Article No. 420
18 February 2021
Atypical HUS is a complex puzzle for both patients and their physicians, at initial onset of this rare disease but also during subsequent episodes or an aHUS relapse. A scarcity of information in 2003 about this rare disease led me to connect with other aHUS families, first within my own nation (USA) and then around the world. The 1st thing I learned? The best place to find a helping hand was at the end of my own arm. The 2nd lesson? It takes hard work and the dedication of many to coordinate aHUS treatment and care plans. Those two lessons initially may seem to build a bit of a paradox. Not really. It’s the rare disease patient and their family or friends that are driven to find a path to wellness, but in order to follow the path and undertake the journey there must be the support, knowledgeable skill, and dedicated care of others.
With atypical HUS, plan to ‘Expect the Unexpected’. After 10 years of no measurable disease activity, my teen son recently had an aHUS relapse. His genetic testing indicated a factor H mutation, the same aHUS predisposition that manifested as chronic illness in our eldest child but as episodic in the younger son. No two cases of aHUS are alike, even in siblings with the same genetic profile. Given that our family has faced the challenges of atypical HUS for many years, you’d think that we were well prepared for whatever issues might arise during a relapse. In some ways we were well prepared. We had urine test strips at home to detect signs of hemolysis (red blood cells), along with a blood pressure monitor. We’d organized (and kept updated) an ‘aHUS Care Notebook that contained our son’s genetic test results, immunization record, last medical exams, and other vital documents. Our family thought through what an aHUS relapse might mean for lifestyle or changes needed at home, school and work – so adaptations were considered and plans in place, just in case. Unfortunately, aHUS threw us a few curve balls that were unexpected.
Why would my family’s aHUS care plans need flexibility?
Being prepared with our aHUS Care Notebook helped a great deal. Given that my teen son’s relapse happened on a Saturday that was also Christmas day, no Urgent Care centers or stand-alone lab centers were open. A holiday weekend also meant staffing differences. Think through adjustments likely to occur if timing of any relapse means you must be seen by new physicians or treated by medical personnel not familiar with aHUS. That may be especially true for those who travel extensively for business, are at university, or those changing their residence to a new locale. After calling my son’s primary care physician, and noting that the urine test strip detected signs of hemolysis, we were directed to our local hospital’s emergency room. Because we brought ‘proof’ of prior aHUS diagnosis such as genetic test results and other medical documents, time and efforts moved past “What have we got here?” to “What are we going to do for treatment?” For several days into relapse care over the holiday week we didn’t spot a familiar face from his aHUS treatment a decade ago, but the new medical professionals our family encountered were outstanding in their response to this relapse. Consider what preparedness and care options might be needed during a variety of different situations you might encounter such as a relapse occurring away from home, an accident which may leave you unable to advocate for yourself, or an unexpected illness that may trigger aHUS activity. Preplanning for relapse scenarios such as this helped position our family with a proactive stance that worked to our benefit in ‘crisis mode’. Build in flexibility to cover the unexpected, with a variety of paths to recover improved health should an aHUS relapse occur.
How did a holiday weekend relapse affect available aHUS treatment options?
Simply put, not all treatment options are available outside of normal business hours. A holiday relapse meant no clinical trial contacts were available, and therapeutic drug access was limited to what could be accessed during the weekend. During this relapse period, my mind kept wandering back to how patient location impacts and defines which therapeutic options are available to aHUS patients. Most of the world’s nations have few treatment options for aHUS patients. In the USA, there are two formulations of ravulizumab approved to treat aHUS, with 10mg/mL originally and a later version that was a 100mg/mL formulation approved in Oct 2020. Drug access is not only dependent on national policy, but also on whether your local hospital has reviewed the drug and determined whether to include it within its formulary as a covered drug available for physicians to employ in that specific facility. I hadn’t realized that each clinic or hospital has a review process or board to determine which drugs to include in its formulary, but rather mistakenly assumed that every FDA drug was available for use by medical staff. Shipping during a holiday, weekend, or throughout this winter’s pandemic could be problematic for any product but I hadn’t considered that either.
If you have interest in an aHUS drug candidate that’s currently in clinical trial, best to plan ahead since there seem to be no provisions for ‘after hours’ contact points (Currently there are 28 CTs listed for aHUS with 423 for TMA as of Feb 2021. FMI see Table 1 of the 2020 aHUS Alliance Therapeutic Drug Overview). Limited access to clinical trial leaders -that’s a bit puzzling. Pharma and drug development teams should consider remedies for that – no wonder aHUS clinical trial enrollment is difficult. People newly presenting with atypical HUS are ‘treatment naive’, yet how are their physicians supposed to contact clinical trial groups when office visits are tightly scheduled during the same weekday 9 to 5 business hours open for contact with clinical trial leaders? Needless to say, we were unwilling to delay treatment and let my son’s health deteriorate past his Christmas day relapse, waiting for businesses to fully resume work on Monday 4 January 2021. There went any opportunity to enroll in clinical trials which excluded atypical HUS patients who were not ‘treatment naive’.
