Why didn't Pharma commercialise an interferon response marker? They will pay for it. #MSBlog #MSResearch #ClinicSpeak
"The study below confirms what has been established by several other groups that if you have a signature in your blood that your own immune system is churning out interferon you are unlikely to be a responder to interferon-beta treatment. You are probably aware that interferon-beta is a natural anti-viral cytokine that is produced as part of the inflammatory reaction. Interferon binds to receptors on cells and stimulates cells to make anti-viral proteins. One anti-viral protein that is specific for interferon-beta is myxovirus resistance protein A or MxA. If your MxA levels are high in your blood it indicates that your body is producing your own interferon-beta. In the study below MSers with a high baseline level of MxA, i.e. before starting treatment with interferon-beta, were more likely to be non-responders to treatment. In comparison, those MSers without raised MxA levels were more likely to respond to treatment. Unfortunately when the researchers ran a so called receiver-operating curve, or ROC, analysis the test did not quite cut the muster as being useful clinically. In general, for a test to be clinically useful it has to have a sensitivity and specificity of greater than 80%; however, there are exceptions to the rule."
"I an convinced by this data as this finding has been confirmed by several other groups. I only wish the Pharma companies had validated this data as part of their phase 4 programmes so that we could use this test in clinical practice. A test like this is what we need to select MSers who are more likely to respond to a treatment than not. However, things have now moved on an most MSer when given a choice between an injectable DMT such as interferon-beta or an oral (teriflunomide or DMF) go for the latter. Please note in the UK we can't offer fingolimod 1st-line, unlike in many other countries."
"One of the problems with selecting a 1st-line therapy that only a minority of MSers will respond to (<50%), such as interferon-beta, is that the majority (>60%) will need to be monitored and switched to another therapy under our treat-2-target of NEDA strategy. Depending on your monitoring frequency, and whether or not you use MRI activity to guide treatment, it can take 1, 2, 3 or even 4 years to classify a MSer as a non-responder to interferon-beta. During this time MS can cause a lot of irreversible damage. So at a population level using moderately effective therapies 1st-line disadvantages the majority with and advantage of finding a safe treatment for the minority or responders. In comparison, using a highly-effective 1st-line treatment strategy benefits the majority at a cost of safety issues for a minority of MSers. If I was a population health doctor it would be no-brainer; I would go for the latter option; let the majority benefit at the cost of the minority. The latter is what underpins population vaccine programmes. This is probably why New Zealand have stopped their neurologists prescribing interferon-beta and GA as first-line therapies; they are now limiting the 1st-line treatment options to fingolimod and natalizumab. The New Zealanders have clearly seen the light and over the next 10 years you will see New Zealand MSers shoot-up the national league tables in terms of MS outcomes. I hope NICE and NHS England are watching this space."
BACKGROUND: Myxovirus resistance protein A (MxA) is a molecule induced after interferon-beta injection, mostly used to evaluate its bioactivity. There is little available data on clinical utility of baseline MxA mRNA status. The objective of the study is to investigate whether baseline MxA mRNA expression can predict relapse and disease progression in multiple sclerosis patients treated with interferon-beta.
METHODS: Baseline blood samples were obtained before the first interferon-beta dose was administered to evaluate MxA mRNA expression using real-time polymerase chain reaction (PCR). Demographic and clinical variables were prospectively recorded to define treatment responder and non responder groups.
RESULTS:104 patients were included in the study. Baseline MxA mRNA expression was significantly lower in the group of patients who met the definition of responders (1.07 vs 1.95, Student t test, p<0.0001). A threshold of 1.096 was established using Receiver Operating Characteristic analysis to differentiate between responders and non-responders (sensitivity 73.9%, specificity 69.0%). Survival analysis using this threshold showed that time to next relapse (p<0.0001) and to EDSS progression (p = 0.01) were significantly higher in patients with lower MxA titers.
CONCLUSION: The results suggest that baseline MxA mRNA levels may be useful for predicting whether multiple sclerosis patients will respond or not to interferon-beta treatment.