A Single Data Point of Failure

Over two years ago I was put on Remicade (infliximab), a TNFa immune blocker, to control my Crohn’s disease. Two of the main biomarkers they use to measure inflammation with IBD is C-reactive protein (CRP), a protein released by the liver as a response to inflammation, and erythrocyte sedimentation rate (ESR) which is the rate at which red blood cells sediment in a period of one hour. My CRP has been measured over 100x normal levels and ESR at 6x normal levels, making inflammation my superpower, or perhaps, more accurately, a response to some unknown kryptonite.

Tumor necrosis factor (TNF) is a master regulator of cell-to-cell communication in the body as a response to infection and has been shown to recruit and activate immune cells. This discovery made it a prime target for therapy and has been effective for a range of autoimmune diseases, though comes at a cost—shutting your immune response down also reduces your body’s resistance to infection. Additionally, it is not well understood how this blocks the effects of other signaling done by this cytokine for things like cell apoptosis (the natural death of cells) and lipid metabolism, which is crucial for breaking down fats and converting them into energy in the liver.

The way infliximab works is that it binds to the TNF alpha receptors, in effect blocking the communication signals to fight off infection, reducing the inflammation response. For my extremely high levels of inflammation, we found out early on that I burn through medication about 2x the normal rate, so I get these infusions every five weeks.

The efficacy of the infusions in my recovery is a bit mixed, I have maintained 5x-10x normal inflammation levels throughout my treatment, but have suffered fewer complications like fistulizing. Fistulas are “tubes” (fistula is Latin for ‘pipe’) connecting spaces or organs of the body, typically leading to an abscess. While not totally uncommon in Crohn’s, I have had six surgeries to fix fistulas, some associated with extreme metabolic abnormalities and morbidity from septic complications, making me a rare case.

I believe the Remicade was able to control complications enough that the research (genetic, microbiome, metabolic) and biohacking (ketosis, autophagy, mitochondrial restoration) I was doing would start to pull my health back from the Titanic disaster that always seemed to loom ahead. In 2018, the work started to pay off as my condition reversed from about 80% of my large intestine being severely diseased to no active disease and a declaration of remission from my doctors. The Remicade had provided a life-raft in a vast ocean, but not a ship to sail home on, that was up to me to build.

At the end of 2018, my insurance decided I need to switch to a “biosimilar” Remicade medication, Inflectra, which had been approved in 2016 for the same uses. Biosimilar doesn’t mean the same, it simply means that they have shown scientific similarities, not necessarily clinical data to the product they are trying to replace.

Since receiving my first infusion of Inflectra, I have documented symptoms with the infusion nurses of a tour of autoimmunity starting with a sort of polyarthritis (multiple joint swelling and pain), followed by psoriasis and bowel pain. The response typically lasts 3–7 days, meaning for 1 week out of my 5 weeks I am not very functional, ill and in varying degrees of pain. My gastroenterologist has been trying to make the case to insurance that I should be switched back to the Remicade, but so far that has not happened.

This week I had my latest infusion and woke up the next day with what seems like uveitis, or inflammation in the uvea affecting eyesight and causing blurring, that oscillates in and out, subsequently causing dizziness and disorientation as my brain tries to calibrate from the change in vision.

My nurses at Stanford believe that people react to the preservatives, stabilizers and thickeners in biosimilar medications, which can include compounds of varying quality, like complex sodium dihydrate phosphates and polysorbate 80, an emulsifier shown to exacerbate dietary factors for people with Crohn’s (https://gut.bmj.com/content/59/10/1331.full).

As I wrote above, pharmaceutical companies don’t have to go about retesting the medication in a clinical setting if they can show scientific similarity. The burden is to show efficacy in at least one of the proposed treatments and then get fast-tracked for the others. Inflectra was not tested on people with Crohn’s, only rheumatoid arthritis and Ankylosing Spondylitis. In fact, in 2014, Health Canada did not approve Inflectra for inflammatory bowel disease (UC or Crohn’s) because they could not rule out causing a “mechanism of action” for IBD complications. In the U.S., Inflectra was approved “as biosimilar, not as an interchangeable product” in 2016 and is now given to thousands of IBD sufferers to save ~15% over the Remicade.

Considering the insurance company could have purchased a small island for what it has had to pay for my care over the last six years in treatment, surgeries and medication, saving a few bucks to create complications that didn’t exist seems counter-productive. I am left to question whether to continue getting treatment, suffer quietly or roll the dice without. Like most things with autoimmune diseases, the effects and toll remain largely unknown outside of one’s own inner landscape or immediate loved ones.

Epilogue

Autoimmunity is one of those places in medicine that is often failed by the standard of care and by the medicine-as-profit environment in the United States. We truly understand little of what is causing an autoimmune response, the interrelatedness of symptoms and diseases and how to best treat them. Our immune systems are designed to protect, not break down, so autoimmunity represents a major glitch in the system. Treating symptoms, whether we are talking leaky gut, sore joints or cognitive decline in silos from all of the other metabolic complexity might mean temporary relief, but also reinforces the notion that autoimmunity is incurable and sufferers will eventually succumb to the effects.

Discovering and addressing the source of an immune response is a daunting task which I why I believe that biohacking and citizen health is a critical component for the future of addressing autoimmunity. Those living with these diseases have an intimate map of the multi-factorial nature of the autoimmune response — stress, environmental triggers, food, toxins and parasitic, or fungal invasions. In successfully hacking my disease state with the help of a variety of brilliant folks that cover research, medical and nutritional disciplines, I have seen a connective thread and how we might, as individuals take charge of our own future. The emotional, physical and mental space of this task is a bit like snowboarding on an avalanche - you have to stay on top of where you are while being open to a rapidly changing environment-where what is working in one moment may be totally irrelevant in the next. While my disease has been in remission for nearly a year, the curse of getting well is the fear of becoming sick again.