USA aHUS Patients-2000 or more and rising?

Article No.  362

27 July 2020

Ask Google ” how many aHUS patients are there in the USA?” and you will not get an exact answer. Understandable really,  as there are no records which can be used to give an answer. There is not even a health classification code for aHUS , only for “HUS” and “TMA”. So hospital records are of little help, without a lot of work.

Even if  there were such records, the numbers would be changing from day to day,  all the time.

The question is actually seeking the “prevalence ” of  aHUS in the USA i.e. those surviving at any point in time.  Over time some patients die, and each year new patients experience the illness, the latter being the “incidence” of aHUS.  The terms incidence and prevalence are not interchangeable but sometimes are in literature and become confusing to those seeking answers.
Ask “what is the prevalence of aHUS in the USA?” ,and the answer given would be “between 1 and 2 cases per million in the population“. Those are the aHUS prevalence rates that have been used for many years to estimate the number of aHUS patients in the USA.

As the USA population continues to increase the aHUS patient numbers would increase. So USA aHUS patients would have increased  from between 321 and 642 in 2017 when the population was 321 million, to between 329 and 658 in 2019  when the population rose to 329 million. An increase of between 8 and 16 patients over that time.

The prevalent numbers  will already be higher in 2020.

But how correct are these estimates, are they even in the right ballpark?

To the author the numbers look far too low. Three years ago Global Action said in answer to a question about aHUS prevalence asked in the Rare Disease Day video, that there would be  somewhere between 600 and 1800 USA aHUS patients assuming a prevalence rate of between 2 and 5.5 patients per million. But even the prevalence rate of 5.5 per million used in Europe at that time may now be dated.

A recent piece of USA research which featured on Global Action’s website ( Article No. 360 here ) provided some information about actual patient numbers treated with eculizumab in some USA hospitals between late 2011 and early 2016. In the USA’s Premier Perspective Hospital Database,  the researchers found a prevalent eculizumab treated population of 222 aHUS patients.
It was claimed that this patient database held records of 20% of all USA patient hospitalisations.

Making a not unreasonable assumption that this actual number  was  representative of any databases for the other 80% of USA patients in that period then by multiplying by 5 , it is possible that were 1110 prevalent aHUS patients in the USA by March 2016.
Well at least those aHUS patients who would have been receiving eculizumab treatment. Only Alexion can say whether that was the case or not based on their sales knowledge.

That prevalent number would have built up over  a 4.5 year period  at an incidence of  about 250 treated patients per year. If that treatment incidence  level continued in the following four years until March 2020 ,  another 1000 eculizumab treated patients could be added.
The  prevalent USA  aHUS  population in 2020 would be at least 2110 patients.

It could be argued that the average 250 per year Eculizumab treatment incidence between 2011 and 2016 understates the incident rate in the later years because there would have been a gradual build of usage and sales of what would have been a novel treatment in 2011.

Even assuming that the annual incident  rate by 2016 was only 20% more than the average incident rate  for the four and half years , that growth would add 200 more patients to the estimated prevalence in 2020. Increasing the minimum prevalent population to 2310.

But there are other aHUS patients who may not be included in the hospitalised with eculizumab treatment data in that period. Some patients were excluded from the 222 figure and no aHUS patients not treated with eculizumab were included.
Firstly there are those who were on the aHUS eculizumab trials prior to 2011. Another  100 patients could be added for those say.

Then there are those who would have gone into remission without eculizumab treatment. Prior to 2011  30% of all incident patients may have responded to plasma exchange, for example, and survived, although little is known about happened to them.After 2011 some of those patients would be more likely to be in the eculizumab treated cohort, even if they withdrew  from treatment later.
The post eculizumab era patients  who might go into remission without eculizimab  would probably be less , say 10% of all treated incident patients i.e. 30 per year for 8+  years , or about  250 in total. Add to that 30 % of incident patients for the 5 years before 2011,  roughly 450 patients say, who remain in remission to this day.

At any time there will be aHUS patients on dialysis awaiting a transplant. Although  their prevalence should be reducing each year as  new aHUS onsets are successfully treated and so patients are not going into end stage kidney failure. Furthermore dialysis patients should be having eculizumab supported kidney transplants.

There will be some who will never have a transplant, although no one really knows about how many such aHUS patients there  are  who  are effectively “left behind”. There could be around 150 or so dialysis patients in ,or out of, the USA kidney transplant queue.

Finally some of the 222 eculizumab treated aHUS  patients have died . There were  21  out of the 222, at about 5 a year on average.  So out of 1110 total treated patients there could possibly have been about 105 deaths. At around 25 per year between 2011 and 2016 and perhaps another 100 up to 2020 . In total  205 aHUS patients could have died.

Table 1 brings together the estimated numbers in each of the cohorts discussed above. Figures are also included based on an assumption that the 222 “actual”  aHUS patients in the database represented 50%,  not 20% , of all USA aHUS patients hospitalised in that period.

