Summary of the National Collaborative Study for Lysosomal Storage Disorders (NCS-LSD) for Gaucher Disease
Final Results Report
August 2012
For: Adults and children with Gaucher disease and their families
WHY WE DID THE STUDY
Enzyme replacement therapies (ERTs) are now available, and licensed in the UK for the treatment of six lysosomal storage disorders (LSDs), including Gaucher disease. In 2005, the Peninsula Medical School, in collaboration with the respective treatment centres, and the Lysosomal Storage Disorder patient support groups, proposed to examine the effectiveness and associated costs of these therapies.
In order to understand how effective ERT is, we collected data from adults and children attending each of the national LSD treatment centres who agreed to participate. By collecting clinical and Quality of Life information from people with these conditions over three years, the National Collaborative Study for Lysosomal Storage Disorders (NCS-LSD) aimed to gain a better understanding of how effective these treatments are and what the associated costs are.
The researchers have now completed their report to the Health Technology Assessment programme (HTA) who funded the study. Once finalised, the full report will be available on the HTA website (www.hta.ac.uk).
HOW THE STUDY WAS DONE
Who took part
At the start of the study, a total of 272 Gaucher patients attended one of seven treatment centres in England. Each patient was considered by their consultant for their suitability to participate in the study (i.e. that they wouldn’t become distressed by taking part in the study) and of the 223 eligible patients, 185 patients were approached in clinic and invited to participate. One hundred and seventy five patients (95% of those approached), including 75 males and 100 females, agreed to take part in the study. Twenty five of the participants were children and 150 adults.
Treatment
At recruitment to the study, 155 patients were on ERT with the average time on ERT being 10.2 years (range 0 to 17.8). Of those on ERT, 142 patients were receiving Cerezyme®, one received Ceredase®, one received taliglucerase alpha and ten received VPRIV®. The type of ERT for one patient at recruitment remained unknown as they were participating in a clinical trial. A further nine patients were taking Substrate Reduction Therapy (SRT; Zavesca®). Eleven patients were not on either ERT or SRT.
WHAT INFORMATION WE COLLECTED
We collected clinical data from every patient who consented to participate in the study, each time they attended their treatment centre between 2009 and 2011. We also collected historical clinical data from participants’ hospital records. In addition we asked participants and their carers to complete a series of quality of life and service-use questionnaires each time they attended their clinic. These questionnaires asked about patients’ general well being, how frequently they use the NHS, the costs to them and their family of having a lysosomal storage disorder, and about the burden placed on the patients’ carers.
WHY WE COLLECTED THIS INFORMATION
We aimed to use this information to compare the quality of life and treatment costs for people who are receiving treatment, with those people who are not. Current and historical clinical data were collected to help us understand whether and how their disease has progressed. In addition, over 50% of the participating Gaucher patients completed at least two sets of quality of life and service-use questionnaires. This has helped us to understand how Gaucher patients’ general well-being is affected by being on treatment, as well as calculating the financial burden for a family affected by this disease.
WHAT WE DID WITH THIS INFORMATION
After talking with clinicians and support groups, we decided to focus on how ERT affected the following outcomes in Gaucher patients:
· Haemoglobin levels
· Platelet counts
· Spleen and liver size
· Bone pain
· Liver function tests (AST levels)
· Quality of life
· Service use
We did not look at the effect of taking SRT on Gaucher disease as there are only a few patients who are on this treatment. Nor did we separately analyse data from different enzyme replacement therapies, but looked at the data for everyone taking any type of ERT.
We then looked at each of these outcomes and developed models to understand how the length of time people have been on ERT affects each outcome and whether taking ERT delays the onset of some of the effects of Gaucher disease, or alters the progression of the disease. We developed separate models for adults and children.
RESULTS OF THE STUDY FOR GAUCHER PATIENTS
Clinical Data
The clinical data we collected from patients with Gaucher disease provides evidence that time on ERT improves each of the clinical outcomes below. Our data suggest that patients experience very substantial improvements in these clinical outcomes over the first 5-10 years of treatment, followed by a levelling off of the treatment effect.
Haemoglobin Levels
Our results show that time on ERT significantly improves haemoglobin levels in children and in adults.
Platelet Counts
Because platelet counts are affected by having a splenectomy, we looked at adults who have had a splenectomy separately to those with an intact spleen. Our results show that time on ERT significantly improves platelet count in children, and in adults, irrespective of whether or not they have undergone splenectomy.
Spleen and liver volumes
Our results show that spleen and liver volumes are significantly reduced in patients on ERT compared with patients who are not on ERT.
Liver function
Our results indicate a strong association between time on ERT and improved liver function (AST levels) in adults. Patients on ERT have a lower risk of having an “abnormal” liver function than patients not on ERT. No link between ERT and liver function was found in children, but this was possibly due to a lack of data.
Bone pain
Our data suggest that ERT may be associated with a reduced risk of bone pain in adults and children.
