England recommends Ravulizumab for aHUS

Article No. 435

20 May 2021

There is a  saying that  “you can wait ages for a London bus but then two or three will come along together”

It feels a bit like that as yet another “ravulizumab for aHUS” decision is announced in the UK. ( see article number 434 for the Scottish announcement)

On the day that The National Institute for Health and Care Excellence , NICE, has approved the use of Ravulizumab for treating PNH  in England, it also says that its Committee has issued a draft guidance document  for ravulizumab to be used for aHUS too.  The newer version that is , 100ml/10mg*, which has an  the infusion time nearer to eculizumab levels, as well as the extended  8 week interval between infusions.

As a result of its decision, the guidance NICE gives can be adopted  in Wales and Northern Ireland too , but first  the health authorities there need to decide whether they wish to accept that advice. That can take up to two months from the  final announcement but it does not involve another separate evaluation. The full announcement can be read HERE.

When all that is the done the whole of the National Health Service  in the UK will have shifted  to the new technology.

Meindert Boysen, deputy chief executive and director of the Centre for Health Technology Evaluation at NICE, said: “Living with a rare blood condition can be both physically and mentally challenging, especially when frequent treatment is required.

“We are pleased to be able to recommend ravulizumab for people who have paroxysmal nocturnal haemoglobinuria or atypical haemolytic uraemic syndrome.

“We are hopeful that the increased time between doses with this new treatment will lead to a better quality of life for these individuals and their loved ones.”

Ravulizumab use is much more cost effective than eculizumab. Clinically it is not inferior. Patients get quality of life benefits from the four fold increase in the interval between treatments.

There is still the diagnosis uncertainty that aHUS frequently presents to be dealt with, so it means that eculizumab will still be used for the 20 to 30 new on set patients each year, until it can be established that blocking the patient’s C5 has worked. Then a transition can happen.

That delay may not be the case for those who have a known susceptibility to aHUS because of  familial links or prior genetic testing.

The existing 120 or so  patients on eculizumab are eligible to transition to ravulizumab. This will be coordinated in the shared care way between the aHUS Centre in Newcastle upon Tyne and the patient’s own health carers. No date is set at yet but it could happen later this  Summer.

The decision means that all aHUS patients throughout the UK  will be able to access treatment when needed for free at point of delivery. An excellent position for an aHUS patient to be in when this devastating disease has struck.

Once again the patients helped in the decision making. Volunteers participated and made a robust case for aHUS alliance Global Action to use. Overall they had a positive opinion about the use of ravulizumab.

Now that the evaluation process has ended the full unabridged version used can be read below.  It includes the views of 5 UK patients along with the 13 transitioned patients from the USA.

Additionally NICE  heard the testimony of an aHUS patient from London who has had experience of eculizumab treatment for his aHUS for over five years..

Following the announcement aHUS alliance Global Action has said ” Subject to no one successfully appealing against NICE’s world class decision, and we will definitely be not, both the NICE’s and SMC’s  decisions will be  excellent news for patients in the UK. Ravulizumab will make their lives freer and easier while keeping them safe from aHUS, a harmful, life threatening and very rare disease. We hope that this  will be the case in other countries around the world too”  

*the study was undertaken before the newer 1,100 mg/11 mL and 300 mg/30 mL concentrate for solution. The newer advanced formula will be used in the UK from the outset.




Version: 4/10/2020

aHUS alliance Global Action


Atypical Haemolytic Uremic Syndrome, or aHUS, is an exceedingly rare life-threatening thrombotic microangiopathy, or TMA, which damages the kidneys in particular because of uncontrolled activation of a genetically defective, or otherwise hampered, part of the innate immune system called Complement.

 Since 2011, when it was first licensed to be used, the most clinically effective treatment of aHUS has been a human monoclonal antibody called eculizumab. It inhibits unregulated Complement activation and stops TMA activity. It is delivered to patients by infusion of weight related doses, usually at two-weekly intervals.  Infusion access is made via an implanted port, or direct into a vein or into a fistula for those patients who have been on haemodialysis (sometimes needled by patients themselves).

