Article No. 422
4 March 2021
There’s an old saying, “When you get to the end of your rope, tie a knot and hang on”. I wouldn’t be surprised to learn that the unknown author of that adage had experienced living with a rare disease. After a decade without aHUS activity, my family closed out the year 2020 with the bang of a full-blown atypical HUS relapse. Having prior experience with the challenges caused by this very rare disease, we found there to be some differences in initial diagnosis and treatment versus having a recurrence of atypical HUS activity. What remains the same is the interwoven threads that bind us together, that join to create a stronger response in the face of adversity, that unite to pull together toward common goals of improved health and of faith in a better tomorrow.
First steps: Walking back into aHUS activity Concerns about lack of appetite and dark urine prompted use of an at-home urine dip test, yielding a color change indicating a positive reading for erythrocytes (urine containing red blood cells). After calling my teen son’s primary care physician with our suspicions of an aHUS relapse, we followed the doctor’s directions to report to our local hospital’s Emergency Room. Had it not been a weekend with additional closures for a major holiday, there likely would have been an intermediate step of blood draw to provide medical data (a blood count, metabolic panel, and LDH). We brought our family’s self-made ‘aHUS Care Notebook’ to the hospital, which contained various key medical elements of my son’s aHUS medical history. Being prepared with documentation of his aHUS diagnosis, genetic screening results, and treatment records allowed us to immediately move from the status ‘emergency presentation, unknown’. Instead actions proceeded with specific lab orders that would indicate aHUS activity, and followed by immediate discussion of treatment plans to address those abnormal results. (See article one, on Relapse Preparedness)
Mindset Differences No matter how prepared you try to be for the possibility that the genetic predisposition for atypical HUS may launch into aHUS activity, expect the unexpected. Circumstances change. Life is dynamic, so it’s only realistic to take into consideration that new medical providers might oversee your care, research may expand options, people and places may change, pediatric patients grow up, and needs or concerns may vary from previous episodes of atypical HUS.
As situations evolve for yourself and your family, keep learning about both the disease and about what an aHUS relapse may do to your current lifestyle. In the throes of initial aHUS presentation and diagnosis, I had a steep learning curve and felt like I was on an emotional rollercoaster. Ditto with the second time around. With the aHUS relapse, I found I’d forgotten the body’s cycle of cell regeneration and aspect involved with monitoring healing stages of kidney damage. Even as platelet counts increased and red blood cell levels declined, I had to face the next day’s frustrating ‘seesaw effect’ where those numbers reverse or small gains are lost. I’d kept track of advancements in aHUS therapeutics and research, which enabled this family caregiver to participate in discussions regarding treatment plans and disease management. But I’d blissfully forgotten the myriad difficulties with insurance, and the red tape to cut through since aHUS disease management falls outside the normal parameters of common illnesses. Seldom is there a box to ‘tick’ regarding rare diseases like atypical HUS. I’d forgotten that aHUS care doesn’t appear as a flowchart type of approach to decision-making but is better viewed as ‘the art and science of medicine’ with plenty of gray areas. Nuances are important, and events rarely go as one might expect, and I’ll admit to being uncomfortable with that. (See relapse article Part Two.)
Since a diagnosis of aHUS was already documented, how did relapse treatment differ from treatment plans at initial onset?
When my son had his first aHUS episode as a young child, he didn’t respond to any plasma therapies such as infusions or plasmapheresis. He was an early adopter of treatment with eculizumab, and after using it for 13 months eculizumab was discontinued because 10+ years ago hadn’t provide enough time to collect study data regarding any potential impact to children’s development. (Within a year or two, research indicated there was no concern along these lines.) We knew that our son had responded well to eculizumab before, and during relapse we anticipated that same treatment would likely be effective again.
I’d made it a point to learn about atypical HUS over the last decade, and that knowledge was invaluable. Because of the COVID-19 pandemic, most of the emergency room staff was familiar with the term ‘thrombotic microangiopathy’ and knew that TMA clots could damage not just the kidneys but also the lungs and other organs. Not only was medical staff more aware, but I was more informed and thus able to employ key medical terms used in connection with COVID-19 (TMA, complement dysregulation, multi-organ involvement) to better explain why rapid treatment of aHUS is important.
Keeping pace with medical advances and aHUS research meant that I had some background information about drug candidates in clinical trials, and which two drugs which were FDA-approved in my nation (USA). This time I could ask informed questions, provide medical staff printed materials about aHUS, and hold my own as a contributing member of my son’s care team. While I’d already thought carefully about our preferences for aHUS treatment during a relapse, I didn’t anticipate that treatment options would be limited due to the timing of his relapse.
What kinds of questions occur to you in dealing with a relapse, that seem different from those that arose during diagnosis?
