Article No. 400
5 December 2020
The research undertaken by a group from John Hopkins University Hospital took a different approach. Theirs was a retrospective look at what happened to 32 aHUS patients consecutively enrolled in their Complement Associated Disease Registry between January 2014 and December 2019 who had received eculizumab treatment.
An abstract from the article can be read by clicking on the title below.
7 remained on that treatment at the end of the period and 25 had discontinued treatment. Of the 25 withdrawn ,5 patients relapsed ( 20%) relapsed. Another relapse rate in the 20% to 30% range.
The median age of the patients was 44 years and 78% of them were female. 59% of those who been tested for complement variants were found to have significant variants. The patients had been receiving treatment for an average of 2.37 months.
18 (72%) of the 25 withdrew under medical direction ,7 chose to do so themselves through non-compliance with treatment. Their reasons for doing so are not reported.
The non -compliant “withdrawals” had the higher relapse rate of 42.8% and 1 patient died. The clinician controlled group of patients had a relapse rate of 11%.
The 4 surviving relapse patients returned to eculizumab treatment and recovered renal function to pre-withdrawal levels, or better . 9 out of the 25 withdrawal patients saw their kidney function improve at follow up compared with the level at time of withdrawal, and 15 remained stable.
As withdrawal on average was less than six months from initiating treatment, it would be expected that more kidney function would be regained at six moths or longer. It would appear this additional recovery can happen even without eculizumab.
The research group inevitably saw self-withdrawal through treatment non-compliance as the most significant cause of relapse. The group did not see having a genetic variant as significant , only 40 % of those with test results had CFH or MCP/CD46 mutations.
11% had not been tested. Such data is needed for patients to make an informed choice.
This research group also concluded that , for the majority (70 to 80%) of aHUS patients, withdrawal from eculizumab treatment with close monitoring is safe to do.
What has aHUS Global Action learned from the research featured in the past few days is:
-for the majority of patients treatment withdrawal is successful;
-although not yet complete, data exists to make an informed decision by clinician and patient;
-patient understanding and attitude to risk is important;
– complement genetic variant knowledge is important, not just knowing which component is defective component but knowing the way in which it is defective
– not having a genetic mutation increases the chances of no relapse remission;
– patient characteristics like gender and age can influence relapse, but children can successfully discontinue treatment;
– treatment 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 treatment should be considered not less than six months after initiation and not whilst C5a-9 remains active;
– close monitoring from the time of withdrawal is needed to ensure the process is safe.
From its original prescription eculizumab was considered to be a life long treatment for aHUS as it was for PNH. But subsequent research has altered that view on what the optimal period of need for treatment is.
Alexion acknowledges in its prescription advice for ravulizumab for treatment it may not always be life long.
It says ” In aHUS, ravulizumab treatment to resolve thrombotic microangiopathy (TMA) manifestations should be for a minimum duration of 6 months, beyond which length of treatment needs to be considered for each patient individually”
Some time should be taken whilst on treatment to research the findings in articles like those featured these past few days to determine whether a patient matches and would be considered a candidate for a highly likely successful discontinuation of treatment.
Knowledge is power as is said and each patient should inform themselves for making such a decision. Each patient needs to know what they specifically need to know.
And that would include any safety monitoring processes which will be in place, certainly in the immediate period in the months following withdrawal, along with a guaranteed pathway to return to treatment if relapse is experienced.
The aHUS Patients’ Research Agenda asked the question…
3.4 Can a complement inhibitor be stopped safely when not needed by some aHUS patients and what makes them different?
The answers emerging are “yes!” and “there are differences which have been observed which can be used to predict what may happen if treatment is discontinued”
Such answers need to be heeded.