Another Complement inhibitor called ravulizumab has been developed by the same manufacturer. This too is a human monoclonal antibody identical to eculizumab but re-engineered with changes to four points in the amino acids chains of its chemical construction. The modifications result in a prolonged active half-life of the effective ingredient and therefore extends the interval between infusions. Maintenance dose infusions are usually administered at eight-week intervals for adults and a four-week interval for small children.

The non-active ingredients included in the final product are the same for both eculizumab and ravulizumab. Ravulizumab is, however, mixed into a bigger bag of saline for infusion than that used for eculizumab because of the higher number of vials of ravulizumab used per infusion. An infusion of ravulizumab can take more than three to five times longer than for eculizumab, which generally took thirty minutes to one hour.

This report describes the impacts experienced by aHUS patients who have transitioned from eculizumab to ravulizumab treatment as well as the impact expectations of aHUS patients who are yet to transition from eculizumab.

The specific focus of the study is the delivery of both treatments rather than their clinical benefits compared with no treatment or a historical perspective on how disease management has changed over time. Participants weren’t asked about other treatments which they may be receiving.

  1. 2.Methods Used

The research was conducted between 3 August 2020 and 12 September 2020. There was no conflict of interest amongst any of the participants contributing to the study.

The method used was chosen because it was impractical to conduct extended and recorded face to face interviews in the time available. Interviewees felt comfortable with writing and talking about their experience.

The study report is therefore based on the results from 13 online interviews with people with direct experience of both treatments and 5 online interviews with patients with experience of eculizumab only. No volunteers with experience of ravulizumab only participated in the study.

Participants volunteered to give statements following a social media call on 3rd August 2020 via the aHUS alliance Global Action’s website, Facebook Page and in a closed aHUS Families Facebook Group, for patients with experience of both eculizumab and ravulizumab use. Although though the call for volunteers was to global aHUS patients, only patients from the USA offered to participate. The characteristics and time on both treatments of the participants are given in Table 1. The group’s average time on eculizumab had been 4 years 5 months and 7 months on ravulizumab.


Table 1: Characteristics and treatment duration of experienced participants



Participant’s Role Gender of patient Age at August 2020 Time on eculizumab


Start month Time on ravulizumab


A Patient Female NK NK NK NK
B* Patient Female NK 4y 11m 5/20 4m
C Patient Female 46 9m 4/20 5m
D Patient Female 68 2y 1/20 8m
E Patient Female 51 6y 6m 12/19 9m
F Carer Male 11 10y 5m 2/20 7m
G* Carer Female 13 6y 11/19 10m
H Patient Female 47 6y 1/20 8m
I Carer Male 13 5y 6m 12/19 9m
J Patient Female 62 3y 1/20 8m
K Patient Female 38 3y 4/20 5m
L* Patient/Carer Male 23 1y 2m 5/20 4m
M Patient Male 22 4y 6m 12/19 9m

*transplant patient     y -years    m-months

The US Food and Drugs Agency (FDA) approved the use of ravulizumab on 18th October 2019 and so, by the time of this study, all experience of ravulizumab following transition is limited to less than a year, and to between 2 to 5 treatment cycles. No respondents had participated in any ravulizumab trial.

Participants provided some initial information when offering to volunteer, but all were written to with a further explanation of  the purpose of the research, and what was expected of them,  and to give assurance that information would be kept in confidence and  participants anonymity would be maintained. Each was asked to write freely about what mattered to them in the transition, but some topic areas were suggested for them to think about. A follow up individual meeting by Zoom was offered and taken up by seven of the participants to clarify statements made and add further experience comments.

 Each was asked about their length of time on both therapies.  Details about their aHUS onset experience and recovery were not asked for but three volunteers mentioned that the patient had a kidney transplant.

For volunteers with experience of eculizumab only, known UK aHUS patients on eculizumab were contacted by telephone/messaging, and told about the research being done and asked to volunteer to participate. None of them had experience of using ravulizumab and each had little knowledge of the new technology other than the time for infusion was longer than for eculizumab, but so too was the interval between infusions. The characteristics of the UK eculizumab only participants are given in Table 2. The group’s average time on eculizumab has been 6 years 2 months,


Table 2. Characteristics and treatment duration of UK participants

Participant’s Identifier Participant’s Role Gender of Patient Age at August 2020 Time on Eculizumab
A Patient Female 28 5y 6m
B* Patient Female 46   5y 10m
C* Patient Female 51 5y 2m
D Patient Female 34 10y 4m
E Patient Male 37 4y 3m

* transplant    y-years m-months

In an email exchange volunteers were asked to write freely about what mattered to them in a potential transition from eculizumab, but some topic areas were suggested for them to think about. Each was asked about their length of time on eculizumab.  Details about their aHUS onset experience and recovery were not asked for but two participants mentioned that they had a kidney transplant.

