Researchers referenced in this news release presented study findings last week at a national multiple sclerosis (MS) meeting suggesting that giving the drug natalizumab less frequently may dramatically reduce the risk for developing progressive multifocal leukoencephalopathy (PML), a rare but potentially fatal brain infection.
The news release describes the study design well but could have served readers better by including more about costs, harms, significant conflicts of interest, and some important limitations of the study.
Although there is no cure for multiple sclerosis there are a variety of treatments available that target the symptoms and progression of the disease. Most of these carry significant side effects and are closely followed by people with MS. An unpublished study such as this — which investigates one of the more feared side effects — is likely to generate a great deal of interest. This places a premium on being appropriately cautious in writing a news release about a study that has not been published and raises questions regarding conflicts of interest.
The cost of infusing natalizumab is not mentioned, but this study found the 2-year cost to be $72,120.
The news release mentions the main benefit of less frequent dosing of natalizumab (infusions every five to 12 weeks, instead of the standard every 4 weeks) as a “risk reduction for PML as high as 94 percent” up to 6 years. The news release mentions “the optimal extended dose schedule is not known.”
What we like news releases and news articles to provide readers are absolute risk reductions, rather than the relative risk reductions provided here.
The news release does make it clear that these results only apply to patients who test positive for antibodies to the JC Virus (JCV; the virus that causes PML) and this study did not look at drug efficacy comparing the extended to standard monthly dosing.
Other than progressive multifocal leukoencephalopathy (PML) — the side effect targeted in this study — the other side effects of natalizumab therapy are not mentioned. The most serious include liver toxicity, and infections from immunosuppression.
Furthermore, although many other therapies which cause immunosuppression can lead to PML, it might have been helpful for readers to know that natalizumab has proven particularly worrisome in this regard. It’s been pulled from the market in the past because of PML concerns, and it’s recommended by many in the MS field to be used in very limited circumstances.
Although the news release does mention these results were presented at a meeting on February 2, 2018, it would help to clarify whether these results have been published yet in a peer-reviewed journal. Besides being an unpublished abstract, this was an observational study, not a clinical trial.
A major limitation of this study — not mentioned in the news release — is the inability to control for baseline disease characteristics which might affect the risk for developing PML. This limitation is common to all observational studies, which are unable to demonstrate cause-and-effect, and it’s the reason that descriptions of such studies should avoid cause-and-effect language like we find in the headline, “Extending dosing intervals reduces deadly side effect risk.”
There is no disease mongering here. Progressive multifocal leukoencephalopathy (PML) is a well-documented side effect in MS patients on long-term natalizumab therapy (as well as other treatments which cause immunosuppression). The news release mentions 756 reported PML cases worldwide as of January 2018 with a global incidence rate of about 4 per 1,000 PML cases in people treated with this monoclonal antibody therapy.
Although the news release does mention that natalizumab is manufactured by Biogen — and that Biogen “provided the researchers access to their data and statistical support” — it does not mention that the lead author receives research support from Biogen, as well as personal compensation from Biogen for speaker and advisory board activities.
It’s also not mentioned that half of the 14 coauthors listed for this study are employees of — and own stock and/or stock options — in Biogen.
There is no cure for multiple sclerosis. Most treatment options focus on managing symptoms or slowing progression of the disease. There are several other forms of treatment for MS other than natalizumab. Two of these alternatives (alemtuzumab and ocrelizumab) are mentioned at the very end of the news release.
The news release does mention that natalizumab is a ‘commonly-prescribed multiple sclerosis (MS) infusion medication linked to a rare but serious side effect … ”
It should have been made more clear, however, that the drug has been pulled from the market before (over PML concerns) and is now FDA-approved only for highly active, relapsing remitting MS.
There have been other studies looking at the role of extended-interval dosing (EID) with natalizumab, but the news release does not make it clear if this study is unique in using registry data to explore the relationship between EID and the subsequent development of PML.
The news release goes over-the-top in claiming that this preliminary study (whose data are not even released in a peer-reviewed journal) is “practice changing and may save lives.”