“Although the upcoming approval of new drugs against multiple sclerosis will offer a number of additional treatment options, it is important that we keep one thing in mind: The only way we can get this disease well under control is if we manage to provide personalised therapy tailored to the individual and to predict the effects and side-effects of a given drug. Unfortunately these efforts are still in the early stages of development,” Prof Xavier Montalban (Multiple Sclerosis Centre of Catalonia, Spain) explained at the 23rd Meeting of the European Neurological Society (ENS) in Barcelona. More than 3,000 experts are currently gathered there to discuss latest developments in their field.
Prof Montalban urged that more pharmacologic research be done on biomarkers and that physicians cooperate more closely with patients to optimise therapy. Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterised by a high degree of heterogeneity. The clinical course of the disease and its degree of severity can vary widely from one individual to the next. It is now known that one and the same treatment can yield very different therapeutic results. Prof Montalban: “Despite an awareness of this problem, personalised therapy was not an issue for a long time, not least because of the lack of options. This situation could well change in the near future.”
Highly effective drugs but a host of risks
We are seeing the end of a “one drug fits all” approach to multiple sclerosis therapy, said Prof Montalban. “Myriad new treatment options are becoming established right now. There is a well-founded hope that we will be able to help people suffering from MS more effectively and more quickly in future. We were familiar with this disease for 120 years without being able to treat it. For 15 years, drugs have been available without noteworthy side-effects but limited in their effectiveness. In the meantime a number of highly effective drugs have been put on the market. However, they involve risks ranging from hair loss and bradycardia to progressive multifocal leukoencephalopathy (PML). PML is a dangerous viral infection caused by the immune-suppressive effect of some drugs and can have fatal consequences. Prof Montalban: “In the meantime a test has been developed for determining the probability of patients to develop PML. This is a welcome step in the right direction. The genetic causes of the varying effectiveness of individual types of drugs are becoming increasingly clear.” Interferon ?, the first disease-modifying drug that was approved, is effective on 20 to 55% of patients depending on the criteria applied. This fact has led science to make great efforts to find biomarkers that reliably indicate successful treatment and side-effects. Prof Montalban: “Right now we are at 100 possible biomarkers without a clear tendency. This shows how complex MS research is and how far we still have to go to achieve personalised medicine.”
Danger of changing or stopping therapy
Under certain circumstances, more pharmacogenetic findings could enable experts to predict the consequences of switching therapies. The medical field remains in the dark on many aspects of this issue too, to the detriment of those affected. A Catalonian study presented at the ENS Meeting shows how problematic it can be to switch therapies. After five years suffering from MS, the seven study participants were medicated with the highly effective disease-modifying drug natalizumab because the previous treatment had failed. Their state of health remained stable for the average period of about 2.5 years they took this substance. They then had to switch to other weaker drugs for reasons varying from PML risk to pregnancy and allergic reactions. Despite the alternative medication, the patients’ neurological state deteriorated quickly. After about three months, four of the seven subjects exhibited new lesions and two of the seven were even found to have sustained 40 new injuries to the central nervous system. A mere eleven months later, all patients had 40 to 70 new lesions. Prof Montalban: “When patients stop taking drugs like natalizumab, they can suffer disastrous relapses with a more aggressive disease than before. It is therefore urgent that we devise strategies to ensure greater continuity. This task extends beyond pharmacogenetics and requires a holistic approach to treatment.”
New treatment guidelines take individual factors into account
Evidence-based treatment guidelines on MS therapy are now being thoroughly updated in a project under Prof Montalban’s aegis and with the support of numerous national societies in this field. This revision takes account not only of the many pharmacological innovations such as oral therapies or drugs based on monoclonal antibodies. It also puts special emphasis on the many individual factors that personalise a therapy and make it more successful. These factors include thoroughly advising and informing the patients before treatment begins so they can decide on a therapy option and take part in carrying it out. To this end, the new guidelines also provide informational material for patients. Prof Montalban: “Initially, very fundamental questions have to be clarified: What do patients consider a successful therapy to be? What would they rather accept in this therapeutic tightrope walk: severe side-effects or early disablement? Are women planning to have children?” The decisive factor after that is to monitor and if need be, adapt the successful therapy. Prof Montalban: “To be successful, each therapy decision must be made in close consultation with the patients. Today, a patient-centred approach is more possible than ever before. That is because MS breaks out mostly in young adults aged 20 to 40. As a general rule, this group is digitally competent and can use the Internet to keep in constant contact with the physicians treating them. The extensive involvement of the patients is especially important with MS to increase compliance.” Prof Montalban hopes the new guidelines will be implemented quickly and create greater awareness for personalised therapy options amongst general practitioners and neurologists.
23rd Meeting of the European Society of Neurology (ENS) 2013.
ENS Abstract P 710: Development of a clinical practice guideline on the management of multiple sclerosis using the GRADE methodological approach;
ENS Abstract 169: Personalised treatment of Multiple Sclerosis: Safety;
ENS Abstract 171: Personalised treatment of Multiple Sclerosis: Shared decision-making and patient-centred care;
ENS Abstract O231: Catastrophic multiple sclerosis rebound after natalizumab treatment discontinuation;
Comabella, Manuel/Montalban, Xavier (2012): “Multiple sclerosis and immunological response: time for a personalised therapy?” in: Hot Topics in Neurology and Psychiatry 2012; 13, pp.19-25
European Neurological Society