Table 1 Estimates of prevalent aHUS population in the USA

Cohort No. Cumulative No. Cohort No. Cumulative No.
Prevalent ecu. treated  2011 to 2016 (Base)    1110* 1110 445** 445
Prevalent ecu, treated 2016 to 2020 + 1000 2110 +400 845
Ecu. Treatment growth + 200 2310 +80 925
On Trial pre-2011 +100 24 10 +100 1025
Untreated in remission 2011-2020 +250 2660 +100 1125
Historic in remission +450 3150 +180 1305
Untreated dialysis +150 3300 +60 1365
Deaths -205 3095 -80 1285
Prevalence per million 9.4 3.9

*based on the 222 actual patients in database representing 20% of all USA patients.
**based on the 222 actual patients in database being 50% of all USA patients

If the prevalence  of aHUS patients in 2020 is approximately 3095  then the USA aHUS prevalence rate has grown to 9.3 per million of the population. Intuitively,  the surviving aHUS population should be increasing with access to eculizumab. Prevalence rates used  10 years or more ago should now be considered out of date.

aHUS alliance global action based its estimate of current prevalence by starting with an accurate patient prevalent population in one US database. Then it makes assumptions about aHUS patients  in  other hospitals and the possible growth of eculizumab prescriptions with more awareness. It also  assumes  patient numbers for those untreated in remission or awaiting transplant ( with eculizumab) and/or left behind not being able to have a transplant. The  total  Is then reduced for those patients who sadly may have died in the past 8 years or so.

There could be some double counting and over statement. If  the 222 aHUS  patients did not  represent 20 % of all patients  but were 50%, or a different percentage of aHUS treated patients in the USA in that period, prevalence could be over stated.  Maybe the growth of treated patient numbers in 2011-2016 included a ” catch up” element , a temporary  spike in treatment “incidence”. One which could have disappeared in the period  2016 to 2020. On the other hand there  could  be some under-counting and underestimating of the historic untreated aHUS patients.

Either way the traditional prevalence rates appear to  no longer reflect what is happening in the USA today.  Instead of a prevalence between 1 to 2, it is more likely to be  between 4 to  9 per million and growing. Only one aHUS population study has found an aHUS prevalence rate of  9 per million. That research was carried out in 2016 by Dr Gianluigi Ardissino, but limited to children with aHUS within the North of Italy. In a small number of studies in  other countries in Europe, as well as Australia and New Zealand, six or more years ago, the lower prevalence rate was found to be more likely.

Even the results from splitting the difference in prevalence rates would  give  a more positive and encouraging picture for those affected , and yet to be affected , by aHUS in the USA. More and more patients are surviving.

The survival prospects form USA  aHUS patients who have considerable access to eculizumab ( as well as Ravulizumab) and medical facilities should have increased considerably in the past 8 years. Prevalent numbers must have grown. The hundreds of millions spent on treatment should have  made a big difference.

Maybe the incidence rate to has grown too because awareness of aHUS has improved the identification of aHUS patients leading to more accurate diagnosis  ( something that has been observed in France). AT the upper incident  level of around 300 new on-setting patients per year , the incidence of aHUS in USA  would be just over  0.9 per million. At the lower incidence it would be just less than  0.4 per million.

As a result it would be more probable that by 2022 there would be between a further  240 to  600 or more new patients, than the  8 to 16 if the population continues to grow.  An incidence rate of over 0.4 per million is highly likely.
One final  thought about the spectrum of aHUS patients in 2020.

If the characteristics of those 222 aHUS patients in the Premier Perspective Hospitalisation Database are representative,  Table  2 gives some new insights perhaps of  what aHUS patients in USA might look like at  the upper and lower prevalence levels,  including a “split the difference“ ( well almost with a memorable figure at least for this year!) prevalent population for argument’s  sake, but which might be nearest the mark.

Table 2 Characteristics of prevalent USA aHUS population

USA aHUS patients %  patient prevalence
Global Action’s
”Split the difference” patient prevalence  2020
White 63.5 1966 816 1283
Black 20.0 619 257 404
Other 16.5 510 212 333
< 18 years 17.5 541 225 388
> 65 years 16.5 510 212 356
Female 65 2011 835 1313
Late diagnosis 67.5 2089 867 1363

aHUS in the USA is  still  an extremely rare disease with a prevalence well below the USA rare disease definition of a rare disease affecting less than 200,000 of the population.

It is still looks  predominantly white and  female, but with  much more ethnicity and seniority now  and with relatively fewer young people because of a lower prevalence rate in children (5.2 per million) compared with adults (7.2 per million).

aHUS alliance Global Action believes that overall in 2020 , a more up to date prevalence rate of 6.5 per million would place the aHUS patients population in the USA  at over 2000 ….and rising.

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