Often times, real life scenarios in Pharmacy school were verbosely explained and coated with sugar like Saturday morning cereals. When I ran out of options for my uncontrolled Multiple Sclerosis (MS) and had to become a lab rat in a clinical trial, I quickly learned I had been taught nothing useful about trials or perchance I had slept through the lecture ‘How to be a Science Experiment’ in class. However, my knowledge grew exponentially when my MS forced me to step through the looking glass and enter a study.
I was so excited for my second year of pharmacy school in September 2003, until my eyesight decided to go dark in late summer and a shadowy curtain was dropped on my world. The optometrists had me follow a little red dot and hit a button when I saw it which was completely pointless and a waste of time. My lack of vision formed a big black period, causing him to shake his head regretfully and refer me to a neuro-ophthalmologist. After steroids, a lumbar puncture, and a MRI (Magnetic Resonance Imaging), my life was permanently turned upside down with a sentence of MS. Placed on an interferon, I was referred to the Neurology clinic and hustled out the door.
In the beginning, I averaged one or two relapses a year but was always able to bounce back after an infusion of steroids. I believed I had complete control of my MS when I graduated with my Doctor of Pharmacy degree (PharmD) in 2006, but the blinders were soon ripped off when the adrenaline that had been propelling me through school wore off, and I suffered two severe relapses shortly into my residency. A new MRI revealed the lesions on my brain and spinal cord had dramatically increased in quantity over the past four years. I was still on my original interferon beta-1b, and it had obviously overstayed its usefulness.
In 2008, there weren’t many therapies on the market yet, so I had few options. Having recently changed neurologists, he proposed I consider a clinical trial, but my husband, Arman, and I were skittish of this suggestion. We had considered this road with the Natalizumab (Tysabri) trial. However, the week before I was to join, it was removed from the market because of its association with progressive multifocal leukoencephalopathy (think MS on steroids). Arman was leery about me trying something without a proven history. I was a little more trusting, but only because I knew this was the only way to obtain data for approval of a medication. After explaining a Phase 3 trial should be safer since the previous two phases identified the majority of side effects, Arman reluctantly agreed.
We decided that I would join the trial for Alemtuzumab, which was already on the market to treat chronic lymphocytic leukemia (CLL) under the name Campath. My neurologist informed us this was the second enrollment of the trial, and the first had shown good results with very few adverse events. I would have the infusion once a year for two years and then be followed four more with physicals and labs.. This medicine sounded unbelievable; only two years of treatment and then nothing else needed? I allowed myself to be cautiously hopeful.
I began the process of signing consent forms, having initial blood samples drawn, and preliminary neurologic exams. This was all part of the in-depth entrance exam to be in the study. Knowing to expect this didn’t change the fact that I felt like I was trying to get accepted into a private club where I would be served the good ‘candy’.
My initial blood work showed a low CD4+ T-lymphocyte count, which would exclude me from the study i.e. my test scores weren’t high enough to gain acceptance. However, I was informed that there had been some reports of low CD4+ being associated with long term interferon beta-1b treatment. The study investigators decided to include patients with initial low counts if they normalized after the washout period. I was saved on a technicality as long as my test scores improved. I had been wait listed. Yay!
The next step before I could even begin the physical entrance evaluations was to undergo a 30-day washout period, during which I could take no MS disease modifying medications. One month? Shoot! This was going to be a piece of cake. What could possibly happen in one piddily month?
The first weeks went by with no problems, and I started wondering why I needed any medication at all. Then reality started to creep in like a pungent smell; mild at first but it grew stronger as more time passed. It started as little things: heat affected me quicker, my fatigue increased, and I could do almost naught – less than one thing a day equals worthless. Things that used to be trivial, like scooting on my butt from bed to couch became virtually impossible to accomplish. I wanted to stab an empty syringe in my arm and hope for the placebo effect to kick in. My feebleness physically had shattered me mentally.
After the washout period, my bloodwork showed everything to be in the normal range, so I was deemed suitable. I made an appointment to have my pretreatment neurologic tests and MRI and anticipated beginning my treatment four days later. However, the researchers had made a few adjustments to the consent form, so I had to raze more trees and sign an amended version. Over time, I found out I would be required to autograph a new copy every time the authors changed a single word, thus resulting in a collection of over twenty manuscripts.
By the day of the tests, I could barely walk, even with assistance and my new cane, and if I stood too long, my legs would fold like an accordion despite the stick. Between the washout period, tests, and lag time, it had been almost two months since I had received any treatment, and I could really feel it. They buried the lead about the 30-day washout period. To clarify, it was 30-days before I could even begin the trial’s physical exams, not 30 days until I could begin the symptom treating medication.
Although the study was blinded, when I found out my regimen would be a six-hour infusion, for five days, I knew straightaway I had been randomized into the Alemtuzumab group seeing as it was IV and the control, interferon beta-1a, was a subcutaneous injection self-administered three times a week. Elated at my good fortune, I could only cross my fingers that it worked, because I couldn’t feel my toes by then.
I was also told housing would be provided at a nearby hotel for Arman and me, which was great news. When I had started to lose feeling in my legs and feet four weeks back, Arman decided it wasn’t safe for me to drive and began taking time away from work to transport me to and from my countless appointments. Being able to subtract the daily sixty-mile round trip drive from the five, already lengthy, days of treatment, would greatly help.
After enduring almost eight weeks without medication, or what felt like three years in MS time, my first day of treatment finally arrived. The itinerary was methylprednisolone for the first hour on days one through three followed by the study drug over six hours on days one through five. Then I had to stay at least an hour after the infusion to be sure boredom was the only adverse effect. It baffled me why no steroids were given on day four and five? Were they trying to evoke side effects on the last two days to enhance their study? As troublesome as this thought was, I chose to focus on my nervous anticipation of receiving a potentially life changing medication and my naïve optimism that it would wipe out my MS symptoms.
