002 - Spoons
This post was supposed to start below, but I need to update you all on the insurance front. Based on the initial meeting with CBCI, we should have received a proposed treatment calendar at the end of this past week. On Thursday, the CBCI Transplant Coordinator called to inform me of their struggle to get my insurance company to officially approve the transplant. The issue is centered around me being a (unnamed insurance company) of Washington customer and all of the approvals are being sent to (same unnamed insurance company) of Colorado; we can thank the Affordable Care Act for this state line BS. Colorado is afraid to approve it because they aren’t financially liable for it, Washington is. Is it a cluster? Absolutely, but that’s par for this course. I am hoping that by the end of this next week the two insurance companies can get their act together so I can get the proposed calendar (and share it with all of you).
A New Baseline
Understanding a patient’s baseline is a key part of the clinical observation of MS. A provider must understand a patient’s symptomatic baseline before and after a relapse or flare. One characteristic of RRMS versus the Progressive forms of the disease, is that most patients return to a normal baseline after the first relapses. For example, my return to a normal baseline after clinical relapses in 2009 and 2014.
Disability and symptoms in MS are clinically measured using a tool called the Expanded Disability Status Scale or EDSS. This scale goes from 0-10, with zero indicating a normal neurological exam and ten being death caused by MS. There are a total of 8 CNS functional systems: pyramidal, cerebellar, brainstem, sensory, bowel/bladder, visual, and cerebral. After returning to baseline after my first relapse post Dx, I was about a 3.0 on the EDSS. While still ambulatory at baseline, the main driver of my EDSS score is the number of affected Functional Systems (FS). The symptoms experienced at baseline (post 11/19 relapse) were balance and coordination challenges; sensory symptoms of left foot drop, leg and saddle numbness; bowel/bladder symptoms of constipation and neurogenic bladder; diplopia for visual symptoms; and lastly cerebral symptoms like memory loss, attention, emotional and awareness issues.
The Spoon Theory
In 2003, Christine Miserandino was at lunch with her college roommate when she was asked what it was like to have Lupus. What eventually came out of this conversation has been developed into what is called Spoon Theory. Lupus, like MS, is a chronic autoimmune disease where the body’s immune system mistakenly attacks healthy tissue. Lupus is known as “the great imitator,” in that it is extremely difficult to diagnose because it imitates other diseases, even MS. Like several other autoimmune disorders, fatigue is a major symptom of both MS and Lupus.
Here is an abbreviated explanation of Spoon Theory. Someone who has a chronic illness (like MS or Lupus) has a finite amount of energy, or spoons, in a day. If a ‘normal’ person has a nearly infinite supply of spoons where I might have ten to twelve to use per day. Getting dressed, showering, making breakfast, sometimes even getting out of bed in the morning will cost me a spoon. If I use too many spoons in a day, I can get a loan of a spoon or two from the next couple of days. I just have to pay interest. So, instead of twelve spoons for the next three days, I only get eight or nine. Now think about how hard the next couple of days are going to be with an even more limited amount of spoons. That is what it is like to live with a chronic illness like MS or Lupus. Granted, I didn’t do Christine any justice. You can read her original essay from 2003 here. This positively impacted the way I approached living with my disease. It helped me understand why my body reacts the way it does and how to conserve energy.
New Neuro, New Relapse, New Year
Following the November relapse, Whitney and I had an appointment with my Neurologist again. He commented that he thought my disease was particularly aggressive and suggested that I switch from Copaxone to Rituxan for my DMT. We had a few questions about the new drug which the doctor couldn’t answer. He said (paraphrasing),
“I am a general Neurologist, so I treat all types of neurological patients. I’m not an MS specialist. The majority of my MS patients are stable, taking first-line treatments and don’t have very much, if any disease progression. I think you could benefit from either a single appointment with (My Current Doctor) or even having me transfer you to their care. They are a specialist and I think you would benefit from seeing them.”