What guided your thought process during physician discussions regarding aHUS treatment options during relapse?
From our family’s initial need for aHUS treatment, we began ‘relapse mode’ in the hospital emergency room with documentation of genetic testing and diagnosis. Asked for his medical history, I stated that my son’s prior treatment for aHUS indicated that he was a non-responder to plasma therapies and underwent 13 months of eculizumab infusions. Targeting my comments meant a ‘fast forward’ past diagnosis and inclusion into discussions of treatment plans.
Keeping current with treatment options and with aHUS research was a critical piece for this parent and pediatric caregiver. We were fortunate to have dedicated medical professionals arrange to have eculizumab transferred from a nearby facility to reach our hospital within just a few hours. Given my teen son’s declining medical status, we opted for eculizumab infusions initially and stated in the ER our preference to switch to ravulizumab infusions as soon as labs stabilized and any potential need for dialysis or blood transfusions had passed. I was able to better navigate relapse discussions about relapse treatment with our medical team and with regard to insurance with three specific areas.
1. Cost- Ravulizumab infusions are spaced at every 8 weeks instead of eculizumab infusions every 2 weeks, which aside from ‘quality of life’ impact would mean fewer hospital out-patient infusions with less cost to our insurance company and family finances. Drug cost of both were equivalent, but administered less frequently with ravulizumab.
2. Formulation- The 10 mg/mL original formulation of ravulizumab will be discontinued mid-year 2021 according to Alexion’s 12 Oct 2020 press release regarding the advanced 100mg/mL version with reduced infusion time. There was no logic in moving to 10mg/mL ravulizumab for a couple of months as only the 100mg/mL formulation would be available soon.
3. Ravulizumab SC- We’ll be watching with interest the 3rd quarter 2021 plans mentioned in the Alexion 24 June 2020 investor’s release about its phase 3 study data. If there is indeed a FDA filing plan for a subcutaneous version of ravulizumab, aHUS families would have interest in specific details regarding this proposed weekly pair of self-administered shot/devices administering drug over ten minutes (as noted in the IR).
You’ve mentioned the importance of thinking in advance about the possibility of aHUS relapse and treatment options, but what else might other aHUS families experience during relapse and beyond?
I’m still trying to sort out various issues, and imagine that will continue for some time. My teenage son certainly isn’t a full-grown adult, but neither is he a small child, so which age set of lab value and blood pressure ranges should I use as ‘normal’ parameters? The concept of premedication for his first dose of ravulizumab was discussed then discarded, since that might mask any infusion reaction to this new drug. I’m sure he’ll be fine, but it’s a comforting thought that we’ve got the safeguard of a hospital setting for initial doses of a new drug therapy. Minimum infusion time is clearly noted on the ravulizumab drug info sheets, but I wondered if/how my son’s patient profile (age & size, kidney function, lab values) might affect the infusion rate. While questions might pop into your mind and heart, know that it’s up to you to move such ideas or concerns from an emotional state (concern or worry) into knowledge-based decisions that have the best likelihood to improve health.
Be prepared. Keep learning. Ask questions. Engage in discussion with your medical team, and know the ‘why’ behind aHUS relapse treatment plans. Realize that while living with atypical HUS includes relapse awareness and self-monitoring, your family can choose to focus on how best to live happy and productive lives.The ‘art and science of medicine’ sometimes makes us long for clear-cut answers, and frankly that’s not going to be the case with atypical HUS. Every case of atypical HUS is different, and is ever changing – hopefully to include long breaks in aHUS activity and avoidance of relapse. No one has limitless emotional reserve or energy, which is why aHUS caregivers may try to avoid ‘falling apart’ and instead focus on action steps. Take care of yourself. At the end of the day, families challenged by an aHUS relapse need to find balance in mental health, lifestyle, and physical health.
Have faith, but make your own luck. Perhaps you too will find that the most dedicated and effective ‘Helping Hand’ is to be found at the end of your own arm.
This is the second of a three-part series: Atypical HUS Relapse – A Family View
Fortune Favors the Prepared (Part One)
Expect the Unexpected (Part Two)