 The responses from both the “experienced” and “expectant” participants were pasted to a summary document for analysis. Themes were identified and comparable and contrasting views of participants summarised. This work was done by the Trustees of aHUS alliance Global Action.

The results from the experienced group are given in Section A and the expectant group in Section B. In both sections direct quotes from interviewees appear in italic and are attributed to the role of the interviewee; patient or carer, as stated in the relevant Tables 1 and 2.

  1. Results

 Section A – Impact statements from patients who have transitioned from eculizumab to ravulizumab treatment.

A1. Transition process

The earliest transition from eculizumab to ravulizumab occurred within a month of FDA’s approval of ravulizumab on 18 October 2019. Seven respondents said they had transitioned by the following January.

From those who disclosed it, the impetus to change mostly came from the patients themselves. They reported that they had been watching and waiting for FDA approval and had sought the move to ravulizumab when it became possible. For others it was their clinician who recommended a move. Several stated that their insurance providers were eager for them to change to ravulizumab treatment. Overall patients were keen to try it and generally were relaxed about doing so.

My doctor pushed for my switch to ravulizumab, but also my insurance company did as well, I’m assuming because it is less expensive(Patient C)

With the FDA approval of Ravulizumab in October 2019, I requested the changeover immediately, but it was not cleared until January 2020 (Patient D)

Once the FDA approved ravulizumab, I contacted my doctor as well as the employer providing my insurance, because they started directly paying for my eculizumab treatment when their re-insurance denied coverage after a year. My doctor approved the change (Patient E)

My son’s doctor did first mention the medicine to us and started the process of insurance approval once it was FDA approved. It took about 3 months once the new medicine was FDA approved for both the hospital board to approve getting the medicine and insurance to preapprove the new medicine (Carer Patient F)

The transition was our choice.  As soon as we heard of the FDA approval, I contacted our son’s physician to begin the process.  Our son was the first non-clinical trial paediatric patient in the US to transition (Carer Patient I)

I learned about the new drug being approved from a nurse in the infusion room…. so, I told the doctors I wanted to move to the new drug… insurance approved, and we moved (Patient J)

My doctors told me about ravulizumab so deciding to do it was nothing too crazy, whatever if it’s better.  (Patient L)

Once approved, the date for the transition protocol to be enacted was set. Two respondents reported some problems with meeting due dates but most reported that the move went to plan with no logistical issues. One mentioned the role played by their “case manager” in helping coordination.

My case manager was vital in coordination of many aspects between doctors, suppliers, facilities, and new nursing company (Patient E)

I started in April of 2020 I believe…then got off a week or so because of a pharmacy mistake (Patient K)

A2. Infusion Process

Two weeks after the last eculizumab infusion a loading dose of ravulizumab is administered. After a further two weeks the first maintenance dose begins and is followed up 8 weeks later and then so on. All respondents reported being on 8-week intervals between doses. No respondent commented on the volume of ravulizumab they were prescribed. On prompting at interview, two respondents reported that 10 and 11 vials of ravulizumab were prescribed according to their weight. (Note: compared with 16 vials of eculizumab for four treatment cycles over an eight-week period).

The increased length of the time taken over each infusion was mentioned because it was considerably more than for eculizumab, typically 2 to 5 hours, compared with 30 to 60 minutes reported for each eculizumab infusion. So, it is only marginally more than the aggregate time for four separate eculizumab infusions in eight weeks. Patients saw an advantageous quality of life trade-off between having longer infusions and gaining a greater interval between infusions.

Participants reported that not having to attend for infusions every two weeks was a major benefit. Apart from the time gained to do other things, they mentioned how fewer infusions brought a physical and mental relief to the burden of treatment and made life easier for them.

One eculizumab home infusion patient reported a reversion to infusion centre practice for the first dose of ravulizumab so that any reaction could be monitored.

