Head of “Living With”, Mariel Metcalfe and Associate Director Beth Clark, discuss the nature of Anaemia in CKD, treatment options and unmet patient needs.
Anaemia is a highly impactful condition that affects around 15% of patients with Chronic Kidney Disease (CKD) in the US, increasing up to around 50% of patients with later (stage 5) CKD. Research Partnership has explored the impact of this condition from the patient’s perspective through the “Living with Anaemia in CKD” study, with results available in a syndicated report exploring the patient journey, key unmet needs and desires for future treatments.
Behind the condition
Chronic Kidney Disease (CKD) describes the gradual loss of kidney function over time. It can be caused by a number of different conditions: most frequently diabetes and high blood pressure, but also some rarer conditions such as Glomerulonephritis (inflammation of the kidney's filtering units), inherited polycystic kidney disease or kidney infections. It is estimated that CKD affects as many as 1 in 10 people worldwide at some point in their lives, and more commonly affects women and people of South Asian or African heritage. Patients with CKD often experience other conditions and complications, such as high blood pressure, lower bone density, and anaemia because of insufficient kidney function.
Anaemia is a reduction in the total number of circulating red blood cells (RBC), resulting in a reduced haemoglobin concentration. One of the key functions of the kidney is in erythropoiesis, the process through which red blood cells are produced. Healthy kidneys produce a molecule called erythropoietin (EPO), which stimulates RBC production. When kidney function declines in patients with CKD, EPO production slows down, which results in a depletion of RBCs and ultimately a reduced oxygen supply to other key organs. This causes the typical symptoms of anaemia such as fatigue, rapid heart rate, breathlessness, pale skin, difficulties with appetite and sleep, dizziness and headaches.
Current treatment of anaemia in CKD & unmet needs
Current treatments for anaemia in CKD include erythropoiesis stimulating agents (ESAs), to help re-stimulate RBC production, as well as iron supplementation through pills or IV administration. A minority of patients require blood transfusions when first diagnosed with anaemia, as a faster means of increasing very low haemoglobin levels.
ESA use is somewhat limited by safety concerns with cardiovascular risks, so while effective, only a minority of patients are able to benefit from this class of drug. Based on the “Living with Anaemia in CKD” report, patients on dialysis are more satisfied with their anaemia treatment overall, as iron and ESAs are typically added, which is more convenient for them versus taking additional medication. Patients on dialysis are also less aware of any side effects of iron or ESAs, as their treatments are administered simultaneously and there is less differentiation between anaemia treatments versus general CKD treatment.
For patients not on dialysis, satisfaction with iron supplements is generally low, particularly towards iron pills, due to the unpleasant taste and gastroenterological side effects; however, injections are also often unappealing to patients. Unmet needs therefore exist for oral treatments with improved efficacy and fewer unpleasant side effects.
Patient feelings towards anaemia
Anaemia inevitably has a strong impact on patients’ quality of life, largely due to the physical impact of extreme fatigue, reported as the most bothersome symptom by 50% of patients in the US and 35% of patients in EU. Anaemia symptoms such as fatigue, dizziness and difficulty sleeping limit patients’ ability to carry out day-to-day activities, work and make social plans.
“I don't have any motivation to do anything. I'm usually someone who is quite restless and always has to be moving and has difficulty sleeping. Now I could literally sleep all the time. I have to force myself to get out of bed and to get through daily life.” Stage 3 CKD Patient, Germany
The negative emotional ramifications of the disease can affect patients and their loved ones or carers due to such depleted energy levels. Despite this significant impact of anaemia, around 50% of patients lack a detailed understanding of their condition and how their haemoglobin levels relate to their symptoms.
There is some confusion and a lack of differentiation between anaemia and CKD among patients, particularly in terms of whether certain symptoms are a direct result of anaemia, or a more general symptom of CKD. Anaemia can take a back seat in terms of patient and physician priorities, compared to managing the kidney problems and other urgent issues such as blood pressure. This can lead to a lack of understanding among patients and ultimately impact how seriously they take their anaemia treatment, leading to less than perfect compliance, particularly with iron pills. Patients who are on dialysis for their CKD in particular can lack awareness of their anaemia and its treatment, as the treatment for anaemia is merged with dialysis and not always thought of as a separate issue that requires attention.
How pharma can help – Novel treatments and more
A new class of drugs called hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors in development are predicted to have a considerable impact in the coming years. They work by mimicking the body’s natural response to low oxygen levels, stimulating erythropoiesis and regulating iron metabolism. Clinical trial results suggest greater efficacy in increasing haemoglobin levels and acceptable safety profile so far. At the publication of this article, the first HIF prolyl hydroxylase inhibitor to market, roxadustat, has already cleared Phase 3 trials and is approved in China and Japan, with reviews underway in the US and Europe. A number of other drugs within this class are in development and expected to come to market in the coming years.
As well as the development and promotion of novel treatments, many patients would benefit from additional support and education from pharmaceutical companies. Often, anaemia is discussed with the patient once when they are first diagnosed, and then can be deprioritised for some time. Patients desire more information about how anaemia links to their CKD, and specific advice on how to manage their symptoms. Awareness regarding the serious consequences of not properly treating their anaemia needs to be communicated clearly to patients, to help them perceive anaemia as a separate medical issue. This can help patients and doctors have more effective conversations about anaemia, ensure it is managed optimally and reduce the impact on their quality of life.
About the study: Living with Anaemia in CKD
“Living with Anaemia in CKD” is a syndicated report produced by Research Partnership, which offers valuable insights into patient attitudes and behaviour. The EU study was conducted amongst 81 CKD patients with anaemia in France, Germany, Italy and Spain. The US study was conducted with 51 CKD patients with anaemia. For both studies the methodologies consisted of 30-minute quantitative online interviews and a small sample of 30-minute qualitative add-on telephone interviews, with both patients and caregivers. Both samples were made up of a mix of stage 3-5 patients, and over 60% of both samples were patients receiving dialysis for their CKD.
The reports enable pharmaceutical companies to gain an in-depth understanding of the patient journey, from diagnosis through to ongoing management and the key challenges patients face with managing their anaemia and CKD. Through these reports, you will understand how these conditions impact patients’ lives physically and emotionally, what their level of understanding is about their condition and what unmet needs patients have related to its treatment and overall management of anaemia and CKD.