As of next week, I’ll have been on burosumab for ten years!
Somewhat to my surprise, it’s not easy figuring out what that means to me, so this is going to be a longer and more personal essay than usual, and I hope you’ll bear with me while I try to understand the experience.
Ten years ago next week, I was at the Yale New Haven Hospital’s human research unit, waiting for the injection that could have been just another in a series of them that had started in January, but that I was pretty sure was the first non-placebo injection. If you’d asked me then about my expectations for the next ten years, I would have had a simple answer: “Not worse.” My expectations have grown more complicated since then.
Initially, my definition of “not worse” had three elements: 1) stop the spread of calcifications, 2) stop the ever-increasing frequency of spinal spasms, and 3) slow the creeping decreases in mobility. I wrote in my diary on the day I started the clinical trial: “[Burosumab] should, at the very least, stabilize my skeletal condition where it is now, which isn’t great, but is better than if it continued to deteriorate.”
I know now, and I’d guessed before I got confirmation after the study ended, that my first six months of injections were placebo, so my first actual dose was indeed on June 30, 2016. My journal contains some speculation over the next few days about whether my fatigue had improved, but nothing about a change in pain levels. In retrospect, I think my insistence that I just wanted to not get worse hid a deeper, unvocalized hope that there would be other, more immediate benefits, probably because I was afraid of being disappointed. Four days after the dose, I noted, “I was really hoping or a more obvious improvement, and not just on the cellular level, but in ways I could actually feel.” (Yes, yes, I know now that it takes a week or more for the blood phosphorus levels to max out, but I didn’t realize at the time and thought I’d feel a difference almost immediately.)
Then, on the sixth day after the injection, instead of feeling better, I hurt all over. Just guessing, but given the time it takes for burosumab to raise the blood phosphorus levels, that was probably when my phosphorus levels finally went into the normal zone for the first time in my life. Initially, I attributed it to a sudden change in the summer weather from dry air to high humidity, which always makes me achey. But by day 7, I was having severe spinal and knee pain and wrote, “I’m going a little crazy and wondering if there are any patients who feel worse on [burosumab]. … I’m feeling pain in places I usually don’t, like my left hip and my left wrist.”
These notes are particularly striking to me, since I don’t usually write about my pain levels in my journal, at least not when they’re just background noise. If I do mention pain, it’s something out of the ordinary, so on day 8, when I wrote “Really hurting,” it tells me I was probably at a10 on the standard pain scale. And again the pain wasn’t, as I’d noted the day before, always in the usual places (my joints): “[There’s] a spot in the middle of my thigh that feels like a bruise, but there’s no discoloration. And sometimes the pain is there and sometimes it’s not.”
At the same time, I’d begun icing my spine, because I was getting multiple, debilitating spasms per day for no real reason. Before the first burosumab dose, I would get a spasm two or three times a week, always when I did something to jar the spine, like driving over a pothole or twisting my spine. (These spasms only lasted a second or two, but they literally paralyzed me, leaving me unable to move or breathe, in addition to hurting at a level of about 15 on a 1-10 pain scale!) By this point, simply breathing normally (not a deep breath, which I couldn’t do at all, just normal breathing rather than rapid, shallow breathing), could trigger a spasm. My mental distress was peaking too: “So frustrating when I’d been hoping for the last six months (and like three years before) that I’d finally get a wee bit of relief and instead [the pain] is getting worse.”
All along, I was increasing my NSAID use to manage the pain/inflammation and intermittently icing my spine, but the treatments weren’t helping, so on day 9 (after 3 days of severe pain and frequent daily spasms: “Pain, pain, pain. That’s all I can think of now.”), I finally put myself on three days of bed rest, lying on an ice pack.
Two days later (day 11), the pain began to subside and I could breathe normally, but I was still very careful not to do anything to trigger a spasm. I don’t know a phrase for the spinal version of “walking on eggshells” is, but that’s what I was doing. Even three days later (day 14), I was still afraid to take a deep breath for fear of triggering a spasm, and I’d been postponing errands for the same reason.
By day 16, I noted, “I’m starting to feel more my usual self. Not ‘good,’ but ‘normal for me.’ Which is painful but functional.” Despite that conclusion, I was “still breathing shallowly to avoid moving my spine.” (You may recognize my description as a classic example of how patients with high pain tolerances will tell you they’re fine, and that their pain level is around a 5 out of 10, but if you pay attention to how they’re moving, you can see that the level is a whole lot closer to 8 or 9 than to 5. As you can see in my journal, I even put on a good face to myself, not just the public!)
There’s no further mention of pain—again, note that I usually only mention in my journals when it’s unusual, better or worse, so the absence of any mention of pain does not mean it went away, just that it was nothing out of the ordinary level—for about three weeks. Then, five days after my second dose, I wrote, “My spine is acting up again, like it did after my first [burosumab] injection. And it would sort of make sense—it happened [the first time] at the 6-9 day mark, more or less. I believe … that peak effectiveness is around then, and it drops off afterwards.” This flare didn’t last long and wasn’t as severe as the first one, because I never mention it again in the journal, and it never recurred with subsequent doses.