One carer mentioned that her son’s access port has been removed to avoid unnecessary hospital visits for line flushing between infusions. Another carer of a patient with a transplant reported her daughter’s port was retained for transplant monitoring procedures.

Another respondent reported that the loading dose of ravulizumab followed soon after an Ileostomy operation. The patient felt poorly at the time, with headaches and fatigue, but whether these were attributable to surgical recovery or ravulizumab was unclear.

Benefit from longer time in between infusion, thus giving my veins a rest. (Patient C)

My first treatment was delivered at my prior infusion facility to watch for reactions then returned to home infusion.  (Patient E)

My son has been on eculizumab for all but 4 months of his life and is used to having infusions. Initially he was apprehensive about the extended infusion time but quickly adjusted when he realised it gave him more permitted time on his iPadHe had his port removed to avoid the need for flushing between 8-week infusions.  (Carer Patient F)

I had a surgery to make my ileostomy permanent mid-December then transitioned to ravulizumab the first week of January. The recovery from surgery was more difficult than expected, but the team felt I should still transition in January. I felt poorly but I think that was from surgery more than the new med.  I’d say the headaches and fatigue were worse. (Patient H)

The frequency of every 8 weeks has changed patients mental thinking.  Going every 8 weeks, it is not so “in your face”.  (Carer Patient I)

While the infusion is longer, anywhere from 2-5 hours, having 8 weeks to live my life without thinking about the logistics of my next infusion is so freeing. (Patient M)

A3. Efficacy of the Technologies

Most respondents were confident that ravulizumab would be as effective for treating their aHUS as eculizumab had been.

My husband and I saw detailed data on the upcoming ravulizumab and were convinced it was as effective as eculizumab, particularly at keeping complement C5 shut down for the full 8 weeks in over 99% of cases (Patient E)

 Several respondents mentioned that their blood results showed little difference following transition, with one respondent reporting a slight improvement after ravulizumab treatment. One patient, who transitioned, immediately following an operation, reported that the clinician had undertaken weekly blood tests in between infusions. Another respondent mentioned that the CH50 blood test was not available for ravulizumab treatment which raised her concern about monitoring efficacy.

The doctor says his labs look great so far and indications are good that the drug is doing well. (Carer Patient F)

My bloodwork has been monitored more closely than before… my clinician decided to take weekly bloods after the early infusions but phased them out over time…ravulizumab is proving to be just as stable as with eculizumab. (Patient H)

…there seems to be a lack of available blood testing to analyse complement blockade in ravulizumab, compared to CH50 with eculizumab. (Patient I)

Since January, all my lab numbers remain intact. (Patient J)

Eculizumab cured all aHUS related health issues and ravulizumab does the same….my blood tests normalized after my initial diagnosis and have remained normal while I’ve been on eculizumab and ravulizumab. (Patient M)

A4. Side Effects

One respondent reported a side effect from ravulizumab so serious that a reversion to eculizumab was needed. Full details of the reason for the reaction were not provided. As this was the only comment made by the respondent it is not known whether this was reaction to the re-engineered eculizumab, the change in infusion practice, or some breach of transition protocol affecting trough dose.

I went from long term eculizumab to ravulizumab …had side effects on ravulizumab and I’m now back on eculizumab (Patient A)

Respondents’ comments about other side effects were mixed. Some reported that they had no side effects with both eculizumab and ravulizumab; or the side effects were similar from each drug but limited to the infusion day or the day after. The most frequently cited side effects being a regular transitory headache and fatigue in the days following each infusion. Others mentioned included mild joint pain, sore throat, numbness in nasal/sinus area, pain at end of fingers/toes. Where asked, no patient regarded the side effects as debilitating. A small number of respondents felt their side effects were less after an infusion following ravulizumab transition. One respondent considered that the same side effects after treatment were stronger. Another who experienced a reaction to ravulizumab infusion found slowing down the rate of infusion improved matters. Although not leading to a reversion to eculizumab yet, one respondent felt that the bloating and an inability to lose weight while on ravulizumab is making her think about going back to eculizumab treatment.

