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New study explores unique approach to treat a rare liver disease

Written by Louise Stanley on . Posted in Clinical trials, Experimental medicine.

A UK research study looking into a new approach to treat primary sclerosing cholangitis (PSC), a rare disease where the body’s immune attacks its own liver, has been given the green light thanks to vital funding from LifeArc and the patient-led organisation PSC Support.

The FARGO trial, led by Dr Palak Trivedi at the University of Birmingham, will find out if a new treatment can slow PSC progression and improve quality of life for patients.

What is PSC?

PSC is a rare liver disease which affects around 3,600 people in the UK. People can develop the condition at any age, but most commonly those under the age of 40.

In PSC, the body’s immune system attacks the liver, causing inflammation and scarring of the bile ducts. This causes bile to stop flowing properly, and patients experience repeated infections, develop liver failure and, in some cases, cancer. In four out of five people, the body’s immune system will also attack the bowel, leading to inflammatory bowel disease (IBD) as well as liver disease. The combination of PSC and IBD can lead to around a third of all patients developing bowel cancer and patients require a colonoscopy every year to screen for it.

Currently, doctors treat PSC by managing symptoms only. We don’t fully understand what causes PSC, and there is no cure. A liver transplant is the only life-saving treatment. Although a very rare disease, PSC accounts for 1 in 10 of all liver transplants in the UK and is now the leading reason for liver transplantation in several European countries.

While it is life saving, liver transplantation is also risky and costly to the NHS. People who have had a transplant must take a cocktail of drugs to prevent their new liver being rejected. PSC can still return in around a third of people who have had a liver transplant.

Imbalance of gut microorganisms – and a new approach

We know that the microbes present in the gut of people with PSC are different to those in people without liver and bowel inflammation. This gut microbe imbalance is linked with many abnormal immune functions, which may drive development of the condition.

In the FARGO study, the research team will find out if taking stools containing natural microbes from the gut of healthy donors, refining it in a lab, and transferring it to the bowel of people with PSC, could reverse the imbalance of gut microorganisms. This treatment is called faecal microbiota transplantation, or FMT. Early research has also shown that it can treat IBD.

Bespoke clinical trial

The Birmingham team, together with teams at the Royal Free London, St Mark’s Hospital, Imperial College London, and Norfolk and Norwich University Hospitals NHS Foundation Trust, will carry out a clinical trial to test this new treatment approach. People with PSC taking part in the study will receive either FMT once a week for eight weeks, or placebo (an inactive FMT equivalent). Each group will continue to receive their usual routine standard of care for their IBD.

The teams will observe both groups for another 40 weeks. The team will then measure how successful the treatment has been in improving liver blood tests, reduce scarring of the liver, lessen the severity of their IBD, and improving symptoms and quality of life.

Dr Palak, who is leading the trial at the NIHR Birmingham Biomedical Research Centre, said: “I am delighted that LifeArc has chosen to support such a novel, bespoke and distinctive clinical trial, and to enable us to the necessary ground work needed to better understand how PSC develops and progresses.

“This study will really help us to understand which gut microbes are most important, and how this potential treatment could be scaled up to treat more people.

“Our study will lay the foundation for future work on a larger scale, with a view to making FMT available across the world.

“Should our trial show that FMT works well, PSC Support will be advocating for patients to access FMT as early as possible. We hope this means it will be making a difference to patients within five years after we’ve completed this work.”

LifeArc’s Dr Catriona Crombie said: “Our approach to funding is to work with others, to uncover the potential of promising research that could solve complex healthcare problems that patients face.”

She continued: “We’re delighted to be jointly funding this project with PSC Support, where Dr Trivedi’s team aim to reveal more information about PSC and help to translate this experimental treatment, from lab idea towards the clinic, where it could offer hope to patients with PSC.”

Martine Walmsley, Chair of Trustees at PSC Support, said: “Although we welcome clinical trials that test brand new drugs for PSC, progress is painfully slow. People with PSC don’t have the luxury of time and we must look at quicker medicine development routes.”

Diabetes: Birmingham launches five new research studies

Written by Louise Stanley on . Posted in Clinical trials, Health inequalities, Inflammation and chronic disease.

BHP founder-member the University of Birmingham has announced the launch of five new major studies aimed at improving the prevention, treatment and management of type 1 diabetes – with a particular focus on children and young adults.

