Article No. 457
Yet another article about the outcome of withdrawal of eculizumab treatment has appeared. It is not about a controlled trial of patients selected to test withdrawal of treatment. This one is based on what was observed by the Alexion aHUS Registry, ( Full article can be seen HERE ). It is possible that some of the patients observed may have participated in national treatment withdrawal trials too.
Within the Registry there are aHUS patients who have withdrawn from eculizumab treatment by their doctors. The Registry investigators looked at what happened to 151 such aHUS patients who had been successfully treated with eculizumab. 118 had no TMA relapse after withdrawal at the time of publication.
Of the 33 who did relapse the investigators found that
1- they had a history of extra renal manifestations prior to treatment ;
2- pathogenic variants ( mutations)
3-family history of HUS
All of which adds to the risk analysis considerations required prior to an informed decision to successfully withdraw from treatment. Global Action are not aware of items 1 and 3. being cited before, whereas there is already more detailed information about item 2.
There were several reports on eculizumab withdrawal published late last year along, with case studies, so the time is coming when all this current insight should be brought together in something that can be used by any treating clinician anywhere to talk to their aHUS patient about.
It is as important to use such evidence to explain to patients why treatment is not going to be withdrawn as it is to counsel those patients who are most likely no longer needing treatment and would be able to have that burden lifted.
It is particularly important for those who when all things are considered are at the margin of such a decision,
For the latter, it is very important that the monitoring process following withdrawal is safe, sustainable and proportional over time; reflecting best practice.
Any such consensus advice will of course need updating as more is known about known predictors and probabilities.
Indeed there may be other predictors not yet found e.g whether higher levels of ADAMTS13 at first presentation, which might predict plasma exchange treatment success and withdrawal, might be a predictor of complement inhibitor withdrawal too.
In fact could anything be learned from all those patients who have gone into remission, whether or not they have been treated by eculizumab. What is it about them?
So whilst there is no longer a paucity of information, what there is has not been suitably collated to inform aHUS patients.
There is growing evidence that withdrawal of eculizumab ( and thus ravulizumab) treatment for aHUS can be successful. It is no longer regarded as a life time treatment for all. Though it will be for some. Withdrawal can lead to relapse. Sometimes that could have been predicted. Some times it might reveal another factor which adds to the “risk assessment matrix”.
The French “StopECU” study intends to produce an algorithm which can predict a withdrawal outcome. It is needed very much.
The aHUS Patient Research Agenda topic question is “Can a complement inhibitor be stopped safely when not needed by some aHUS patients and what makes them different?“
The answer is “YES” and more is being discovered on when and why it may not be needed because of the differences in aHUS patients, and how to do it safely.
Done safely based on evidence that a patient is suitable to withdraw, and is also part of the decision making to release them from a treatment burden with more assurance.
Health policy makers who are put off by the cost of eculizumab treatment today, could be persuaded that collectively aHUS patient complement inhibitor treatment in their country would be more cost effective than has previously been thought.
So more patients, currently denied treatment, could benefit.
Consensus will make that possible.
……………………………..
As can be seen from the list of previous articles on treatment withdrawal aHUS alliance Global Action is fulfilling its duty to inform on this important aspect of living with aHUS.
ECULIZUMAB WITHDRAWAL- SAFE AND REASONABLE?