Will the ‘recovery time’ be similar to the initial episode of aHUS activity? During relapse, does the body “recognize” a complement inhibitor if it was a therapeutic drug given during prior aHUS episodes? What about the recovery process from kidney damage caused by aHUS relapse, in what ways might it be different from the initial episode (such as slower healing process, more scarring, different outcome rates for eGFR.)
Do ‘treatment naive’ patients experience adverse events (AEs) at the same rate as patients who have had prior complement therapies? Or are there fewer(or less severe) AEs or less severe for patients previously treatment with complement blockers?
Shouldn’t there be more informational materials for aHUS patients to present at Emergency Room visits, on the topic of physician assistance and education? Materials on these topics would lessen the burden on patient/caregiver explanations and allow focus on key medical aspects to include: How to Distinguish aHUS from other syndromes of TMA, aHUS Diagnosis & Treatment, Think aHUS if a Family History includes Kidney Disease, Multi-Organ Involvement in aHUS, and Plasmatherapy: Types & Limitations.
Why isn’t there more ready access to physicians and patients wishing to know more about aHUS clinical trials? Shouldn’t there be an ‘after hours’ urgent care contact point on all press releases and postings about clinical trials? Given the high interest of aHUS patients to participate in aHUS research (2016 aHUS Global Poll) where are the disconnects in information flow, enrollment, and patient engagement efforts?
What differences exist (if any) for monitoring patients during an aHUS relapse? Does the type of complement inhibitor affect patient monitoring protocols? Do the ‘return to care’ pathways differ, and if so, in what ways? Is there a difference in patient surveillance for those using eculizumab versus ravulizumab? What about the different interpretations and limitations of CH50 to assess degree of complement blockade in patients receiving ravulizumab (Cataland et al, 2019). As remission studies continue to expand and inform prognosis of treatment withdrawal, what will emerge as precise key predictors of relapse?
Less than one-third of aHUS patients around the world have access to ravulizumab or eculizumab. Why aren’t physician organizations supporting such increased access through collaborative global aHUS review panel, such as the model by South Africa’s Prof. Mignon McCulloch and Dr Errol Gottlich? How can aHUS families team within their nation with physicians, research teams, and rare/renal/genetic organizations to address health care policy in their country? What’s happening with development of new aHUS drugs, particularly those other than complement inhibitors, with either oral (pill) or subcutaneous (shot) delivery that might offer improved quality of life for patients? What effect might less expensive drugs such small molecule drugs or biosimilars have on treatment options for aHUS patients in low resource nations?
How do you know these things, and what advice do you have for aHUS patients and their families?
Everyone gets to choose what matters in their life, and often that’s evident in their actions. My personal choice is to be prepared and flexible, in order to respond proactively to whatever life throws my way. Even if it’s my teen’s recurrence of aHUS. Being able to accept circumstances and adapt to them means that before this relapse I’d kept current with aHUS research and medical advancements. My son was already enrolled with Alexion’s OneSource program. We’d participated in aHUS global advocacy as well as research and studies, such as the longitudinal aHUS study at the U of Iowa’s MORL genetics lab. It’s not in the least remarkable that people would be attentive to something that might impact the future or daily life of a loved one. Striving to be both caring and knowledgeable are fine personal goals, even if I sometimes fall short. I’ve shared information with other atypical HUS families by volunteering with the aHUS Alliance Global Action team – joining efforts with others who are aHUS adult patients or family caregivers. News and information important to aHUS families is posted on the aHUS Alliance website, social media such as Facebook and Twitter, the Atypical HUS Resources page, and in the issues of aHUS Global Advocate newsletter.
Patients and caregivers, working with physicians and researchers, are the everyday heroes at the core of medical advancements. Just as a rope is formed of individual threads woven together, it takes many different skills and talents to combine and carry the burden of aHUS. The tensile strength of a rope, during an aHUS relapse, can be expected to break if you remain a single thread unconnected with information, people, and aHUS advocacy efforts. Every nation with multiple aHUS treatment options has those policies in place because aHUS families before you paved the way, working together with other people and groups to advocate for better patient outcomes. The aHUS Alliance can help you get started, with their R.O.W program, or with advice on how to become an aHUS advocate. Maybe you’ll gain insight into how aHUS families have worked to change drug policy in their nation, like the journey of the UK’s Reluctant Advocate. Share in challenges and goals that link us, join with collaborative efforts that aim to build a better future for those living with atypical HUS. Blessed be the Ties that Bind.
This is the last of a three-part series: Atypical HUS Relapse – A Family View
Fortune Favors the Prepared (Part One)
aHUS Relapse – Expect the Unexpected (Part Two)
The Ties that Bind (Part Three, this final article in our aHUS Relapse Series)