People with atypical HUS need urgent care during periods of disease activity, with treatment when needed for as long as needed. But how is such optimal care duration determined, and by whom? Given that this very rare disease affects aHUS patients with highly different presentations, to include kidney damage and potential impact on function of different organs, what guideline exists for patient monitoring? What about patient surveillance when treatment is discontinued, and the concern moves more to risk of aHUS relapse?
Our 1st brush with aHUS: Physician-directed Patient Monitoring
As with most situations involving atypical HUS, my family had more questions than answers. Being prepared for an relapse by creating our own personalized ‘aHUS Notebook’, to include aHUS medical history and genetic test results, to handle an aHUS helped ease our family’s experience a few months ago (See aHUS Relapse, Fortune Favors the Prepared). After more than a decade without any apparent atypical HUS activity, here we found ourselves again with a full-blown aHUS relapse. Patient monitoring was pretty simple and handled by medical personnel, but it was up to our family to know a bit of background information so we could understand whether our son was improving and at what rate. And yes, our family did monitor whether certain labs trended up or down, especially for indicators of kidney function and disease activity, namely blood cell counts (such as red blood cells and platelets) as well as creatinine, LDH, and others noted on the aHUS Clinical Tracker. Our experience was much the same as for any other newly diagnosed medical condition, we listened to our medical team and followed their advice.
aHUS Relapse: Team Approach to Patient Monitoring
The difference this time? Information, backed with hard-fought experience from our first time dealing with atypical HUS. During our blissful ‘Holiday Away from aHUS’, we kept pace with advancements in new information. In that dozen years without aHUS treatment, eculizumab (brand name: Soliris) had been approved by the U.S FDA to treat people with atypical HUS. If we hadn’t kept engaged with aHUS global advocacy efforts and information flow, we wouldn’t have known of the Oct 2020 U.S. FDA approval of a new formulation for ravulizumab (brand name: Ultomiris).
Patient monitoring during this aHUS relapse included complement assays for C3 and C4, right at the first sign of trouble. This time it was more of a team approach to patient tests and monitoring, since we brought the genetic screening report and past medical history within our self-made ‘aHUS Care Notebook’ – and this gave the Emergency Room medical team a heads up as to diagnosis and treatment. When atypical HUS recurs, some patients and family caregivers may feel like our family did, “I know just enough to be a danger to myself and others.” Would running a CH50 assay help inform us as to health status, or guide choices in treatment options? What about C5b-9 plasma levels? While familiar with the ‘normal range’ for regularly monitored labs such as hematocrit, LDH, and creatinine, that’s not the case for circulating complement. And what’s the impact (if any) of aHUS genetic mutations and a patient’s complement profile, including whether their disease state is acute or in remission? (See Table 1, Noris et al 2014) For aHUS patients being treated with ravulizumab, if consistency of CH50 test results are less than reliable, then what alternative exists? Cataland et al noted “Results from the CH50 assays inconsistently demonstrated full complement inhibition, with discordance with free C5 levels.” in 2019 but it seems a point to a large degree still left unanswered. With what frequency should certain labs be run?
It’s a hard life lesson, with potentially devastating consequences if you wait for others to ‘take the wheel’ – people must play an active role in their own medical care. (See aHUS Relapse: Expect the Unexpected) If you’re not sure of: facts about the impact of aHUS on your body and what that means for your lifestyle, have no idea why certain lab tests are ordered and whether a change in results are a good or worrisome trend, or countless other aspects – Ask Yourself This. How can you roll with unexpected issues when they arise, and make choices or take actions that offer the best chance for positive changes in health?
Patient Monitoring Once Stabilized: Now What?
Our family stepped up our game this time around, in terms of learning more about the rare disease which has ravaged our family. But with additional information can come a different set of worries. We knew about which labs meant that tiny clots were still clogging small blood vessels around the body and causing damage to organs. We celebrated lab results that showed the kidneys were healing and regaining their ability to remove toxins from the body. But…
We began to understand how much we didn’t know. And how there is lack of consensus on many issues even among clinicians and researchers who have deep experience with aHUS patients and disease management. And we better understood the aHUS arena has differences surrounding the classification of aHUS, in part due to wide variation of nomenclature and to knowledge gaps which remain a puzzle.
After a period of time, with lab results in the normal range and with recovery of kidney function, patients and their families wonder about how much longer to continue drug therapy. What’s the risk of relapse, and what factors go into that risk assessment? Some can be screened with ‘common sense’. Continuation of poor kidney function gives little safety margin if drug withdrawal leads to an aHUS relapse, since already damaged kidneys cannot afford the relapse risk for taking another ‘hit’ and potentially plunging the patient into complete kidney failure. Every case of atypical HUS is unique, so while genetic testing can provide key information, our family’s Factor H mutation went against expectations when no relapse occurred for a dozen years off-treatment. Patient monitoring tends to settle into a routine of aHUS treatment and lab tests at intervals determined by the medical team and dependent on the patient’s health status and lab results. At this point patients and their families are likely to wonder if this treatment/lab draw regimen will be lifelong. Questioning treatment duration and starting discussion of how long to continue may be a conversation begun by patients or their family caregivers, but also equally may arise from the medical team. Patients are people, so it’s understandable medical teams may overlook (or be unaware of) life changes and circumstances which may lead families to consider when the timing is right to discuss treatment withdrawal.