The side effects I experience seem to be a little stronger than with the eculizumab. They are, tiredness, (3-4 days after infusion) more intense joint pain, sore throat, and headache.  (Patient C)

I had no reactions or side effects at any point on ravulizumab (or on eculizumab) (Patient E)

My son has had no obvious side effects with either medicine (Carer Patient F)

After my daughters first infusion she had an overall feeling of not feeling well, mostly body aches, so we decided to pre-treat with painkiller. That had helped and she really has had no other side effects (Carer Patient G)

I have not experienced any side effects that I didn’t have with eculizumab. I think I have fewer headaches and less fatigue now than I did with the eculizumab. (Patient H)

I still have had no side effects from ravulizumab (Patient J)

with my inability to lose weight and the bloating the ravulizumab is causing, I really don’t know if I want to stay on it.  (Patient K)

I feel tired and “not so good” on the day of the infusion and the next day and then I am ok again. (Patient L)

I have had a minor complication, and I never had issues with eculizumab. With ravulizumab the manufacturer recommends providers infuse over 2 hours. Unfortunately, for some reason, my body couldn’t handle the drug at that rate, and I had a bit of a reaction the first time I used it. I’ve since slowed the infusion to 4 hours which I’ve been able to handle with no complications.  (Patient M)

 No respondent mentioned any concern about the major side effect from both drugs, i.e. the risk of a meningococcal infections. This perhaps indicates that they thought that any mitigating action taken for eculizumab would apply to ravulizumab too.

A5. Work, School, and Other Activities

Apart from a physical and mental relief from going through the infusion process less frequently, all respondents remaining on ravulizumab refer to the longer intervals as a key benefit, a “game changer”. Respondents appreciated and made use of the new “freedom” it gave. The benefits are also felt by carers of patients.

…gives me more freedom because I don’t have to worry about scheduling infusions as often… I would say that my day to day life has improved because of the longer time in between infusions. I am able to plan more activities, trips, etc.   (Patient C)

 Ravulizumab has certainly helped improve my lifestyle with having six versus twenty six infusions over a year period… my family live in Thailand and a two weekly infusion cycle, unless special carriage of properly stored eculizumab vials is arranged for away from home infusion, limits time I can spend there on visits. Ravulizumab improves my freedom to travel and stay longer.  (Patient D)

The telling life story was that for the first time in 6 years, I didn’t have to schedule an infusion during the holidays! Or arrange my vacation around it.  (Patient E)

The time between infusions is a game changer as far as missed school for my son and missed work for myself.  (Carer Patient F)

… as a nurse missing work as often as I did with eculizumab treatment caused me stress, that it might affect my salary status…ravulizumab has saved me a lot of lost work time, and less use of my precious PTO (paid time off) time … (Patient H)

Missing school once every other week was challenging (especially at higher grade level with multiple teachers). Infusion Center is 2 hours (100 miles) from home- 4 hours travel time, plus fuel and meals… we would also be able to spend more time at our holiday home on vacation as we will not need to return for infusion  (Carer Patient I)

with not having to plan my entire life around every other Wednesday for medicine is a huge advantage.  (Patient J)

I wanted to switch for the convenience really. I work full time, plus my husband and I have 3 boys to raise (Patient K)

I would say he has more time for his favourite pastimes, walking and fishing as well as for his full-time job…. we even went on vacation last month to Arizona, 12 hours from here, that is something he would not have done on eculizumab, to go so far away from his home base and treatment (Carer Patient L)

Eculizumab ruled my life. I couldn’t study abroad like the typical undergrad, since I needed to coordinate insurance, doctor’s care, and eculizumab infusions every two weeks. My insurance company said they would cover two “grace” infusions abroad a year, but that would only allow me to spend a maximum of 6 weeks out of the country. The typical college study abroad program is 5-6 months. (Patient M)


A6. General health

No respondent mentioned the state of their, or their child’s, general health but, when asked, they described it as “excellent” and transitioning to ravulizumab made no noticeable difference to that status.

… I feel so much better I have begun training to do a triathlon. (Patient H)

It is like my illness was a dream, unreal, because I feel so well on both drugs, like I was before it happened(Patient J)

A7. Expense

A small number of respondents commented on the reduced cost of treatment they had observed, not just because of a lower  price and fewer vials of ravulizumab needed at their weight, but from the savings also accrued due to less frequent infusion centre use and travel for treatment.

 and the health coverage provider told me it would save them 30% in overall costs.  (Patient E)

 Based on the figures I see from my insurance company; one other benefit is that it appears that ravulizumab infusions will cost much less on year than eculizumab did.  (Patient J)

A8. Other Issues

One respondent reported that she had experienced a COVID 19 infection earlier in August 2020. The course of the disease, although typically symptomatic, ended quickly and she was in quarantine working from home. There had been no problems from being on ravulizumab.

