Clinic speak: should I listen to my neurologist?

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

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