The new studies include:

  • The ELSA Study: Led by Professor Parth Narendran, the ELSA Study (EarLy Surveillance for Autoimmune diabetes) will see researchers interviewing families, doctors, nurses and schools, to determine if, and how, the UK should develop a testing and monitoring programme that will identify children at risk of type 1 diabetes. The ELSA Study is being funded by the National Institute for Health Research (NIHR), and is being carried out in collaboration with Birmingham Health Partners, Birmingham Community Healthcare NHS Foundation Trust and the Department of Health and Social Care, as well as the Universities of Cardiff, Warwick, Oxford and Imperial College London.
  • Diabetes and health inequalities: Through £1.9m funding from NIHR, Professor Tim Barrett’s team will ask children and young people with diabetes and their families from poorer and/ or ethnic minority backgrounds how language issues, feelings, income, living conditions and food availability affect how they manage diabetes. They will identify new ways to make diabetes management easier and more successful, and will test these systems in trials involving NHS hospitals.
  • Immunotherapies for diabetes: The greatest barrier to the development of specific immunotherapies for type 1 diabetes is that we currently do not understand the mechanism of how immunotherapies switch off the immune response to our own proteins. A clinical study led by Professor David Wraith, and funded by $735,000 from The Leona M. and Harry B. Helmsley Charitable Trust, will be carried out in collaboration with Cardiff University. It will test a new peptide developed by the University of Birmingham, work which was also funded by the Helmsley Charitable Trust with a $610,000 grant. The new peptide has the potential to control the T-cell immune response in people who are either at risk of developing type 1 diabetes or are newly diagnosed. In this study, the team will assess the changes in immune cells from the site of injection, the draining lymph nodes and peripheral blood. This will be the first in-depth analysis of the molecular changes responsible for antigen-specific immunotherapy in type 1 diabetes.
  • Sight loss and diabetes: Two separate projects led by Dr Jose Romero Hombrebueno will explore the function of membrane-bound cell organelles, known as mitochondria, which generate most of the chemical energy needed to power the cell’s biochemical reactions. The researchers will examine the role of mitochondrial function in both the development of multiple health conditions as the consequence of type 1 diabetes, and also the role it plays in developing diabetic retinopathy – an eye condition that can cause sight loss and blindness in people who have diabetes. The latter research is being funded by Diabetes UK, while the former is being funded by the European Foundation for the Study of Diabetes.
  • Exercise and type 1 diabetes: Led by Dr Alex Wadley and funded by the Rosetrees Trust, this research will examine how a home-based exercise programme impacts autoimmunity in patients with newly diagnosed type 1 diabetes. The project will evaluate whether exercise slows the progression of type 1 diabetes by altering the number and activity of white blood cells in the circulation that have the potential to attach to, enter and degrade the pancreas. Although evidence supports a role for exercise to promote general health and wellbeing in patients with type 1 diabetes, this project aims to provide novel evidence that exercise can directly slow the progression of the disease upon diagnosis.

Parth Narendran, Professor of Diabetes Medicine at the University of Birmingham’s Institute of Immunology and Immunotherapy, said: “The UK has one of the highest incidences of type 1 diabetes in the developed world, at 25 per 100,000 per year, and type 1 diabetes is the most common form of diabetes in children. It occurs when cells that make insulin don’t work as they should, and people with the condition have to self-inject insulin for their entire lives. Studies have recently shown that some medicines can safely delay people getting type 1 diabetes. Some countries, such as the US and Australia, already have surveillance systems to identify people at risk of developing type 1 diabetes and to offer them participation in prevention trials and also to reduce their chances of developing type 1 diabetes as an unexpected emergency. The UK does not have such a system in place. Until now, nobody in the UK has explored whether parents and children would welcome such a system, and how it would work. Through ELSA we will potentially be able to change NHS healthcare policy which would result in the early detection and prevention of this condition and its associated long-term complications.”

Timothy Barrett, Professor of Paediatrics and Child Health at the University of Birmingham’s Institute of Cancer and Genomic Sciences, said: “Diabetes causes high blood sugar levels, which can lead to eye and kidney damage if the condition is not well managed. We know that better sugar control reduces this risk, however, children with diabetes from poorer and/ or ethnic minority groups, often have worse sugar control, while these complications often develop when they are young adults who are working and starting families. There is little evidence to show any previous interventions have helped in reducing health inequalities for children with diabetes in different groups. We will work with young people, their families, and diabetes clinicians to develop an action plan that families feel comfortable with and that will support them to improve their self-management.”