Other than that one respondent, the rest of participants mentioned no other issues other than topics summarised above.

In particular no one mentioned any change in their opinion about withdrawal from treatment. There was also no mention about treatment whilst pregnant.

A9. Overall Opinion

Most of the respondents reported that they were, on balance, satisfied with the transition from eculizumab to ravulizumab and preferring to be on ravulizumab. Ravulizumab makes life easier. Some considered that both were necessary.

I definitely prefer ravulizumab…. ravulizumab I feel is a step above eculizumab (Patient C)

You have to have both eculizumab and ravulizumab available as options. It seems like some patients do better on one or the other. Some have had to go back to eculizumab.  (Patient E)

Overall, she has done really well with the switch and she has not regretted it. (Carer Patient G)

My experience with ravulizumab has been phenomenal…I’m extremely happy with ravulizumab, and very grateful I get to have it (Patient H)

I can breathe, I feel better not having so much treatment, it’s simpler to do, making life easier. (Patient L)

Switching to the 8-week ravulizumab has been an incredible blessing (Patient M)

SECTION B – Expected impact statements from patients who have experience of eculizumab only

B1. Transition process

Unlike patients from the USA, the UK patients were not anticipating the approval of a license by the European Medicines Agency. They did not seek it from their healthcare provider as soon as it was announced, being aware in any case that it would require further approval for all to benefit sometime in the future. They expected that once approval was given that careful coordination of the switch between eculizumab and ravulizumab would be needed to avoid mishaps.

I would hope that Newcastle will liaise with my consultant, who would liaise with homecare and the pharmacists, there does seem like a lot of potential for things to go wrong there! It would be helpful to get an information pack with details of the plans and reassurance of how the new drug works, perhaps an online question and answer session too (Patient B)

 I realise there will be some transition stage from eculizumab to ravulizumab. I assume that Newcastle will contact my hospital who will then contact the homecare provider. I know that ravulizumab has a loading dose but after that I have no idea what the procedure is. (Patient C)

I would expect everyone involved, including the patient, to have a good working knowledge of ravulizumab and that the transition will be explained fully. From my memory of starting eculizumab the transition from plasma exchange was smooth – I would expect this to be the same (Patient D)

B2. Infusion Process

Participants were aware of the longer infusion time and the increase in the interval between infusions. UK patients placed more emphasis on fewer infusions bringing greater relief from the pressure, anxiety, and the damage from each infusion. Those receiving the infusion via a port catheter had concerns about what would be changed because of the longer gap.

…I also hate needles! Almost 7 years of infusions and it still isn’t much better! The anxiety of a new nurse every 2 weeks who doesn’t know you and can’t access your veins isn’t great so having to face this fear only every couple of months would be truly amazing! The more time goes on, the more visibly scarred my veins are becoming so being able to reduce that too (Patient A)

Different nurses every two weeks is another intrusion and their skills and knowledge vary greatly. The dread of having a nurse who you know struggles to cannulate you is awful and being calm whilst they stick you with a needle several times is very hardWeek to week freedom, my infusion time is not guaranteed, so I can’t make plans for Tuesdays every other week and when I was struggling with access two days either side. I have had to cancel plans made weeks in advance for one opportunity events but was made to feel that I had to fit into their very inflexible service. That did not feel good. It is hard to commit to others when planning something in the future which impacts on friendships. It is very difficult to change the infusion time and if you have to you risk issues with delivery etc.  (Patient B)

Reduced anxiety of treatment once every 8 weeks and not every fortnight…but will ports require heparin lock with the length of gap?  (Patient C)

I find myself stressing about when the next infusion is, with that comes deliveries and timings that can be stressful too. I think I will feel a huge weight is lifted with 8 weeks breathing space….at present I cannot guarantee which day my infusion will be on every 2 weeks. I think I will just feel so much more ‘normal’ and enjoy the freedom to live life to the full.   (Patient D)

B3. Efficacy of the Technologies

The UK patients’ hope that ravulizumab would be as effective a treatment as eculizumab, which was the view of the US patients.