If you’re wondering why I experienced that increase in pain, the hypothesis is essentially, that my muscles were wallowing so happily in the abundance of phosphorus they could now access to support my spine in ways it had never been able to do before, that they decided to do a bit of redecorating, rearranging my body a bit. The spinal cord didn’t understand that the tugging and shoving (like a bit of chemical chiropracty) was happening for its own good and responded with some inflammation. But once the spine and the muscles reached a truce, the easily-triggered spasms went away.
I’m sharing these details as a way of showing a bit about the journey. It’s notoriously difficult to remember pain after it’s gone, and I had, in fact, forgotten in the intervening years just how bad the pain was after that first injection. I remembered vaguely that I’d felt worse for a few days, but that once it subsided, later injections didn’t cause that worsening. But I didn’t recall just how debilitated I had been for a few days.
That inability to really remember life before burosumab, to fully inhabit the pain and daily challenges I experienced then makes it difficult to understand what it means to have been on treatment for ten years. I’m often asked what’s different, and I know that the background bone pain is gone, but the absence of pain is hard to define, especially when it’s really just a reduction in pain, since my joints still hurt. I suspect my fatigue levels have improved, but fatigue, like pain, is something we adjust to, and whatever we experience becomes “normal,” and impossible to compare to previous levels.
The only concrete change I can point to is the almost-complete absence of any spinal spasms. It took me something like18 months before I realized that my several-times-a-week spasms had gradually subsided to once a week, once a month, and then so infrequent that I couldn’t remember the last time I’d had one, and it was always because I’d done something stupid to stress my spine. Coming up on my ten-year-anniversary dose (July 2), I’m pretty sure it’s been more than a year, possibly multiple years, since the last spasm.
Another complication for comparing before and after burosumab is that aging is having its inevitable effects on me (I turn 71 within a few days of the tenth-anniversary dose), so it’s hard to tell how much my symptoms and mobility restrictions are due to the progression of XLH and how much they’re due to the natural effects of aging. Especially since the two interact, with the XLH causing the osteoarthritis, and the cumulative effects of inflammation over time (aging) worsen the arthritis. XLH can limit the exercise we should do to maintain muscle function (both because of pain and biochemical muscle dysfunction), but at the same time, aging, by itself, almost inevitably leads to muscle loss.
So I don’t have any really clear personal data on the effects of ten years of burosumab treatment. I’m convinced I’d be more debilitated, but few of our symptoms are objectively measurable, and the measurable ones (fractures and calcifications) aren’t necessarily correlated to quality-of-life challenges as the more subjective symptoms (pain, fatigue, mobility). That leaves us with comparisons of quality-of-life before and after, which are, by their very nature, highly speculative. The XLH community doesn’t have the much-needed data that compares burosumab-treated patients to same-age patients who did not have access to burosumab, so you’ll forgive me for indulging in a bit of speculation. I’d need to be able to observe myself in two parallel universes (one with burosumab, one without) to know for sure, but I firmly believe I would have been in a wheelchair (or worse) and dysfunction from pain medications long before now if not for the burosumab.
And that, really, is the big lesson I wish everyone took away from my experience with ten years on effective treatment: That, in adulthood, treatment is more about PREVENTION of the progression than correction of existing symptoms/challenges. Too often, the prevailing mindset (among clinicians, insurers, and sometimes even XLHers/caregivers themselves) that a patient with mild symptoms doesn’t need treatment. If there are no fractures, no overwhelming pain, no fatigue that can’t be worked through, then no need for treatment. Except that we know the progression of symptoms (especially calcification) is happening, even if it’s not quantifiable. And at some point, the symptoms will go from mild/subjective to significant/objective, and the patient will finally get treatment, but a debilitating amount of damage will have already been done. Additional damage may be slowed, but the patient has already lost the chance to prevent the original damage and will have a permanent reduction in mobility and range of motion.
l hope that by the end of this year, the tenth anniversary of about a hundred patients starting burosumab (and in 2028, the tenth anniversary of burosumab being commercially available in the U.S.), we’ll see more focus in journal articles on the progressive nature of XLH and how these early patients have managed to slow the progression. I think that’s the big message (along with “stop calling XLH a form of rickets”) that the patient community needs to fully absorb and make sure the health care community understands.
Now that we have ten years of data on the burosumab-treated patients (through the clinical trials and the followup data of the patients in the clinical trials), it ought to be possible to begin comparing our outcomes to the outcomes of same-age non-burosumab-treated patients. To do that though, we’ll need a really comprehensive and reliable natural history study that can provide data on patients who were NOT on burosumab over an age-matched ten-year period. Then we can see when patients experienced certain disability milestones (job changes, use of assisted devices, etc.), and can compare those milestones between patients on burosumab and patients pre-burosumab (or otherwise not on treatment).
If I get the chance to report on what it’s like to have been on treatment for twenty years, I’d like to believe I won’t have to look at my journal again, and can just point you to the results of a comprehensive natural history that will, with more facts and less speculation, lay out the experience for me!
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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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