Professor David Wraith, Director of the University of Birmingham’s Institute of Immunology and Immunotherapy, said: “Studies have shown that immunotherapies could play a vital role in treating type 1 diabetes, and it’s essential that we can develop new drugs that could specifically target cells that cause the body’s immune response to behave the wrong way in a person with type 1 diabetes. Our project will help improve our understanding of how the human body’s immune system responds to therapies, which in turn will help the development of new treatments.”

Dr Jose Romero Hombrebueno, Hale-Rudd Lecturer in Experimental Ophthalmology at the University of Birmingham’s Institute of Inflammation and Ageing, said: “It is estimated that 224 million people will have diabetic retinopathy and 70 million will have sight-threatening diabetic retinopathy by 2040. Nearly 90-95% of patients with type 1 diabetes and 78% with type 2 diabetes are expected to develop minimal retinal damage after having diabetes for more than 15 years. Therefore it’s essential that we carry our research that will help advance our knowledge of the underlying causes and potential ways to treat or prevent vision loss in those with diabetes.”

Dr Alex Wadley, of the University of Birmingham’s School of Sport, Exercise and Rehabilitation Sciences, said: “It’s estimated that around 70% of patients with type 1 diabetes do not meet the current recommended exercise guidelines of 150 minutes per week. We are using a home-based exercise programme, which has proven highly popular and safe for individuals with type 1 diabetes, to evaluate how regular exercise impacts the immune system of newly diagnosed patients. Type 1 diabetes is a disease where the body’s own white blood cells attack the pancreas and stop insulin production, resulting in high blood sugar. Regular participation in exercise is key to supporting health and wellbeing in people with type 1 diabetes, but we don’t know how exercise directly impacts these white blood cells that do the damage. With limited therapies available for patients currently, we hope that our findings can promote the use of exercise as an important lifestyle choice for patients and impact standard treatment approaches for type 1 diabetes nationally.’’

New clinical trial aims to improve heart protection during surgery in children

Written by Louise Stanley on . Posted in Clinical trials.

A new clinical trial being led by BHP founder-member the University of Birmingham and funded by the British Heart Foundation could help improve the recovery of children who undergo life-saving heart surgery.

The £570,000 study will compare two ways of protecting the heart when children require open heart surgery to repair congenital heart defects, to find which is most effective.

Congenital heart disease is a heart defect that develops in the womb before a baby is born. Each day in the UK, around 13 babies are diagnosed with a congenital heart condition, with more diagnoses later in life.

In severe cases, and often at a young age, open heart surgery is required to repair the defect to help improve the child’s survival and quality of life. Some children require multiple operations, and recovery from open heart surgery can take several weeks or even months.

During open heart surgery, a fluid called cardioplegia is commonly used to stop the heart beating so that the surgeon can repair it safely. Although the technique is safe, cardioplegia stops the blood flow to the heart and may cause damage to the heart muscle when the blood flow is restored, which can affect the child’s recovery.

There are many different types of cardioplegia solutions available, which work in slightly different ways – and it is not currently known which fluid works best in children of different ages.

In the United States, the most commonly used solution is called del Nido cardioplegia, which was designed specifically for use in children’s heart surgery but has not previously been available in the UK.

The new trial will compare del Nido cardioplegia with St Thomas’ cardioplegia, which has been used for many years in both adults and children and is currently the standard of care in the UK.

It will involve 220 children undergoing open heart surgery at four hospitals across the UK – Birmingham Children’s Hospital, Bristol Royal Hospital for Children, Great Ormond Street Hospital and Leeds Children’s Hospital.

Half of the patients will be assigned to receive del Nido, with the other half receiving St Thomas’ cardioplegia. Researchers will then compare the two groups by assessing how well the children recover from surgery and determining the extent of any heart damage.

The study will help to reveal whether one solution is potentially more effective than the other for children during surgery.

The research will be led by Nigel Drury, Consultant in Paediatric Cardiac Surgery at BHP member Birmingham Children’s Hospital and Hunterian Professor in the Institute of Cardiovascular Sciences at the University of Birmingham.

Mr Drury, who is also a British Heart Foundation (BHF) Intermediate Fellow, said: “By improving the way in which we protect the heart during surgery, we expect that children will recover from surgery faster and with fewer complications.

“These early benefits may also lead to better long-term outcomes, with less injury and scarring to the heart muscle. As children with severe heart defects often need multiple operations, they will have the most to gain from improving how we protect the heart during each surgery.

“If our trial is successful, this will support the need for a larger, definitive study, which could have the potential to change the way children are treated around the world.”