 I just assumed and trusted that it would work as well and didn’t consider the risks of coming off eculizumab the drug which keeps my much longed-for kidney transplant safe. I suppose I must trust the science and, as with eculizumab, I just believe it will work as well and keep me safe (Patient B)

I would like to think I would continue to be stable on ravulizumab as I am on eculizumab.  (Patient D)

B4. Side Effects

Unlike US patients, the UK patients were more dismissive of the side effects of eculizumab/ravulizumab infusions though experiencing some transitory effects following each infusion. Particularly those who had long term experience of other more burdensome and damaging treatments. One patient considered whether ravulizumab impacted on the major side effect of complement inhibition i.e. meningococcal infection but expected current protection from the risk to work.

I know whatever the side effects are they will be better than side effects of dialysis!! People tell me there are side effects of eculizumab, but I don’t experience any. I have my infusions and go! I have had heard the side effects maybe worse but perhaps, as I don’t get any, I still won’t. I think you can become hypervigilant to symptoms when you have a new drug, but I’ll try to just truck on!  (Patient B)

Risk of meningitis altered…. already on antibiotics so no other changes in meds needed.  (Patient C)

I appreciate that newer patients struggle with side effects, but when you have survived purely on plasma exchange for 5 years as I did you don’t complain about side effects because you know what life is like without these miracle drugs!   (Patient D)

B5. Work, School and Other Activities

The UK patients expected, as the US patients have experienced, that the longer interval between infusions would have a significant impact on their working life, business opportunities and leisure. Some saw the opportunities for travel that they had put to one side while on eculizumab. Others who had travelled considered that the pressures of the uncertainties of being away from home would be lessened and would make such journeys more relaxing and “normal”.

Working arrangements can be difficult when you work shift patterns in a hospital and need to constantly change your shift at short notice to accommodate your infusion, but not only that having to arrange the delivery and make sure someone is around to sign for it although you work all week can be awfully difficult; holidays are tricky to arrange as you have to assess your whole calendar and move your treatment dates sometimes which can take weeks due to the 48hr window   (Patient A)

I have travelled and had my infusion away from home but that is very stressful and does impact on the holiday, the day before with the worry and the day of the infusion. Having an infusion on holiday means you miss out and is another reminder that you are not ‘normal’ like everyone else. Going away without having the infusion is also difficult because you are worrying about delays or problems getting home for your infusion. The Icelandic eruption would have been a disaster for my transplant and the recent pandemic too!  (Patient B)

…can finally go on long-haul holidays and not limit to 12 nights in case of cancelled flights (Patient C)

I was diagnosed at 19 and it has always been my dream since that I would be able to travel. Eculizumab allowed me to travel for 2 weeks, but I always felt nervous that something might happen to prevent me returning on time for my infusion. With an 8-week regime I could satisfy my travel bug and feel confident I would have time if any travel plans are affected.  (Patient D)

I run my own consultancy business, working for global organisations fixing commercial issues on a short- term project basis. Quite often, last minute projects or requests have come in that required me to travel with little notice. With the two-week schedule of eculizumab, I have been unable to take these jobs and lost out on lucrative jobs  (Patient E)

B6. General Health

UK patients did not expect any health improvement resulting from a switch to ravulizumab, other than a rumoured reduction in hypertension. The main health benefit foreseen would be in their mental health with the reduction in stress and anxiety about treatment.

The same as eculizumab it will improve my quality of life and my longevity. I would like to think the less regular infusion will reduce the stress and anxiety over infusions and allow me to feel more confident and capable. I will continue to be active without the interruption of infusions!  (Patient B)

I can guarantee you that my mental health and relationships will improve at least 10- fold. (Patient C)

I imagine one of the biggest impacts of Ravulizumab will be on my mental health. I can’t emphasise enough the feeling of freedom this will give. I am a determined person anyway, but having this much time in between infusions will mean I can go for gold without any excuses of infusion dates etc. I don’t always realise the impact of what having a long term, life changing illness can have on my mental health. It is only when I stop and look at it that I can see how trapped within aHUS that I can still feel even though I presently have 2 weeks between infusions (Patient D)

I would very much like to put more time between treatments as I feel this would improve my mental health (Patient E)

B7. Other Issues

Two respondents acknowledged the potential benefits to family/carers living with someone on ravulizumab treatment. Firstly, there would be less stress on and worry by carers about their support for home infusions etc, and greater career opportunities for spouses.