Patient Monitoring: Stopping Treatment & Being Watchful for Relapse
After months of complement inhibition, discussions with our medical team have led to the joint decision to discontinue ravulizumab. There’s not a clear set of guidelines for aHUS patients who discontinue treatment, however. So now what? Once labs have been fine for a while, at what point do you declare a remission from aHUS activity?
In our family’s case, we had early and ongoing discussions about which of the two US FDA approved drugs to use, and under what circumstances would the switch occur (from eculizumab, brand name Soliris to ravulizumab, brand name Ultomiris.) Deciding to withdraw from treatment is a serious consideration, and not to be taken lightly, so it’s more a decision process based on questions, circumstances and thoughtful conversations.
Vague concerns nagged at our thoughts, which really couldn’t have any actual answer and therefore no bearing on whether to stop treatment – so those we had to put aside. There’s no way to identify the relapse culprit or causal factors – to determine what ‘perfect storm’ of circumstances caused aHUS to relapse after a dozen years of no medication and apparent good health. Instead of wasting time and effort on what ifs, we focused on what types of patient monitoring would most likely provide valuable information to assess health and act as early identifiers of possible aHUS relapse. How could we ascertain low-level damage from aHUS activity before it ramps up, and what could we do for home monitoring?
There’s no silver bullet to stop atypical HUS in its tracks, so our post-relapse plan for discontinuing treatment may seem rather dull. It’s not startlingly flashy or extravagant, but it is sensible and was created as a collaborative result of physician-family discussions. We are most grateful for the excellent work of aHUS clinician-researchers and geneticists around the world, as well as national studies in the Netherlands, France, and the UK,which informed and guided creation of my family’s personal monitoring plan below. (See that research HERE, to include the list for Discontinuing Treatment/Relapse).
Discontinuing Treatment: Our Family’s Individualized Monitoring Plan
Every 4 weeks (once monthly)
*Complete Blood Count (CBC) and differential
*Lactate Dehydrogenase (LDH)
*Renal Function Panel
Office Visit: In 3 months (to alsoo include discussion of multiple topics, such as complement assays)
*1st morning urine, tested Weekly. Call if urine dip test strip indicates blood in the urine.
*Blood pressure, monthly. Record. Parameters, call the medical team if the readings are consistently above a specified range.
Withholding Treatment: as long as labs remain stable.
One might suspect that most atypical HUS patients and their families will likely move through similar stages of patient experience:
Step 1: During an urgent need for treatment. Everything seems a blur, but how to track patient health seems to be mostly mandated with specific labs drawn at particular intervals.
Step 2: Treatment options reviewed with a care plan set in place. Patient monitoring seems mostly clear, but dependent on lack of patient issues such as variations in blood pressure/urine color or output/GI complaints/fatigue. More pressing issues such as seizure activity may result in different actions, but most patient monitoring seems to be reporting abnormalities with results being physician-directed adjustments to medication, an extra set of labs, or an office visit.
Step 3: Settling into a routine, with treatment and lab tests at regular intervals. Mostly physician-driven, with patients/caregivers taking an increased role in watching for & reporting any variations in health status or symptoms. When labs are stable, and patients experience a sense of wellness and/or return to their normal lifestyle, aHUS families wonder about the duration of treatment.
Step 4: Most people don’t take headache medicine when their symptoms resolve, so it’s not a far leap to understand why aHUS families question the need for continued treatment once labs values have improved to the normal range. At what point does the impact of expensive IV drug infusions and potential increased risk for meningitis counteract our fears that aHUS will relapse? Will that relapse risk act as a Sword of Damocles to be forever over our heads, or can we rid ourselves of thinking of the spectre of aHUS as a shadow looming over our lives? We can refuse to let aHUS define us, and instead choose to live with a positive mindset.
Our Notes to this Patient/Family Experience Series on aHUS Relapse:
This article is a single USA family’s actual experience, shared to provide insights and inform discussions. In addition to the unusual aspect of a Factor H patient not relapsing and without any medications for a dozen years following the child’s initial aHUS presentation, this family’s journey included a ‘switch’ from eculizumab to the new formulation of ravulizumab (100mg/mL), then discontinuing ravulizumab after a total of 7 months of treatment with two different complement inhibitors. Since ravulizumab 100mg/mL was approved to treat USA patients with atypical HUS in Oct 2020, we believe it to be the first anecdotal article regarding aHUS patient relapse and treatment discontinuation after therapeutic use of this new formulation of ravulizumab.
Every patient is different, and the aHUS Alliance does not provide medical advice nor endorse medical treatment. Currently there is little data to refer to regarding aHUS patient monitoring protocols for discontinuing treatment, although there are some literature review articles and case studies. Some patients may experience difficulty in quickly obtaining insurance approval to re-start drug therapy once they elect to withdraw from treatment, so patients may benefit from asking that question and requesting clarification and/or specifics. Genetic testing may provide an initial risk assessment based on what is known about the patient’s complement variant and even if there is none, is essential. Prognosis may differ depending on the specific variant with each complement component.
Since atypical HUS is a very complex and rare disease, discussions on appropriate treatment and its duration must center on the individual and their medical team. For a deeper dive into this topic, we invite you to read our article on issues, questions and research regarding the Decision Process: Discontinuing aHUS Treatment. For more insights into the patient experience read the 3 part series aHUS Relapse: a Family View.
Article No. 452
19 August 2021