…using the above link. Although the title suggests this is about withdrawal of treatment, withdrawal in this case includes those patients who have had their doses tapered i.e given lower…
WITHDRAWAL EVIDENCE PATIENTS NEED TO KNOW
…withdrawal should not attempted through non-compliance – withdrawal should be discussed with clinicians -kidney function can still improve or at least remain the same for those who relapse –withdrawal from…
ECULIZUMAB WITHDRAWAL RISK PROFILING
…withdrawal from eculizumab treatment. RISK OF WITHDRAWAL OF ECULIZUMAB In the current aHUS related trials list reported on recently, there were two which were looking at the safe withdrawal of…
RISK OF WITHDRAWAL OF ECULIZUMAB
In the current aHUS related trials list reported on recently, there were two which were looking at the safe withdrawal of eculizumab. In addition to these two trials, it is…
DECISION PROCESS: DISCONTINUING AHUS TREATMENT
…Eculizumab: On Treatment Withdrawal Evidence Helps Eculizumab Access Eculizumab Withdrawal – Safe & Reasonable? Eculizumab Withdrawal Risk Profiling (Acosta Medina Group, re TMA at ASH20) StopEcu: The French Study Reports…
REMISSION FROM AHUS
…withdrawal will be captured by these important studies. Many other patients are going through withdrawal, but the knowledge of how they fared may be lost to the aHUS community and…
ATYPICAL HUS – RESOURCES
…to Treatment 2018 aHUS Therapeutic Drugs, Market Factors Stopping Eculizumab: On Treatment Withdrawal Decision Process: Discontinuing aHUS Treatment Evidence Helps Eculizumab Access Eculizumab Withdrawal – Safe & Reasonable? Eculizumab…
SPOTLIGHT ON RAVULIZUMAB 4- SIDE EFFECTS
…when needed for as long as is needed( Minimum 6 months) . It is not for life for everyone but neither is withdrawal for everyone. This is a significant change…
ACCESS TO ECULIZUMAB
…guidelines, eculizumab withdrawal and interval extension protocols Continent Country Are there national aHUS treatment guidelines? Is there a national controlled ecu withdrawal process? Are patients included in withdrawal decision? Is…
AHUS- WHEN PEX IS A SUCCESS
…go into remission different to those who cannot? This has been expressed in the Global aHUS Patients Research Agenda. As more and more patients attempt a safe withdrawal from eculizumab…
ATYPICAL HUS IN THE NETHERLANDS
…additional information if withdrawal after 3 months is equal to withdrawal after 6 months (like the STOPECU trial for example). How will the CUREiHUS study fit into a…
ASN, AHUS AND THE SISTERS FROM MISSOURI
…for safe withdrawal too. The conference programme also had a talk by Dr Romy N Boumeester and posters featuring the researchers from Radbourd Medical Centre Nijmegen about withdrawal and personalised…
CAN ECULIZUMAB BE STOPPED?
…its first meeting in Barcelona, the alliance heard from the patient organisation in Italy about the work that had begun on eculizumab dosage adjustment and withdrawal on some Italian patients…
SPOTLIGHT ON AHUS RESEARCH – JULY 2021
…reflect information now available on studies into stopping treatment, optimal treatment duration, and risk of aHUS relapse with treatment withdrawal. We’d like to highlight here a few recent additions…
AHUS TRIALS WATCH 8
…is an eculizumab withdrawal “PLUS” study and could lead to a novel strategy for withdrawal from eculizumab ( and ravulizumab?) for those with a high risk of recurrence. The clinical…
AHUS TRIALS WATCH 5
An update on STOPECU ( NCT02574403) -the French Study of the withdrawal from eculizumab treatment which began in late 2015. ( click here for trial details ) and has planned…
SPOTLIGHT ON RAVULIZUMAB 1- DOSING
…patient needs Ravulizumab, but the alliance hopes that such decisions about withdrawal from Ravulizumab treatment should not only be based on the current evidence about safe withdrawal, but also should…
WHAT BECAME OF THE AHUS 130?
…the 21 returned to eculizumab treatment because of recurrent TMA. Five returned to treatment when they had a kidney transplant; four either missed a single treatment or their withdrawal was…
EVIDENCE IS POWERFUL AND PERSUASIVE
…and sustainable eculizumab dosing and withdrawal strategies. As a result the Health Authority Committee liked what they heard and agreed to a Study taking place with full patient participation. The…
AN AHUS RESEARCH AGENDA CASE STUDY
…harmful to the foetus, if so whether a temporary withdrawal from eculizumab was advisable given the risks of recurrence, even if in remission. The patient has had a history of…
MILAN -THE FINAL STOP BUT NOT THE FULL STOP
…renal conferences. Perhaps Centro SEU is best known for the pioneering work over the past seven years on the withdrawal of patients from eculizumab treatment as well as the tailoring…
AHUS RELAPSE EPILOGUE: PATIENT MONITORING
…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…
ARE CHINESE AHUS PATIENTS DIFFERENT?
