Switching decisions

For many people with relapsing remitting MS, the injectable medications such as the interferon-betas or glatiramer acetate can provide good control of relapses. However, others continue to experience relapses and clinicians may recommend switching, or ‘escalating’ to another form of therapy, such as natalizumab (Tysabri) or fingolimod (Gilenya). However, there have been no clinical trials conducted to directly compare the outcomes of switching to either of these agents.

In the absence of a clinical trial Dr Tomas Kalincik and collaborators in the MSBase consortium have published an analysis on the outcomes of treatment choices when switching from injectable medications to fingolimod or natalizumab. Data was examined using the powerful MSBase database. Dr Kalincik was previously supported by a MS Research Australia Postdoctoral Fellowship that ended in 2013.

The MSBase registry is the largest international MS registry for recording clinical outcomes, and contains clinical data from over 33,000 patients including many from Australia. It is an invaluable resource for answering questions that are difficult to assess using traditional clinical trial methodology. Dr Kalincik has been using this data to investigate questions of long-term outcomes of treatment decisions in groups of patients with different sets of characteristics.

Patients within the database can be matched on a range of different factors, such as age, sex and disease duration and grouped to essentially construct retrospective or ‘virtual’ clinical trials, using ‘real-life’ data collected in routine clinical practice.

In this study, published in the journal Annals of Neurology, Dr Kalincik and the team examined the data from 578 matched people with MS who had experienced active disease despite being on an injectable form of medication. 407 were switched to natalizumab, and 171 were switched to fingolimod. An average of 12 months of clinical data was available on each patient following the switch.

The data revealed that the annualised relapse rate dropped from 1.5 to 0.2 for those who were switched to natalizumab and from 1.3 to 0.4 for those switched to fingolimod. There was no statistically significant difference in overall disability progression between the two groups of patients, however of those switching to natalizumab there was a greater probability of experiencing a reduction of disability level that persisted for 6 months or more.

This data indicates that both natalizumab and fingolimod showed significant and substantial reductions in the overall relapse rate following treatment switching, with greater reductions in relapses following a switch to natalizumab. However, the authors also note that a main limitation of the study was the follow-up duration, as less than 10% of the patients had been followed for 2 years or more following the switch. The team intend to examine the long-term disability outcomes in future years once the number of patients on these medications and length of follow-up time in the MSBase database increases.

The efficacy of different medications in reducing relapses and disability is just one of several factors that should be taken into consideration when people with MS and their neurologists consider treatment options. Other factors such as disease severity, treatment risks, side-effects and other health conditions all form part of the overall picture in arriving at a treatment choice that is best suited to each individual’s circumstances.

This is why Dr Kalincik’s work is so vital in providing a full picture of the advantages and disadvantages of medications, based not only on the results from formal clinical trials, but also the ‘real-life’ data from the use of medications in the normal clinical setting. During his MS Research Australia-funded Fellowship, Dr Kalincik has conducted many analyses of the powerful MSBase data, with the ultimate goal of creating an online ‘risk calculator’ that will assist patients and clinicians to use all information available to them, to help understand their prognosis and select the most effective treatment for their circumstances.

Dr Kalinicik and his colleagues also recently used this same data to examine the long-term outcomes for patients on the different forms of injectable medications view article here.