You have had aHUS. The type of aHUS caused by uncontrolled complement, not the other type. You got access to a complement inhibitor. It WORKED. You tolerated the drug. Your complement is controlled. What happens next%? Stop or not stop is the question?
Some say you must stay on treatment for life because you will get aHUS again if you stop. Some say you can stop treatment and not need a complement inhibitor again.
Who to believe? Who indeed?
Nobody not even doctors/medical specialists can say what will happen to you with certainty. Doctors/Medical specialists say that optimal (most, or best) duration of complement inhibitor treatment is unclear, poorly understood, ill defined, unknown or undetermined. You get the drift. Nothing is guaranteed.
Regulatory guidance recommended or suggested that a complement inhibitor is for life.
Guidance based on two years of clinical study, and which was consistent with previous guidance for treating PNH, which is a different disease to aHUS; certainly, as far as potential remission from disease is concerned.
There is no evidence of long-term necessity as much as there is of what continuous treatment can do in the long term. Years are passing but the long term is still decades away.
Some earlier aHUS patients, before complement inhibitors were around, did go into remission and have not relapsed since. 19 But many patients did not. That is why a more effective treatment was needed. Now it is a matter of for how long is it needed?
You do not want to have aHUS again, well not like you had it before. That is understandable, it leaves you anxious.
On the other hand, if you could be the one who needs no further treatment that would be quality of life changing.
Is it a fifty-fifty chance for you? A mere toss of a coin?
Or is it more or less likely for you.
More likely you will go into a lifetime remission, or would there be a greater chance of you being back to square one knowing that lifelong treatment is for you. Or even a third option that you could go for long periods without treatment and return to it after some respite
What does your doctor/medical specialist have to say about it and what does your doctor/medical specialist know?
Increasingly aHUS specialists and researchers have been addressing the optimal duration of treatment question in different ways, e.g., prospective clinical trials 1,2,3,4,5,6 retrospective investigations 7,8,9,10 , small case studies11,12 literature searches 13 , updates and commentaries 14,15 and coming up with differing conclusions.
Mostly patients volunteered for this research. Sometimes they were forced to give up treatment like the unfortunate transplant patients in Brazil 11, but their experience has still provided some evidence of what happened to them.
All that research evidence and advice is now out there (some only if you pay for it), growing year by year. It is spread over numerous studies that tell of what happened to other aHUS patients over the past decade or more when they stopped complement inhibitor treatment .
It is not a simple matter to learn from all that evidence, it really isn’t for you or your doctor/medical specialist. How does it relates to you?
It would take many hours over days to find and read it all. If you do read them then caution is recommended. There are contradictions as well as agreements; each study is different in scope, and each has different limitations particularly the small number of patients involved. The optimal duration remains debatable among physicians. There is limited consensus. And you are in the middle of it.
So, what is the most reasonable thing for you to do as things stand?
What would persuade you to move away from your current safe place? Would it be reasonable to stay as you are or not? It is your choice? Do you need treatment or just want it?
| . | Need | Not need |
| Want | Accepted life | Dependent life |
| Not want | Burdened life | Normal life |
To do anything firstly there are things you need to know about yourself and how the process of stopping can be done as safely as possible.
The one issue that there is a consensus on by clinicians is that there are risks to stopping treatment.
The real risk is of a relapse doing more harm to you. Not just the chances of a relapse, that would mean a risk of disappointment. It is the physical harm done that matters. And so those risks need to be known and managed professionally.
The other side of the coin is that full remission from treatment is probable too. Normality can return.
Some might say something like “feel the fear and try it any way” particularly if you can be assured no harm will come to you.
So, what needs to be considered in making a treatment stop/continue decision?
This is the kind of stuff that is spread through all articles about complement inhibitor, withdrawal, discontinuing, stopping, ceasing whatever you want to call it. Mainly about eculizumab but could be applicable to all complement inhibitors in the future.
And the danger is that general assumptions are made about the findings. There is no single factor which can predict with certainty that without treatment a remission or relapse will result. It is more complex than that. There are predictive factors for likely relapse/remission and predictive factors about likely harm.
In no order of importance these are some of the factors identified in studies as predictive of the chance of a relapse or at risk of harm from it .
| Chances of a relapse | Risk of Harm |
| complement genetic variants | going it alone |
| previous TMA relapse episodes | re-initiation delay |
| unclear aHUS diagnosis | enforced unsupported discontinuation |
| any current complement activation | level of residual kidney function after previous episode |
| being female | no clear care safety net |
| young age | |
| exposure to triggering conditions | |
| previous dialysis experience | |
| History of extra renal manifestation | |
| family history of aHUS |
And researchers are still looking for additional predictive factors and greater precision on their probabilities. 18
Remember it is also a case of whether and how these factors apply to you and what their predictive value is.
Researchers have pinpointed these risk factors in their studies but they do not necessarily all agree on their relevance or impact.
The collective findings usually show that after stopping treatment some of those with high levels of risk will still need a complement inhibitor. But not all.
Also found was that most with low levels of risk factors are very likely to no longer need a complement inhibitor when they stop treatment. But not all.
The real risk is that for those who find out they do need it after discontinuing treatment that they are not harmed in the process of trying.
There is consensus on the need for a robust safety net to catch those relapsing and put them back on treatment rapidly.
Ideally within 24 hours of signs of relapse as researchers have found that such a rapid return pathway invariably results in no lasting harm being done. 1
One day you may be in a room with your doctor/ medical specialist to discuss discontinuing complement inhibitor treatment . It would be helpful for that discussion for you to know where you stand on the matter so that your decision is seen as sensible and reasonable whichever way you decide to go.
Try it or not.
“Not” is the default and safe position for now but you could be persuaded by positive evidence and if there’s safe way to do it, so you are not harmed by a relapse. If evidence is not positive and/or there is no safety net, saying “ No” is a valid stance. You are informed.
aHUS alliance Global Action has given this matter a lot of thought as we are people who are as much affected by this decision as anyone else is in the community.
In the absence of there being nothing available which looks at this dilemma from a patient’s perspective we are proposing a Patient’s Own Risk Evaluation for Treatment Discontinuation Model which helps a patient see where they stand, and what, if anything, is missing to arrive at a reasonable personal stance on the matter one way or the other.
If you are now ready to look at the model, follow this link to the next article.
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