…transplants and complement inhibitor withdrawal. As all cases were reported as sporadic i.e. non familial, it is unlikely that any aHUS patient of Chinese descent elsewhere in the world will…
“STOPECU” – THE FRENCH STUDY REPORTS
…female and having a genetic mutation more likely predicts a relapse. But having previously been on dialysis does not. Those who had active C5a-9 at the time of withdrawal contributed…
EVIDENCE HELPS AHUS ECULIZUMAB ACCESS
…medicine remains available. The results are of no surprise to anyone who has been been following several eculizumab withdrawal and tapering studies around the world over the past eight years….
THE EPILOGUE
…study of the safe withdrawal of eculizumab , a NICE condition to its approval and which underpinned that part of aHUSUK’s vision for eculizumab that it should not only available…
BEFORE OR AFTER , WITH OR WITHOUT- TRANSPLANT DECISIONS NEED DATA
…and identify any returning TMA activity at the earliest opportunity. But the answer to those questions should be part of what is found out about withdrawal from eculizumab studies going…
FROM AHUS CONFERENCE ATTENDEE TO PRESENTER
…on pregnancy and transplant.Further talks would be about withdrawal from treatment research , patient registries and research fundraising which would add to the topicality and planned research fundraising programme that…
CLOSING THE AHUS KNOWLEDGE GAP A BIT MORE
…of disease duration.” Click here for full abstract Is it possible to ensure the effectiveness of eculizumab in the body? Kioa L Wijnsma’s group looked at withdrawal of eculizumab when…
AHUS AND COVID-19
…the point about the withdrawal from eculizumab treatment patients and their self monitoring. They have a direct pathway to a return to eculizumab if needed. Sepsis is one of the…
RAVULIZUMAB COSTS LESS OVER A LIFE TIME
…treatment. Its views on the possibility of withdrawal therefore remain very conservative (they assume only 45% of those with chronic kidney disease levels to 3 ,who represent about 11% of…
RARE DISEASE DAY VIDEO 2017 REPRISE
…from aHUS onset Rebecca of Fort Worth USA also raised this issue Withdrawal from aHUS treatment Research and education with aHUS Secondary aHUS diagnosis Recovering from aHUS Affordable care…
AHUS RARE DISEASE DAY 2018 COHORT – REPORT 2
…the better the prognosis and management of the disease , including transplant and withdrawal from eculizumab decisions. Tested Not tested Total 97 6 103 94.5% 5.5% 100% Of those receiving…
AHUS KIDNEY TRANSPLANT-MORE INSIGHTS
…to speed up access to eculizumab if needed Rescue eculizumab is needed quickly ,5 days or sooner from onset, to get best outcomes Withdrawal of eculizumab for those with transplants…
AHUS IN PREGNANCY AND AFTER
…treatment algorythm. This included eculizumab for aHUS, and also when it could be withdrawn. Withdrawal is possible but when that happens depends on the characteristics of patients. Pregnancy is not…
AHUS GROUP EXPECTATIONS FOR 2018 (CONTINUED)
…will establish a risk management approach to the withdrawal decision. Participants in the Study will have the opportunity for their views on the experience to be recorded in a parallel…
SOME SIDE EFFECT- MENINGOCOCCAL INFECTION!
…of aHUS patients with meningococcal infection has better outcomes than someone from the general population. vigilance needs to be continued for a time after withdrawal from eculizumab treatment; carry the…
AHUS RELAPSE: THE TIES THAT BIND
…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…
“AWAY FROM HOME” ECULIZUMAB INFUSIONS
…to those who are being routinely treated with eculizumab, and even those who are in the process of withdrawal from eculizumab and in remission. The first two basic facts about…
