Everyone with real insight into XLH, like patients, caregivers, and expert clinicians who have seen more than a handful of us, has known for years that burosumab is a huge improvement over the old phosphorus/calcitriol treatment. But there are still too many people in health care who don’t accept that conclusion yet, so it’s useful to have a new article on the subject, “Real-World Effectiveness of Burosumab Versus Oral Phosphate and Active Vitamin D in Adults With XLH,” which gives us an additional journal article to provide to the skeptics.
This article is based on the first year of data collected from the limited natural history study established by Ultragenyx in the wake of the approval of burosumab by the U.S. FDA. For the purposes of this article, only 139 patients’ data was reviewed (out of a larger number enrolled), since they excluded those patients who had received burosumab treatment previously (i.e., who were in the clinical trial). This way, they could see the trajectory of two groups of patients — those who began burosumab over the course of the year, and those who remained on phosphorus/calcitriol treatment. Then they did a bunch of math that’s way beyond my expertise, and concluded, “To the best of our knowledge, the current study is the first comparative study of burosumab versus [phos/calcitriol] in adults with XLH, and results showed that burosumab treatment was associated with significant improvements in [lab results], [patient reported outcomes like pain and fatigue], and mobility, compared with [phos/calcitriol].”
This is extremely useful information for any battles over the appropriateness/necessity of burosumab treatment, so I encourage you to read the article and eventually print it out to have on hand in case a clinician or insurer questions the value of burosumab. (Note that it’s in an unofficial PDF form at the moment, so you may want to wait another month or two to print out the official version. I’ll try to remember to remind you!)
A couple of caveats: First, I still loathe the term, Disease Monitoring Project, which I believe is used exclusively by Ultragenyx-sponsored research (or what started out as Ultragenyx-sponsored and may have been inherited by Kyowa Kirin). It annoys me because it rejects a perfectly functional term that’s well-recognized (natural history study) and replaces it with something that has to be defined, because no one knows what the heck it is, and the definition is … not patient-friendly. A DMP, as defined in this article, is a “a prospective, multicenter, longitudinal, … observational outcomes program.” In other words, it’s a natural history study, with is generally referred to as a prospective, longitudinal, observational (as opposed to interventional) study, and they’re often multi-center, because they require significant numbers of patients enrolled, in order to have useful data. Sigh. But that’s just the word-nerd in me, and the research itself and the article are both useful enough to justify overlooking the annoying language.
Second, and more substantively, it’s important to note that this is just one year’s worth of data being analyzed, and most of the skepticism surrounding burosumab has to do with long-term treatment. Most clinicians (and even insurers, I suspect) will acknowledge that the first year of burosumab treatment offers significant value, but they get twitchy if you suggest that patients should be on this treatment for the rest of our lives. This article won’t help with that long-term benefit issue, and the authors acknowledge, “Additional studies are required to determine if the results of this analysis are sustained over an extended follow-up period.” I would expect that there will be future articles showing the ongoing benefits at the five-year mark and eventually the ten-year mark. The study started in the summer/fall of 2018, so it had already collected five years worth of data as of late 2023. It can take a year or two for the process of writing, submitting, reviewing, and editing to play out, before the analysis shows up in journals, so I’m hopeful that we’ll see it in the next year or so. We won’t convert the skeptics entirely until we have the ten-year data in 2028 (published in 2030 or thereabouts), but the five-year data will be a good step forward.
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Please note that the author is a well-read patient, not a doctor, and is not offering medical or legal advice.
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