A blood test is now being used as a form of monitoring drug therapy progress, and has shown to be very effective so far.
The new blood test
A blood test has been developed to keep track of how the treatment effect of drugs in multiple sclerosis, and so far it is showing positive results. Recent information has depicted that it correlates with MS lesions, brain volume loss, number of relapses, and disability progression.
The test is intended to measure the blood levels of neuronal structural proteins that are specifically known as neurofilament lights chains, or NfLs. Before the test, some implied that blood levels of NfLs could prove to be an important biomarker of neuroaxonal loss in multiple sclerosis, and now the study is able to show how these blood NfL levels correlate with the markers of disease progression.
Maria Pia Sormani, PhD, of the University of Genoa in Italy, commented on the team's work: "Our study has the novelty of comparing patients treated with placebo to patients treated with an active drug in a randomized context, showing that NfL in the blood is able to detect a treatment effect. This is very important to validate NfL as a measure sensitive to monitor the efficacy of drugs in MS. Our results show that NfL can be used as an endpoint to assess treatment effects on both inflammatory and degenerative aspects of MS in clinical trials."
Unveiling the study
The researchers presented the findings from their study at the 7th Join European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2017.
Dr. Sormani and her colleagues showed how they used blood samples from the FREEDOMS study to analyze. These were with fingolimod in relapsing-remitting MS, and unveiled how NfL levels are connected to other ways in which multiple sclerosis progresses, such as T2 lesion formation, brain volume loss, relapse activity, and disability progression.
Looking at NfL
To conduct their study, the researchers took the data from patients that were enrolled in the FREEDOMS study, and with their consent, they analyzed the biomarker, followed by an NfL assessment after six months.
The study showed that the blood NfL levels at the beginning of the test were comparable between two of the groups analyzed - 26 pg/mL were the median levels for those in the placebo group, and 28 pg/mL were that of the fingolimod group. However, after six months of treatment, those same levels were shown to be drastically lower in the fingolimod group, while they did not change significantly in the placebo group.
At the 6 month mark, NfL was found to be correlated to measures of disease activity and severity at 24 months. This involves a variety of aspects, including how many T2 lesions were present, how many relapses had occurred, the levels of brain volume loss, and 6 month confirmed disability progression.
So, how did the treatment impact those involved? The percentage treatment effect on the two year mark relapses explained on NfL levels at 6 months was shown to be around 30 percent, which is precisely the same as that which can be explained by the impact on the number of T2 lesions at six months.
On the other hand, the percentage treatment effect at the two year mark brain volume loss explained by the effect on NfL at 6 months was 58 percent, which is drastically higher than the 39 percent explained by the number of T2 lesions at six months.
“A better predictor than brain MRI”
The researcher's results uncovered how fingolimod is capable of significantly decreasing the blood NfL levels, as compared to when a placebo was taken at 6 months. It was also found that 6-month NfL levels were correlated to standard measures of disease activity and severity, after being tracked for 2 years.
Their results also showed that blood NfL levels at six months offer a very similar effect as the fingolimod treatment in regard to how many relapses are experienced at the two year mark, as T2 lesions on MRI. These also correlated more strongly with how fingolimod treatment impacts brain volume loss at the two year mark.
Robert Fox, MD, of the Cleveland Clinic Foundation in Ohio took the time to comment on these results, and what they meant, at the ECTRIMS/ACTRIMS meeting. He said that it is "very encouraging news on NfL as a predictor of treatment responses. It appears to be a better predictor of what patients will do and the treatment response than typically used brain MRI."
Jeffrey Cohen, MD, who is also of Cleveland Clinic, commented as well, saying that NfL is a biomarker of particular interest in the field at the moment, especially in regard to how it pertains to multiple sclerosis disease activity and its ability to be measured in the blood. He says, "there is now a very consistent body of evidence showing that it reflects CNS [central nervous system] damage and predicts disability. This new study shows it reflects beneficial treatment effects of medication, and it is now starting to be used as a measure of drug effect in new clinical trials. I believe it will eventually also be used in the clinic to track disease activity."
Dr. Cohen went on to state that access to a simple blood marker of disease activity, like NfL, could be crucial in creating treatments that are more personal to each patient. He says, "right now we have a 'one size fits all' approach to treatment, but the goal is to tailor therapy so those patients with the most aggressive disease receive the most efficacious therapies early on. To do this, we need to regularly monitor disease activity, and having a blood test that reflects disease progression will enable this to be done much more easily."
Dr. Sormani also commented on how the implementation of NfL to monitor patients in a routine manner would likely be extremely effective, but that the approach simply is not at that point yet, and needs more research to be conducted before it can be done. She says, "standardization of the technique is a first requirement, to have reference values that can be interpreted by everyone ... I think it will be very useful in complementing MRI, but I don't think it will replace MRI, which gives a morphological and functional picture of the brain. Initially NfL will be used as a quick and easy screening tool to assess the activity of new drugs."
Sormani also commented on how much of an advantage NfL could be when used in retrospection. She says, "we have a large amount of clinical trial data that can be reanalyzed if blood samples have been properly stored. I hope pharma companies will do their best to reassess these precious data, from which we can get very relevant information about NfL levels and its relationship with other clinical variables."
Moving forward with the study
Going forward, the researchers want to proceed with their study. However, for a phase 2 study, between 60 to 130 patients will be needed when involving a drug with efficacy that is comparable to that of fingolimod versus a placebo at 90 percent power. Should they receive enough participants, they plan to conduct the study.