After the appointment and discussion, I asked to be transferred to the specialist. Whitney and I thought that it would be the best path forward. The referral was approved by my insurance and we set-up my initial appointment with the practice’s PA on New Years Eve.
Two days before Christmas, I woke up with major spasticity and numbness in both of my legs. My double-vision was worse than normal and I had no energy. My new neurologist was already on vacation for Christmas, so I was asked to go to the emergency room. I arrived at the hospital, got checked in, and was taken back to a room. Then this smoking hot charge nurse (my wife) came in to help me get changed into a gown. The physician conducted a neuro exam and confirmed another relapse. I had the first dose of steroids in the hospital that day, meaning I got to spend Christmas Eve and Christmas Day getting the other two doses.
A brief aside on steroids: methyl prednisone (steroids) is used to treat acute MS relapses because of how effective it is decreasing inflammation by suppressing the immune system. A relapse is caused by the immune system going into overdrive and mistakenly attacking the CNS. Therefore, steroids are given to reduce that inflammation with the goal of shortening the relapse and limiting permanent neurological damage. Sounds amazing, right? It. Freaking. Sucks. Roid rage is one-hundred percent real. If you have ever been prescribed the little Prednisone blister packs with either 4mg or 10mg doses, you will know exactly what I am talking about. You become irritable, get the munchies, you are restless, and cannot sleep. That first day, you are taking a maximum of 70mg of steroids and tapering down by 10mg per day. When you get an infusion of steroids for MS it isn’t 100mg or even 200mg, no. You (and everyone around you) are lucky enough to get three doses of 1 gram (1000mg) plus the blister pack to taper you off of the high-dose infusions. I totally feel like the below video after getting a gram of steroids. I also get super irritable and eat Cinnamon Toast Crunch like it is my job; flare/relapse Aaron is not fun.
New Year’s Eve was celebrated by meeting with my new Neurologist’s office for the first time. This evolved into both an establishment of care visit with a side of a hospital follow-up. We discussed different treatment options and my previous Neurologist’s plan for Rituxan. The PA vehemently disagreed. They believed that I should try Tysabri instead of Rituxan (slash its newer twin brother, Ocrevus) because it was too aggressive of a treatment for me this early. The PA ordered additional labs and scheduled me for an appointment with my new Neurologist on March 2nd.
How Effective is a Stem Cell Transplant?
Autologous Hematopoietic Stem Cell Transplantation is effective at levels that pharmaceuticals can only dream of being. An upcoming post will be focused on business of treating Multiple Sclerosis and why this is not being offered to more patients like me. Dr. Burt’s groundbreaking MS trial comparing aHSCT to best-available DMTs made waves in the MS community following its January 2019 publishing. If you would rather read an article versus a scientific journal, check this out.
There are two main criticisms of this study. The first criticism is that the sample size was far too small because the trial only included 110 patients. The second criticism is that it was conducted prior to the approval of, and therefore did not include, both Ocrevus (ocrelizumab) and Lemtrada (alemtuzumab). I was presented this argument by a physician to which I argued that we know exactly how Lemtrada performs against the interferon DMTs. These are the same interferons which were included in Dr. Burt’s trial. The criticism over Ocrevus is particularly disingenuous. For one, the TISCH MS Research Center of New York has been using Rituxan (rituximab) off-label for years to effectively treat their patients.
Here is dirty view into the pharmaceutical industry. Rituxan is manufactured by Genentech and was originally approved to treat NHL. Later it was approved for other autoimmune disorders, like RA. Genentech was presented with a real problem: Rituxan’s patent was set to expire in 2018. They made sure that the new version of Rituxan, called Ocrevus, would be approved just under a year (3/2017) before the patent on Rituxan ran out in 2018. Is there a difference in the efficacy of the two drugs? No, there is not. What is the difference between Rituxan and Ocrevus? Rituxan is a murine (mouse) chimeric monoclonal antibody. This means the antibody contains some mouse protein and some human protein. Ocrevus is non-chimeric, so the antibody contains only human protein. That’s it. Now, according to Genentech’s Medical Director of Neuroscience there are differences between the two therapies:
“Although Ocrevus and Rituxan both target CD20-positive B cells, they are different molecules in their structure and how they interact with the immune system.”