Patient-reported Quality of Life data
In order to understand what effect ERT might have on quality of life, we used three sorts of questionnaire – the SF-36, the EQ-5D and an age-appropriate version of a children’s questionnaire called the PedsQL.
When looking at the answers provided by patients and their carers in the questionnaires, we found no evidence of a link between time spent on ERT and patient-reported physical or mental quality of life, as measured by the SF-36 and the EQ-5D in adults, and the PedsQL score in children. Similarly, no association was observed between time on ERT and fatigue, as measured by the Fatigue Severity Scale.
Finally, the results of the Carer Strain Index questionnaire provided no evidence that time on ERT affected the level of care and support given by carers of patients with Gaucher disease.
It is important to note that one of the limitations of this study is that we were not able to collect historical QoL data as this is not routinely collected by clinics. Because most Gaucher patients are on treatment we do not have very much data from patients who are not on treatment. This has limited our analyses to patients who are on ERT, and in many cases, have been on ERT for many years. As a result, we do not have enough data to measure any change in quality of life when patients first go on ERT, or the difference in quality of life of patients on treatment, compared with those not on treatment.
Costs associated with Gaucher disease
Much of the past discussion regarding the costs associated with having a lysosomal storage disorder has concentrated on the costs associated with ERT. In this study we were also keen to capture the wider costs within the public sector, as well as for patients and their families.
Public sector costs
Based on patients’ self-reported health and social care service use, the public sector annual cost of caring for people with Gaucher disease, excluding the purchase cost of ERT or SRT, was estimated at £3,000 for adults and £2,900 for children. Of this, the use of NHS hospital services accounted for about four fifths of costs for adults (£2,400), and three quarters of the costs (£2,100) for children.
Inpatient hospital care accounted for over a third of all hospital costs for adults (£830 per patient per year) and two thirds of all hospital costs (£1,400 per patient per year) for children, while outpatient visits account for about a half (£1,200) of all hospital costs for adults, and about one fifth (£440) of all hospital costs for children. Annual costs for services outside hospital were estimated at £750 per adult and £800 per child with Gaucher disease. Of this, £90 per adult and £120 per child is due to GP visits, while over £500 per adult and £400 per child is due to regular visits from either district nurses, health visitors or other nurses.
The mean annual cost of ERT for adults with Gaucher disease is either £126,300 or £144,900, depending on which ERT drug is used. For children, the mean annual cost of ERT is £107,400 or £187,800.
Costs to patients and their families
The wider financial burden of Gaucher disease on patients and their families, such as travel and accommodation for hospital visits, or carer time at home, was captured using a patient or parent-completed, service use and costs questionnaire.
On average, travel and accommodation costs for attending health services were £67 for each hospital appointment for adults, and £14 for the parents of children with Gaucher disease. This mainly comprises the cost of petrol (for round trips to hospital of between 2 and 800 miles), overnight accommodation for some families/spouses (from £45 to £800) and parking costs (from £3 to £150 per hospital admission). For those travelling mainly by train, the total travel costs per hospital admission were between £2 and £270. The average cost to families or patients per day visit to hospital, per A&E attendance and per GP visit were £44, £13 and £7 for adults and £25, £3 and £4 for children, again mostly due to travel and parking costs.
In terms of help received from family members and friends due to health problems, some adults with Gaucher disease received help for personal care (anything between 1 hour per week and 24 hours 7 days a week, usually from their spouse or partner), help in and around the house, and help with transport/mobility. Some children with Gaucher disease also received family help or care related to their health problems, mostly from parents and siblings, for child care (anything between 2 and 120 hours per week), personal care and transport/mobility.
Finally, in response to open questions, adults with Gaucher disease indicated a very wide range of other costs and impacts of living with the disorder, such as “prescriptions”; “renewed clothing due to weight loss”; “physiotherapy and hydrotherapy”; and “stopped work due to illness”.
Similarly, parents of children with Gauchers reported diverse impacts on family life, such as “home help and home teaching” and “In almost every aspect of life, socially, mentally, [my son/daughter] struggles with learning, concentration, mobility, emotionally and independence”.
OUR CONCLUSIONS
This study provides evidence that ERT is an effective treatment for people with Gaucher disease, and improves the clinical outcomes of haemoglobin levels, platelet counts, spleen and liver size, bone pain and liver function. However, this study found no evidence of a link between time spent on ERT and patient-reported physical or mental quality of life, as measured by the SF-36 and the EQ-5D in adults, and the PedsQL score in children.
We think this study has provided important information to guide clinical policies and to help people with the condition and their carers to make rational decisions about treatment options. It should be noted that these results add to, but do not supersede previously published studies on the effectiveness of ERT.
Once it is published, the full report, including copies of all data collection forms and quality of life questionnaires will be available from the HTA website at http://www.hta.ac.uk/research. Alternately, if you would like a copy of the full report, please contact the authors at and we will be happy to send you one.
We want to say a huge thank you to all the people
who took part as we could not have done this study without you.