Dr Shannon Amoils, Senior Research Advisor at the British Heart Foundation, said: “Heart defects are the most common congenital anomaly in babies born in the UK, so it’s important that we continue to refine treatments for these conditions to help improve the lives of young patients.

“This multi-centre trial, held at four leading UK children’s hospitals, will compare how well these two solutions can protect the hearts of children undergoing open heart surgery. If the study reveals important differences between the two solutions, a larger clinical trial would be needed to further investigate the findings. Ultimately, this important research could result in heart surgery becoming even safer for children.

“The BHF can only fund vital research like this thanks to the generous support of the public, in driving forward our mission to beat heartbreak forever.”

Alfie Donnelly, aged nine and from Erdington, was born with various complex congenital heart diseases and has had to undergo three open heart surgeries at Birmingham Children’s Hospital.

Mum Claire Donnelly, aged 43, said: “When Alfie was a new-born, we noticed that he wasn’t feeding well, was cold all the time and wouldn’t cry. We struggled to wake him one morning and he was making a grunting noise when he was breathing, so I rang the hospital who told us to bring him in.

“Alfie became so ill that he was put on a life support machine. After several tests and scans, we were told that Alfie’s heart condition was rare and complex and that he needed open heart surgery. We were also told that if a procedure did go ahead, it was unlikely he would survive past his first birthday. The whole situation felt so bizarre, I remember feeling frozen to the spot.

“Alfie was just one week old when he had his first operation, and he was a little fighter. He has since had two more open heart surgeries, which included replacing the damaged valve in his heart with a donor valve.

“Alfie’s recovery after surgery has been slow and he has had further complications. Following his first and second surgery, Alfie had a build up of fluid in his lungs and this required several chest drains, which meant spending further time in hospital.

“With what Alfie has been through, it has made us a solid family and we all appreciate life even more. For us as a family, the research that the BHF is funding gives us hope that children and babies with congenital heart disease, like Alfie, aren’t being forgotten. So much more is needed to raise awareness of heart defects in children.”

Researchers awarded vital funding to explore treatment to slow rare liver disease

Written by Louise Stanley on . Posted in Clinical trials.

LifeArc and PSC Support have jointly awarded £948,774 for new research into primary sclerosing cholangitis (PSC) – a rare disease where the body attacks its own liver, causing inflammation and scarring of the bile ducts.

The national study, led by Dr Palak Trivedi at BHP founder-member the University of Birmingham, is called FAecal microbiota transplantation in primaRy sclerosinG chOlangitis: The FARGO trial. The aim of the study is to explore the potential of a new treatment to slow the progression of PSC and improve the quality of life for patients.

PSC is a rare liver disease where the body attacks itself, causing inflammation and scarring of the bile ducts and liver. This causes bile to stop flowing properly, leading to repeated infections, liver failure and, in some cases, cancer. In 80% of people with PSC the body will also attack the bowel, which can lead to inflammatory bowel disease (IBD).

The combination of the two conditions results in a 15-30% lifetime risk of bowel cancer, and patients require a colonoscopy every year to look for this complication. PSC affects approximately 3,600 people in the UK. The condition can develop at any age, but has a particular impact in people under 40 years.

At present, the treatment of PSC is focused on managing the symptoms, not treating the cause. Unfortunately, there is no cure, nor any medication that has been shown to improve survival. Liver transplantation is the only lifesaving treatment. Although a very rare disease, PSC accounts for 10-15% of all liver transplants performed in the UK and is now the leading reason for transplantation in several European countries.

Transplantation is risky and costs around £1m per patient (including aftercare). Moreover, PSC returns in around 30% of people who have had a liver transplant.

The team, led by researchers at the University of Birmingham, has one of the largest PSC research programmes globally, with a dedicated PSC-IBD clinic as part of the Centre for Rare Diseases. The research team is partnering with PSC Support, the leading patient organisation for people living with primary sclerosing cholangitis, which has a wealth of experience working with medicines’ regulators on drug development for this condition.

Through this partnership the team aims to explore the potential of a new treatment to slow the progression of PSC and improve the quality of life for patients.

It has been shown that the makeup of gut microorganisms in PSC are different to that found in people without liver and bowel inflammation, and that this is associated with many abnormal immune functions, which may be a driver of disease development. The Birmingham research team will trial a novel treatment called faecal microbiota transplantation (FMT), which involves taking stool from the gut of healthy donors, refining it in a laboratory, and transferring contents to the bowel of people with PSC to reverse the imbalance of gut microorganisms.

