sungo> doctor quote of the day: survivable does not mean tolerable
r> oh, were you discussing Highlander 2?
sungo> I’d prefer a marathon of Highlander 2 to what we were discussing.
g> that is a visceral choice of the options at stake Oof
My rheumatologist, at my most recent follow-up, asked me to detail my current condition and how the meds are treating me. I talked about my experiences with subcutaneous methotrexate, my newfound preference for 1 mL syringes, how I feel like I am responding well to subq. I also talked about how I am still clearly not in remission. I’m close, so close, but not there yet. I talked about the daily horrors that my digestive system is putting me through. Here, my doctor started getting a bit agitated and eventually broke in. “This is intolerable. We need to consider rituximab.” <record scratch> My symptoms are improving. My symptoms are nowhere near “organ/life threatening”. How could I quality for rituximab? The doc said “survivable does not mean tolerable. You are surviving the medication. Your body is not tolerating the medication.”
And yeah, friends, when I sit and think about it, I’d prefer a marathon of Highlander 2 to carrying on with how my life is today.
Life with subq mtx
A few weeks ago, I wrote the words “apocalyptic cramps” in my tracking journal. On that particular day, I took my injection of MTX and, starting 1.5hrs later, I had cramps bad enough that I could see god. These were PMDD level cramps, repeatedly over the course of four hours, combined with what you might imagine were pretty horrific bathroom times. This was not the first time. Not even the first time that month.
But it’s fine because the brain fog is (probably) gone, the general muscle pain is much lower, and I feel decent most of the rest of the week… if you ignore the fun bathroom times every morning for two to three days following MTX. It’s fine because I’m not getting the blackout migraines I used to get from oral MTX. Except I am getting pretty bad occipital neuralgia (which is of course different than a ‘migraine’) throughout the week, just not “lie in a dark room and hope for death. a quiet death with no bright lights”. Except that once.
The thing about having a medical tracking journal is I have notes in my own handwriting, that I remember putting to paper, with all of the details. These are only the bits I thought abnormal. I’ve normalized so much stuff, usually gut or neuropathy related, that I just don’t even write down anymore. When people who are not me read or hear my status report, they get … upset, sad, a particular far off stare. It is clear that, even for all the recent gains, I am reporting status from at least a minor hell.
Life with subq mtx is much better than it was with oral mtx. But I am still homebound, miserable, constantly symptomatic (or full of side effects) and exhausted. And resigned to my fate. Because the GPA isn’t trying to take my major organs yet, thankfully, so I simply, don’t qualify for any of the other intervention options. I put that out of my mind and got on with the business of surviving.
Turns out I was wrong. Turns out that failure to tolerate MTX is qualification for rituximab, potentially.
Who knew?
Rituximab
Rituximab is a monoclonal antibody that suppresses CD20+ B-cells, a type of white blood cell. The general theory is this suppression disrupts the production of ANCA, the antibody by which my body attacks itself [1]. (Now, to be fair, the current research suggests the neutrophils being targeted, at least some of them, are seriously fucked up and deserve their fate [2]. But that’s a separate problem.)
Studies show that Rituximab is as effective, at least, as MTX in achieving remission, moreso than the older options. There are two problems, though. First, for most folks, MTX has less side effects. Second, the side effects that MTX has are less dangerous.
When you say dangerous…
Rituximab is given as an infusion, four to six hours, usually, not including prep work. It’s a full day in the chair in the infusion center under direct medical care. So it’s already special (and more costly).
The NIH’s list of adverse effects is something else, by which I mean “terrifying” [3]. One study found that 57% of patients (203 out of 356) suffered grade 3 or 4 (severe to life threatening) toxicities [1]. That same study found that reactions to the infusion itself were most common and 80% of all fatal reactions occured with the first infusion.
Rituximab’s entire job is to suppress production of a type of white blood cell, so lymphopenia and neutropenia (not having enough white blood cells to fight off infections) are real concerns.
To summarize, Rituximab could kill me the first time out. If not, the secondary infections might.
But my absolute favorite “adverse effect” is that prior viral infections can reactivate. Herpes, Hepatitis B and C, West Nile, Chickenpox, and others. And why yes, I had chickenpox as a kid and did not have a fun time. There’s a real risk that, while taking rituximab, I could fucking get chickenpox again, or develop shingles.
