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I have MS and I got Avonex treatment. I want to know about one thing, is there an obligation to get Avonex once or twice a week? If we do it, for example, once a month, what can happen? Answer: There was an initial reason for dosing Avonex injections once a week that was established prior to the pivotal clinical trial started over 30 years ago. Pre-clinical studies showed that downstream activation of interferon sensitive genes (ISGs) after injection of Avonex 30 ug in normal controls, and subsequently people with MS, led to secretion of certain proteins (MxA and neopterin) easy to measure in a blood test that persisted for up to 5 days. This information was used to select a dosing interval of once a week. It is important to note that there is no clinical evidence that secretion of MxA or neopterin after Type 1 interferon injections (e.g. avonex, betaseron or rebif) is at all responsible for any benefits of this therapy; this was simply an easy to measure marker of activation of ISGs. The phase III clinical trial of Avonex demonstrated the known benefits of Avonex with once weekly dosing and the rest is history. Since the original approval of Type 1 interferons to treat relapsing forms of MS, there has been continued debate about the effects of different doses and dose intervals of all Type 1 interferons. If all patients with a diagnosis of MS exhibited similar dysregulation of type I interferon responsiveness, then it is likely that higher doses would benefit people with MS not responding to standard dosing. However, Richard Ransohoff and Tony Reder, two prominent experts on interferon signaling, demonstrated years ago that approximately 20 % of relapsing MS patients exhibit an overactive response to Type I interferon injections that is associated with continued disease activity or even an increase in pre-treatment MS disease activity on standard dosing. This overactive response to Type I interferon signaling is similar to what we observe in patients with lupus (SLE) and neuromyelitis optica (NMO), two conditions known to worsen when treated with Type I interferons. Therefore, it would not make sense to increase the dose or dose frequency of type 1 interferons in relapsing MS patients experiencing breakthrough disease on these therapies unless there was a validated method to predictably determine their interferon responsiveness. Of course, one could argue for increasing doses or dose intervals of interferons if there was controlled clinical trial evidence that this strategy was effective. Unfortunately, this type of study was never done and would not be considered ethical in the current environment of readily available, highly active, well tolerated disease modifying therapies with treatment effects far larger than those observed with interferons. However, this study would be ethical if you could reliably exclude those MS patients with an overactive response to Type I interferon signaling. Great question. Revere P (Rip) Kinkel, MDProfessor of Neurosciences Director of the Multiple Sclerosis Program University of California San Diego #Avonex #multiplesclerosis #MS
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