Genentech’s claim is that the two drugs bind to “overlapping but different” proteins on the CD20 molecule. This “enables” the ocrelizumab antibody to more effectively bind to the patient’s B cells. The whole point of using Ocrevus or Rituxan is to eliminate B cells and keep them from repopulating. These two drugs have the exact same mechanism of action. If interested, you can read this journal article about B cells and their role in MS.
So, the trial. There were a total of 110 patients randomly assigned into two groups of fifty-five. The “control” group would receive their current DMT until the disease progressed, then they would be transitioned to a more aggressive DMT. The HSCT group received nonmyeloablative aHSCT at Northwestern University, or at a partner institution located in the UK, Sweden, or Brazil.
After the first year only one of the fifty-five patients (1.82%) in the transplant group had any disease progression, compared to forty-four of the fifty-five patients (80%) in the control group. There was also an unexpected benefit: the transplant group had an average reduction of their EDSS by 1.02 points. The transplant didn’t just halt the disease, it made the patients less disabled. Two years into the trial there were now three patients (5.5%) in the transplant group who experienced a relapse and/or disease progression compared to a total of forty-nine patients (89.1%) in the control group. After five years at trial completion, only twelve patients (21.8%) in the transplant group had a relapse and/or disease activity compared to fifty-four patients (98.2%) in the control group. Just over three-quarters of the patients in the transplant group still had no disease activity at 10 years. This is confirmed by the clinical results from clinics in Mexico and Russia. Dr. Ruiz Argüelles and Dr. Gómez-Almaguer have transplanted over 1,000 MS patients at Clínica Ruiz in Mexico. Their results demonstrate a 78% rate of efficacy with a treatment-related mortality rate of >0.25%. More than 2,000 MS patients have been treated in Moscow by Dr. Fedorenko with an overall efficacy rate of 90% for patients with RRMS. This drops to just under 70% for patients with progressive forms of MS.
US Clinical Trial - 78% Efficacy
Clínica Ruiz (Mexico) - 78% Efficacy
AA Maximov (Russia) - 90% Efficacy*
*figure excludes PPMS and SPMS patients
What’s Coming?
This particular post is ending, in the chronological sense, around late-February of 2020. Everything up until now has been boring as hell. I completely violated Stephen King’s rule about a backstory. Well, fuck it. The following posts get way juicier. I will go into things like the conversations with my doctors about HSCT, their opposition to it, and the multiple reasons why (don’t worry, it involves $$$) they are opposed to it. Lastly, watch out for a post focused on the business of treating versus curing chronic diseases like MS, type 1 Diabetes, systemic Scleroderma, systemic Lupus, and CIDP.
Have a wonderful week. Happy February.
- Aaron
What Am I Consuming
:: PODCASTS ::
Pretty light week for me on the podcast front. Other than listening to The Fifth, I started listening to some of Lex Fridman’s content. If you don’t know anything about Lex, he is an AI researcher at MIT working on autonomous vehicles and machine learning. He is beyond brilliant.
Lex Fridman Podcast - Episode #157 with Natalya Bailey: Rocket Engines & Electric Spacecraft Propulsion
The Fifth Column - Episode 224 “MTG v AOC, Merit is so Racist, Determined Incuriosity”
If you do anything, listen to the last 35 or 40 minutes of this:
:: MUSIC ::
:: BOOKS & WRITTEN CONTENT ::
I just picked up The Revolt of The Public by Martin Gurri for my book club (I know, nerdy AF) which is highly rated both on Amazon and Goodreads. I’m excited.