“Relatively safe and well-tolerated”
“Rituximab is a relatively safe and well-tolerated drug” [3], according to NCBI. A systemic literature review in 2019, including nine trials related to ANCA-associated vasculitis, stated that “studies providing data about AEs [adverse events] showed comparable rates of incidence between RTX and the control groups” [4]. Single center studies corroborate the safety and efficacy of Ritxuimab [5], [6].
The scare sheet for Ritxuimab is no fucking joke, for sure, and the risk of infusion reactions in particular is quite real. But this is why ritxuimab is delivered via infusion at an infusion center, supervised by medical professionals. Most infusion reactions can be managed by slowing the rate of infusion or by administering acetaminophen or intravenous antihistamine [1]. To quote Buch et al, “Severe infusion reactions leading to drug discontinuation are uncommon (<1%) and are mainly restricted to the first infusion” [7]. My HMO’s guidance for rituximab indicates a whole fun bag of preparatory medications to cut the risk of infusion reactions [8].
Cytopenia is reported in up to 8% of patients in the oncology literature but very rare for autoimmune patients, “for unknown reasons” [7]. Tesfa et al found, however, in one cohort that the rate of neutropenia in GPA patients was potentially significantly higher than RA patients (23% vs 3% respectively) [9].
Buch et al also note that low baseline levels of IgG, including before rituximab administration, as being associated with an increased risk of serious infections [7]. My immunoglobulin numbers are kinda shit on their own, apparently, per my quarterly blood work. They are high enough to begin treatment but low enough that my doctor and I have already discussed intravenous immunoglobulin as an option.
What would Europe do?
To quote the 2022 update to the EULAR recommendations for the management of ANCA-associated vasculitis [10]:
“For induction of remission of non-organ-threatening or nonlife-threatening GPA or MPA, treatment with a combination of GCs and RTX is recommended.”
“[T]he use of RTX over MTX or MMF should be considered in patients with GPA and MPA even without organ-threatening manifestations as RTX-based induction and remission regimens are associated with higher rates of sustained remission and lower GC exposure.”
“For maintenance of remission of GPA and MPA, after induction of remission with either RTX or CYC, we recommend treatment with RTX.”
The American College of Rheumatology disagrees [11]. The difference lies in the amount of studies specifically related to non-organ-threatening GPA and the use of MTX and RTX. There are lots of specific studies pertaining to MTX. The RTX studies however have focused on severe cases. “Methotrexate is currently recommended over rituximab because of the larger body of evidence and clinical experience with methotrexate treatment for this patient group; clinical trials are needed to compare their efficacy” [11].
And ultimately, methotrexate does not have a box warning for maybe killing you in the first 24 hours. Let’s be real, that warning puts a huge damper on any rituximab conversation. Further, MTX can be given at home with pills and most often is for GPA patients. “Take some pills and let’s see how we do” vs “spend one day a week at an infusion center for the next month or more” is also a challenging conversation. That is a lot of time off work and here in the States, where our social safety net is almost nonexistent, it’s a very difficult sell unless you feel like you’re dying.
The Plan
So what’s the plan? Well, we’ve tried it the American way. Now it’s time to try the European approach. We’ll try rituximab. I would regret not trying, even with all the possible drama. If there’s a chance that I can see my way out of this Highlander 2 years-long marathon, then I need to try. And maybe I end up back on MTX but I will have at least tried to find a way out.
First, though, I need some vaccines. At the very least, I’m looking at the shingles vaccine because, really, fuck chickenpox and shingles, and the Hep-B vaccine just to be sure. Then there’ll be a couple weeks off of MTX to let the vaccines do their thing. And on to ritxuimab at the end of January.
But I have to admit it. After all this research and typing, if you haven’t noticed, I’m terrified. I’ve written this whole post to help myself build a narrative around this course of action. To help me have data and case histories and facts so I can get my head around this idea that I am going to sit in an infusion center and take a drug that could kill me on the spot on the hopes of … well, there are a lot of hopes. The hope of having a life again. Of not spending the next few decades of my life exhuasted and miserable and full of GI side effects.
I know the infusion center I’ll be visiting. My partner is a relatively recent cancer survivor, including a full run of chemotherapy. They received treatment at the same center I’ll be visiting. I sat with them at the beginning and end of their chemotherapy. And now I’ll be in the big chair.
It’s… a lot and I don’t know that I’ll be mentally settled until the moment I sit in that chair and give my consent to begin treatment. Until then… I’m going to be staring into space a lot, I think.