA) on IFNb or GA why would I take a chance of one of the newer drugs when there is no guarantee that I would be a responder or non-responder? So there is plenty of life left in IFNb and GA; particularly in the UK.”


“Although I am a strong proponent of having the choice of early highly-effective treatments and adopting a zero-tolerance strategy to MS disease activity by treating-2-target of NEDA my hands are tied by UK treatment guidelines. NICE for example does not allow us to escalate treatment with subclinical or MRI evidence of disease activity  In fact most neurologists in Europe are in a similar position to us. You should therefore consider yourself very fortunate to have the option of choosing with your neurologist different treatment strategies; this is what personalised medicine is all about. As always the US are pioneers, early adopters and leaders in the field of personalised medicine.”

CoI: multiple

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

16 comments

  • I'm in the US, and I very much appreciate that you said this:

    "If I had MS and was stable with no evidence of disease activity (NEDA) on IFNb or GA why would I take a chance of one of the newer drugs when there is no guarantee that I would be a responder or non-responder? So there is plenty of life left in IFNb and GA."

    I read this blog all the time, and I constantly question whether I ought to stay on my GA. I've been on it since my diagnosis 2 years ago. I get an annual MRI and am so far NEDA. But then I read about the stronger drugs and wonder if I wouldn't like a little reversal of symptoms from one of the -mabs. Or the better insurance that a nasty life-changing relapse isn't waiting for me tomorrow. It's a difficult call. It's very helpful to know what someone who has seen MS for years thinks.

    • I have had MS for nearly 13 yrs now. Delayed DX so missed the boat on getting join tax. I also chose the monitor and see approach, as anyways I had no real other option. I have been taking vit D since 2008. Averaging around 6,00o-8,000 IUs per day. My levels hover around 110, although will aim for at least 120. No clinical relapses for at least 6 yes, even that was sensory. MRIs have not shown activity also for past few years, and no evidence of atrophy. Most of my complaints are fatigue, pain, and some cognitive, and apathy actually. But these are not new.

      Just sharing this cuz it's hard to say whether the vit d is helping, or (likely) I have a milker form of MS. Mild being a relative term of course. The call as to what course to take is yours, in conjunction with your neuro. The clinical spectrum oif MS is vast, and there are no guarantees. Just make sure whatever you decide, you do not regret it later. I don't, even if I go downhill later.

  • "If I had MS and was stable with no evidence of disease activity (NEDA) on IFNb or GA why would I take a chance of one of the newer drugs when there is no guarantee that I would be a responder or non-responder? So there is plenty of life left in IFNb and GA."

    Would you ignore the fact that INFb or GA won't prevent SPMS and won't prevent you ending in WC?

    • Re: "Would you ignore the fact that INFb or GA won't prevent SPMS and won't prevent you ending in WC?"

      This refers to the average effect of the drug and does not necessarily apply to the individual. We know that earlier access IFNbeta delays you getting to all disability stages including EDSS 10.0 or death. I suspect that if you are NEDA you have a much greater chance of have a more favourable course and possibly avoiding these poor outcomes. Unfortunately, we don't have long-term data on the benefits or being rendered NEDA positive. We do know that in short-term studies you do much better.

    • "Would you ignore the fact that INFb or GA won't prevent SPMS and won't prevent you ending in WC?"

      Where do you get this B.S.? After 15 years of continuous use of GA, only 2/3 of msers transitioned to SPMS and 57% had stable or improved EDSS scores:

      http://msj.sagepub.com/content/16/3/342.full.pdf

      Yes they may be super responders to GA, but just because it does not work for you does not mean it does not work. The key is to treat early, but my guess is that you are one of the "wait and see" geniuses that found out these drugs don't work on progressive MS.

    • The problem with the open label extension studies is that they are enriched for responders. Non-responders drop out. So we can't extrapolate these results to everyone. But I do agree there are a subset of MSers who do very well on GA and become NEDA positive and do very well in the long-term and seem to avoid SPMS. What will happen to them after 20, 30 and 40 years is unknown.

    • The way I look at GA is analogous to allergy shots. If you have an allergy to something (lets say a cat) you can get shots containing small amounts of cat protien. Over time you eventually become tolerant of cats. Likewise, GA contains proteins that mimic the myelin sheath and exposure to this over the long term induces tolerance.

      I realize this is a simplistic explanation of how GA might work but it makes sense to me. And I don't think anyone would take alergy shots for an acute alergy attack, just like GA is probably not the best drug for the quickest shut-down of disease activity.

      Hopefully I am a responder to GA, but if not I may try induction therapy to halt activity and switch back (or preferebly stay on) to GA for the long term.

    • Maybe as good as any suggestion such as T reg, CD8 suppressors etc. etc.

      As GA contains 4 of the 20 amino acids I wonder if it works on any other immune condition

  • "As always the US are pioneers, early adopters and leaders in the field of personalised medicine."

    I'm not sure whether people without medical insurance have access to this treatment… do you know?

    • The uninsured don't necessarily have access to these drugs. As always money buys you access to care and the difference between the haves and have-nots is appalling.

    • While there is a big difference in available health care in the US (although that is quickly changing), most pharma companies get the very expensive drugs to anybody who needs them from what I've seen–MS, cancer, or otherwise. My impression is that they are not really interested in wiping individuals out financially (nor do they want to be the company that withheld something from a sick kid), but they're very interested in your insurance company's bank account.

    • I know for me, my insurance company didn't want to cover Tecfidera so I went with the program Biogen offered. So far, it feels a world different than my experience with Avonex. But yes, I do see your point that those with money have a totally different experience when it comes to what they can access and get.

  • How do we go about getting NICE to change it's guidance to allow escalation to more effective DMTs direct from GA too rather than just IFN i.e. what can we do to 'close the doughnut'?

  • Please NHS start with annual MRI, so we know our NEDA status – with or without access to the newer highly effective drugs…

By Prof G

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