Day one seemed to start fairly well. Following the methylprednisolone, I was given metoclopramide and diphenhydramine; the latter knocked me out, and I snored through most of the study-drug infusion. When Arman came to pick me up, I was able to make it to the car with assistance, but when we arrived at the hotel, I wasn’t strong enough to stand. Arman pulled me from the CR-V and helped me to the comfortable green wire bench by the sliding entrance door where I took my first pit-stop. I had to pause in a firm, blue lobby chair next, before finally making it into the elevator. As the doors closed, I leaned against the metal wall and slowly slid to the floor as my gas tank hit zero and the confusion and anguish crept in. I thought the infusion today was supposed to make my legs stronger, not jelly?
Every part of me hurt. My muscles weren’t responding to my brain, and my brain was too garbled to realize it. When the doors opened on our floor, I scooted out the door and squirmed like an inchworm down the hall. As I hauled my drained body across the carpet, I laughed and jested about how absurd I would look to anyone who rounded the corner, which exasperated my already tired, frantic husband. Months later I confessed that if I hadn’t laughed at the situation, I would have dissolved into a drippy puddle of emotion and knew he wouldn’t be able to handle that after seeing the anguish and helplessness in his eyes at that moment.
When I finally made it to our room, he helped me wiggle my way onto the double bed’s flower print bedspread, and I curled into a ball, praying for sleep or death, whichever took me first. Arman called the study coordinator who was surprised to hear about my reaction and agreed to deliver a wheelchair to the hotel the next morning. For the rest of the week, I was transported everywhere in the borrowed chariot.
On day two, the study site’s lead physician came to see me during my infusion. Answering him honestly when he asked how I was feeling, I told him how weak I was and about cleaning the hotel hall with my bum the previous night. His response, “You’re going to feel like crap. Nothing we can do to prevent that.” The investigator’s candor misled me into thinking this reaction was normal, but, turns out, it wasn’t. However, for some reason, his words helped strengthen my resolve for the forthcoming trials. So far, things were off to a disconcerting start, and I was worried days four and five might be worse when I received no methylprednisolone. I wanted to prepare myself now for this possibility.
The rest of the week progressed as expected. I developed hives, but not as bad as I had feared. The weakness, fatigue, and muscle pain had already debilitated me on the first day, so noticing anything different was difficult. Sleeping both in and out of the clinic, I triad staying comatose to help me ignore all the physical and mental agony I was experiencing. The nurses kept telling me the medication should start taking effect soon, but I dejectedly knew I had flunked out and was overcome with hopelessness.
A small number of earlier patients had developed immune thrombocytopenia purpura (ITP), so I was to be monitored for this with a monthly blood draw and online survey. Answering “yes” to a question suggesting a symptom indicative of ITP would prompt additional bloodwork. I also had to see two-study neurologists (one blinded, one not) every three months, complete mental/physical health surveys, and have yearly MRIs. When I was wheeled out of the clinic on the last day, I was handed a calendar for important dates, depictions of what to look for with ITP, and a 24-hour telephone number to call if I had any problems. Leaving the office, I was in worse shape than I had arrived in after five days of misery. This was the first time I felt completely defeated and demoralized by my MS.
The first few weeks were excruciating. During the initial days, I was covered with red, bumpy hives and wanted to scratch my skin off. I developed ulcers in my mouth and couldn’t eat or drink without agonizing pain. The weakness and fatigue increased to the point that I could barely stand or stumble to the restroom. Between struggling to survive another day and cursing the one I signed my first consent form, I hardly noticed three weeks had gone by until the ITP survey reminder arrived in my inbox.
Before I opened my laptop, I was already set-up for failure on the questionnaire. A few things I needed to look for that could indicate ITP were increased bruising, red dots or petechiae, and fatigue. Naturally pale as Casper the ghost, I bruised if I hit a wall too hard. Also, I was always fatigued and covered in polka dots because my hives hadn’t cleared up. These all skewed my answers and when added to the weakness and immobility I was still experiencing, I won a trip for more bloodwork. Thankfully, the results were normal, and I was sent out unto the world for another month.
After suffering through six-weeks of washing the poison from my body, the after-effects of the infusion were fading, my MS was flaring, and my sanity was waning. My neurologist gave me a steroid bolus in hopes of granting me some relief and to prepare me to begin my medication search again. It was infuriating that my body had suffered significantly from this medication but my MS had come through unscathed. Alemtuzumab had been as effective as a six-hour bolus of normal saline for me. Due to my adverse reactions, I only received one-year of the two-year regimen and was no longer on the medication, but was still followed for four years. However, this turned into twelve when the study was extended to look for long-term side effects.
Throughout the trial, I was compensated, however, a hotel room and $35 a visit did not adequately cover the pain, suffering, and emotional/physical toll we endured, in my book. Arman was brutally traumatized from watching his wife weaken right in front of him and go from walking to crawling, literally, in a matter of minutes. I was haunted by the nightmare of this struggle and felt responsible for inflicting this anguish on him. In a mere five days, this experience left us both with permanent scars.
Despite my wicked reaction, Alemtuzumab was FDA approved under the name Lemtrada in 2014. My sacrifices could not be quantified when my entire personal journey was transformed into a faceless number and converted into a final percentage. All my misfortunes, agony, and anguish were simply rolled into ratios and displayed on the package insert. Even though I knew this was how studies were reported, it was disconcerting to see everything I went through boiled down to pharma talk. I had become nothing more than a “Rare but Serious Side Effect”.
Author: Katie Yusuf
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