My family won’t have to remember to stay in for the delivery of the drug every two weeks and the stress of whether it will arrive every two weeks. It won’t have to be factored into planning our lives. Less stress with less frequent infusions and nurses who are strangers coming into the home. Feeling ‘normal’ like everyone most of the time. Less worry on holidays… Less worry for family wondering if infusions went ok.  (Patient B)

My wife has twice been offered significant career opportunities that would require us living in the USA for a large part of the year. She felt compelled to turn them down due to my treatment schedule and proximity to care team. We’ve agreed that we wouldn’t feel comfortable moving my healthcare away from the team at my hospital as we had bad experiences leading up to diagnosis getting the care I needed. However, if I was on ravulizumab it is feasible that I could manage my treatments, clinic appointment & travels to allow my wife to take these opportunities without feeling we’re risking my health & care.   (Patient E) 


B8. Overall Opinion

UK patients felt the same as those from the USA about being able to access ravulizumab as a new treatment, that it would be preferred and add to the quality of their lives.

Being able to transfer my treatment to Ravulizumab would mean that my quality of life would be greatly improved…it may not sound like a big deal, but when you’re lived through your 20s with that bind when seemingly everyone around you has not a worry, it can be upsetting. To be able to get the last couple years of my 20s with such an ‘easy’ treatment option… amazing!!  (Patient A)

Excited and probably when it comes to it nervous!   (Patient B)

When we were allowed eculizumab I thought that was a life changer. But to have it every 8 weeks would be a miracle. I honestly can’t wait for this change. (Patient C)

For the last 15 years I have required medical intervention at least every 2 weeks to keep me alive – the idea of having 8 weeks between medical treatments is amazing! When I was first diagnosed in 2005 the outlook was bleak, I can’t quite believe there could be an opportunity to have a life that resembles ‘normal’. I am stable on eculizumab and have been for over 10 years, whilst the idea of ravulizumab is very exciting I must admit there is a feeling of apprehension that it could be too good to be true.   (Patient D)

My expectations for moving to ravulizumab are great and varied, as I am truly excited by the freedom the change in treatment schedule would make to my life.  (Patient E)

  1. Conclusion

From those USA patients with experience of both technologies, as well as the expectations of those in the UK on eculizumab now, the most telling benefit of ravulizumab over eculizumab is the substantial reduction in infusions needed, which increases the time between infusions considerably.

The fewer treatments reduces the cumulative pressure, anxieties, and practicalities of each treatment over time, as well as releasing additional personal time to do other things, including those put off because of the insufficient inter-treatment gap e.g. long-distance travel for leisure or education.

Of lesser importance to US participants, and even less so to UK patients, were the side effects of the new treatment. Most found little difference in post infusion transitory side effects, whether they had experienced any or none on eculizumab. Some perceived an improvement and two felt side effects had been sufficiently worse to revert, or think about reverting, to eculizumab. Those who had experienced and were aware of the long-term side effects of plasma exchange and dialysis therapies did not regard the transitory side effects of an infusion as burdensome.

With one exception, following transition participants had not observed any deterioration in the general health they attained whilst on eculizumab treatment. This was usually claimed to be excellent. UK patients saw mental health improvements as more likely.

With only minor logistical hiccoughs reported, the transition from one drug to another in the USA was not perceived as difficult to do, and so was not a matter of importance. Similarly, UK patients saw the potential for things going wrong, but which could be manageable by all parties involved in delivery.

Taken all together, patients with experience, and those with expectations, regard ravulizumab as adding to their quality of life. Although it was not within the scope of this research to measure and quantify a value of the quality of life added, based on what has been voiced by participants it can be confidently predicted that it would be more than zero.

From the evidence provided by those with experience of both eculizumab and ravulizumab treatments, as well as those with eculizumab experience only, patients see ravulizumab as a positive and progressive step change to their treatment. Although not perfect yet, it has much to commend it and is welcomed by aHUS patients.

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