Do interferons work?
A new Canadian study is generating significant controversy in the multiple sclerosis (MS) world with its finding that injectable interferon-beta medications do not appear to lower the risk of developing disability (Shirani and colleagues. JAMA 2012;308:247-256). [Tune in to MS Radio to hear an interview with researcher Helen Tremlett).
The retrospective study collected data on over 2,600 people in the BC MS database, which has information on about 80% of people with MS in the province. The analysis looked at how well people did if they were treated with an interferon during the 10-year period after drug approval (1995-2004), and compared these results with two control groups – those who did not start treatment during that same period (1995-2004), and those from an historical group with MS (1985-1995). For the purposes of the analysis, all interferon drugs (Avonex, Betaseron, the two doses of Rebif) were considered to be the same. About 93% of people taking an interferon had only a short break (less than 3 months) when they switched from one interferon to another.
The main objective of the study was to determine if there was a difference in the proportion of people who reached EDSS 6 (i.e. requiring a cane or other walking aid to walk 100 meters).
At the end of the observation period, 10.8% taking an interferon had reached EDSS 6, compared to 5.3% who did not take an interferon and 23.1% of the historical controls. There was no statistical difference between the interferon group and either of the two control groups.
The conclusion was that interferons do not reduce the progression of disability in people with relapsing-remitting MS. A limitation of the study is that people in the untreated group may have been less ill, so they may have been less likely to have disability progression.
Other studies have reported conflicting results. An Italian study reported that interferons reduce the risk of disability (Trojano and colleagues. Ann Neurol 2009;66:513-520). However, these findings were later questioned (Renoux & Suissa. Ann Neurol 2008;64:109-110; Koch and colleagues. Ann Neurol 2008;63:125-127). In fact, two systematic reviews of MS studies concluded that interferons had a modest effect at best on disability (Rice and colleagues. Cochrane Database Syst Rev 2001;(4):CD002002), and that the benefit of treatment was uncertain after the first year (Filippini and colleagues. Lancet 2003;361:545-552).
A further concern is that two recent studies of people with “pre-MS” (called clinically isolated syndrome, or CIS) found that starting interferon treatment earlier had no additional benefit on the risk of developing disability five or 10 years later (Kappos and colleagues. Lancet Neurol 2009;8:987-997; Kinkel and colleagues. Arch Neurol 2012;69:183-190). This raised questions about the benefits of the “stitch in time” approach to treating MS.
The broader question is whether drugs that reduce the inflammation seen in MS (which results in symptoms, relapses and MRI findings) are effective in controlling the neurodegenerative component of the disease (which results in disability progression). Reducing relapses is welcome, but what worries most people with MS is disability progression: Will I need a cane? Will I need a wheelchair? It isn’t clear if interferons will help in the area that really matters.
While the UBC study raises some serious questions about the benefits of interferons in MS, it’s best not to jump to any conclusions. The current crop of injectable medications may provide some advantage in the short term (such as in the first couple of years after diagnosis), or may benefit other areas (such as cognition). A great deal is still unknown.
If you have concerns about the medication you’re taking, don’t stop it on your own. Explore your options and talk to your neurologist about the best medication for your specific circumstances.
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