I’m starting to wonder when journals are going to stop publishing essentially the same article, over and over, on the topic of experts’ opinions about XLH treatment. I mean, it’s good to have consensus (especially when it mostly agrees with what patients expect from treatment), but it also feels like a waste of time and resources to say the same thing over and over when there are still plenty of issues that patients need researched.
In any event, the newest article is by clinicians in Italy, “Experts’ consensus on the management and treatment of individuals with X-linked hypophosphatemia across lifespan.” It’s fundamentally solid, although it’s not my favorite article on the topic.
Weaknesses: it starts by referring to XLH as a “skeletal” disorder, when it’s important to add the “musculo-” aspect too. (Although, I should note that in a chart summarizing symptoms, they do include the “musculo” element. I just would have liked to see it in the introduction, since more people will see the first few sentences than will see the charts.) Too often, there’s an assumption that if the bones can be made straight and strong, potentially with surgery instead of pharmacological treatment, or for a given point in time without regard for maintenance, the patient will have no further symptoms, and we know that’s false.
I also don’t like the use of GRADE, structure for making opinions look more objective, when logically, they really aren’t objective; plus, it doesn’t have very strong incentives for listening to patients directly instead of filtered through clinicians who may or may not know what patients care about), but it seems to be growing in popularity.
Another issue I have with the article (although to be fair, it’s an almost-universal problem) is that it persists in calling the old, ineffective treatment “conventional,” which implies standard and effective, even as the authors are pointing out its risks and ineffectiveness. (If they’d consulted patients to review the article, they might have been guided to the use of better terminology, but there doesn’t seem to have been any significant patient-voice engagement.) In fact, they ultimately state “Conventional treatment should be considered only when burosumab cannot be administered.” Which seems inconsistent with it being “conventional.” It makes me wonder if at some point in history there was an article (or, more likely, a speech) referring to using leeches to cure anemia that said something like “Conventional (leech) treatment should be considered only when iron supplements cannot be administered.” The sentence contains such internal contradiction that reading it makes my brain want to explode.
We have got to stop referring to the old treatment as “conventional” or “standard” or anything other than “old, outdated, difficult to manage, marginally effective at best, with significant adverse side-effects.” I mean, the article points out that in the 1970s (and before then, in my experience), patients were treated with massive doses of vitamin D. At the time, it was standard of care, despite being terrible, so presumably, clinicians then called that treatment “conventional,” and yet, once science proved that it was worthless-to-harmful, they stopped calling it “conventional.”
The article is also potentially confusing on one point, because despite pointing out all the reasons why adult treatment with phosphorus and calcitriol is problematic and ineffective, Statement 14 is: “Conventional treatment should be considered in symptomatic adults with XLH or who are planning orthopaedic or dental surgery, and during pregnancy/lactation.” That comes RIGHT AFTER saying burosumab is the preferred treatment, so it’s not clear if they’re suggesting that the old treatment is preferred for these specific situations, and burosumab is preferred in other situations. I think they MEAN that the old treatment is “better than nothing” (as opposed to being ideal) for patients about to undergo surgery or pregnancy/lactation, but the statement is ambiguous.
Finally, I take issue with the way the authors distinguish between symptomatic and asymptomatic patients. I’ve heard that some XLHers will have blood phosphorus levels barely into a normal range occasionally, but that’s not the “symptomatic” that the article is referring to, I believe. Instead, it’s the other symptoms, the ones that follow on from the low phosphorus levels, that they’re referring to for determining whether a patient is symptomatic/asymptomatic. And I don’t believe there are any asymptomatic patients (unless they have permanently normal phos levels, and then I have to wonder if they were misdiagnosed), just patients whose non-blood-level symptoms are so slow-moving or so “normal” in that person’s experience, that they just don’t notice them. Making the symptomatic/asymptomatic distinction is inconsistent with XLH being a progressive disorder. That progression is always happening in the background (assuming our phosphorus levels aren’t consistently normal), even if we don’t notice it due to the slow pace or the patient being in denial or coping tools that minimize the patient’s awareness of the progression.
Strengths: The article’s conclusion matches what other experts have said, and presumably repetition will assist in getting the message across to those who are reluctant to hear it: “Individuals with XLH often experience unmet needs throughout life; a multidisciplinary approach involving different specialists, is recommended. The new treatment with burosumab can provide an effective and safety therapeutic option in reducing the burden of the disease in both children and adults.”
It’s also encouraging to see that the experts on the panel were not limited to those who treat children, which could have led to skewed conclusions.
Despite the use of the term “conventional” noted above, Statement 13 is otherwise good: “Conventional treatment should be considered only when burosumab cannot be administered.”
And finally, despite the authors making what I think is a false distinction between symptomatic and asymptomatic patients, I’m encouraged by their conclusion that patients should be treated with burosumab for the entire lifespan, not discontinued either at the end of bone growth or at age sixty-five (as is done in Italy apparently, so patients dealing with osteoporosis can also deal with inadequate phosphorus too). The authors note that the benefits of burosumab beyond the initial growth and maintenance of bone structure, include “prevention of osteomalacia and the related risk of fractures/pseudofractures, and improved muscle and joint pain and QoL [Quality of Life], by continuing burosumab beyond the age of 65. Therefore, the experts’ panel believes that the reimbursement criteria for burosumab should be revised to ensure that the benefits gained from burosumab treatment during childhood and adolescence or prior to age 65, are not lost.”
Bottom line: I’m being nitpicky here, because I think that some mental habits (terms like “skeletal disorder” and “conventional treatment”) need to be challenged, and the best way to do that in the medical research and writing setting is by including a process for patients to comment on the articles pre-publication. That means including patients on the expert panels, and including us on IRBS (for interventional and observational studies), and including us on peer review panels. As best I can tell, based on the authors’ credentials and the lack of any acknowledgments of patient advocates’ involvement, there was no engagement with the patient voice for this article, which could have guided the authors to do some deeper thinking about some of the terminology so it would be more patient-focused and would avoid perpetuating old myths (i.e., that phos/calcitriol treatment is effective and risk-free).
Say it with me, everyone: “Nothing about us without us!”
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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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