Being An aHUS Trialist

Article No.  419

16 February 2021

It is spring time in 2017. You feel very unwell, very poorly. It is thought you have aHUS. You get a chance to have a new treatment for aHUS. It is called  Ravulizumab. You can get as part of a trial. You are accepted and get the first dose, There are 57 more patients who are in the trial.

By the second dose, 2 of the other 57 have dropped out. They have not got aHUS, They are found to have e.coli and so have HUS, not aHUS.

There are still 25 weeks to go of the 26 weeks that the trial is to run for. You do not know who the others in the trial are. If you were all in one room about half of you would be overs 40 years of age old( the oldest in their 77th year) and half are younger than 40 (the youngest being just 19 years old). Two out of three of you would be female. Just over half of you would be white. Eight will have had a kidney transplant and eight  will have just given birth before their aHUS onset.

You are still on the drug as the dosage moves to 8 week intervals. How will you know if it has worked for  you? Trial investigators will deem it to have worked for you if you reach some stringent stated outcomes. The primary outcome being when you have a complete TMA response. You will have complete TMA response when three measures of things in your blood reach the targets they set.

Firstly your platelets ( these are involved in blood clotting)  will have to be back in the normal level range, Then your lactate dehydrongenose or LDH  ( appears in blood when cells are damaged)  is back to normal levels again. Finally you creatinine ( produced in the blood when kidneys are not working properly or at all) will have reduced by more 25% of the level it was when you entered the trial. And all of these need to happen before, or by, 26 weeks, or 183 days.

By 183 days, you are one of 41 aHUS patient who have normal level of platelets , or one of  43 who have normal levels of LDH, and  you are one of 33 whose creatinine has reduced by more than 25%.

For how many has ravulizumab achieved all three for?


But by 26 weeks there are only 49 patients still participating in the trial.  Another seven have dropped out along the way for different reasons, Two, sadly, have died for non-treatment reasons.

So for just under two thirds of those left in the trial, ravulizumab has done its job. For some it did the job in just over a week, For half in just over a month.That is how quick clinical recovery can be with a complement inhibitor.

Platelets return to normal showing  excessive clotting is stopping, then LDH ( which shows that the linings of blood vessels/capilliaries are recovering)  and finally, in a little more time, some renal function returns.

Ravulizumab is not repairing these, it is natural processes which are doing that, But ravulizumab has stopped a part of your Complement system, C5, doing any new damage, giving your body time for the old damage to be repaired.

Complete TMA response  was the intended primary outcome of the trial, Trial investigators had a longer list of secondary outcomes. Including how many patients came off dialysis treatment ( 40 of you will have reached Stage 5 kidney failure); as well as quality of life measures and measures of  fatigue felt by  patients Taken together these may indicate how better patients feel.

How patients fared with all those can be read in the trial report in the  Clinical Trials database CLICK HERE.

The results can also be seen in an article, written by a group led by Dr Eric Rondeau and which has been presented at conferences during 2020. This article can been by CLICKING HERE.

It is now nearly four years since the trial begun and it was intended that patients in the trials  would be followed up for five years. At some point it will be revealed what happened to patients after the initial six months period  up to the end of follow up.

However, an article about a sub-group of those in the trial was published last month. Specific information has been released about the group of women entering the trial after they onset with aHUS shortly after giving birth. Remember there were 8* of them. 7 of them achieved a complete TMA response in 31.5 days.The article about the study by, Anja Gackler and her group, can be read by CLICKING HERE.

aHUS patients and others who enter aHUS trials like this  are helping other patients in the global aHUS community. It may be that, as in this trial, they can get access to a new treatment, which they may not have been able to access. It may be their last hope.

There will be other such trials and the chances are there are people today,who have no idea that they are susceptible to aHUS, will find, when it hits them, their lives will be saved because of new aHUS treatment development. Hopefully these will include those who need affordable treatments right now but have no access. It will give them a chance.

It is human nature to think that having to rely on regular treatment is a burden. But with each new development it becomes less of a burden for aHUS patients, who not so long ago faced so much worse.

Now it is about how soon recovery from an episode can be achieved for most and when even the treatment that brought about the recovery is no longer needed for now.