Early research has shown that FMT is effective and safe in treating IBD. This grant, which is jointly awarded by the LifeArc philanthropic fund and PSC Support, will enable the team to accelerate and scale up their research to answer the key questions that will allow them to translate this experimental treatment, from idea to direct patient benefit across the UK PSC population.

Dr Trivedi, Associate Professor and Consultant Hepatologist at the NIHR Birmingham BRC said: “LifeArc is a self-financing charity that advances promising life science ideas into life-changing solutions for patients, particularly those living with a rare disease. I am delighted that they have chosen to support such a novel, bespoke and distinctive clinical trial, alongside the necessary translational work needed to better understand how PSC develops and progresses.

“We will test the safety and long-term effects of FMT to treat people with PSC. In parallel, this study will really help us to understand which specific consortia of gut microbes are most important, and how this information can be used to enhance the product for large scale rollout.”

Researchers will randomly allocate individuals with PSC to receive either FMT once a week for 8 weeks (group 1), or placebo (an inactive FMT equivalent; group 2). Each group will continue to receive routine standard of care for symptoms and treatment for their IBD.

Both groups will be observed for another 40 weeks, meaning the trial will run for 48 weeks. The team will then measure how successful the treatment has been in improving liver blood test results, the burden of scarring in the liver, activity of IBD and quality of life.

“Our study will lay the foundation for future work on a larger scale, with a view to making FMT available on a more global scale,” added Dr Trivedi. “In parallel, PSC Support will work with the wider study team, to support delivery of FMT as a treatment after the trial has finished.

“This will include writing and submitting the necessary trial documents to the UK medicines’ regulatory agency (the MHRA), which is a necessary step to broaden access to new treatments for people living with the disease.

“Should our trial deliver a positive efficacy signal, then PSC Support are ready to lead the conversation and advocate for patients to access FMT as early as possible. We expect patient benefit within 5-7 years after completion of this work and are working with the University of Birmingham Enterprise and Drug Discovery teams to achieve this goal.”

Birmingham research shapes new miscarriage guidelines

Written by Louise Stanley on . Posted in Clinical trials, Maternal health.

Research led by BHP founder-member the University of Birmingham has helped to shape guidelines which could mean thousands of women with prior miscarriage, and bleeding in early pregnancy, could be eligible for treatment with progesterone each year.

The updated guidance, announced today by the National Institute for Health and Care Excellence (NICE), follows a review of evidence by NICE’s independent guideline committee. The key evidence came from two trials – PRISM and PROMISE – led by the University of Birmingham in collaboration with Tommy’s National Centre for Miscarriage Research.

The results of the clinical trials, published in January 2020, evidenced both the clinical and economic advantages of giving a course of self-administered twice daily progesterone pessaries to women with prior miscarriage from when they first present with early pregnancy bleeding up until 16 weeks of pregnancy. In such women, the treatment reduces miscarriage risk and increases livebirth chances.

NICE’s updated guidance – ‘Ectopic pregnancy and miscarriage: diagnosis and initial management’ – recommends offering progesterone to women who have early pregnancy bleeding and who have previously had a miscarriage.  An ultrasound scan should be performed in these women, and if a fetal heartbeat is confirmed, NICE’s new guidelines recommend treatment with progesterone should continue until 16 weeks of pregnancy have been completed.  NICE’s independent guideline committee found that there was no evidence of benefit in women with early pregnancy bleeding but no previous miscarriage, nor in women with previous miscarriage but no early pregnancy bleeding in the current pregnancy.

Progesterone is a hormone that is naturally secreted by the ovaries and placenta in early pregnancy and is vital to the attainment and maintenance of healthy pregnancies.

PROMISE studied 836 women with unexplained recurrent miscarriages at 45 hospitals in the UK and the Netherlands, and found a 3% higher live birth rate with progesterone, but with substantial statistical uncertainty.

PRISM studied 4,153 women with early pregnancy bleeding at 48 hospitals in the UK and found there was a 5% increase in the number of babies born to those who were given progesterone who had previously had one or more miscarriages compared to those given a placebo. The benefit was even greater for the women who had previous ‘recurrent miscarriages’ (i.e., three or more miscarriages) – with a 15% increase in the live birth rate in the progesterone group compared to the placebo group.

Of the newly updated NICE guidance, Arri Coomarasamy, Professor of Gynaecology & Reproductive Medicine at the University of Birmingham and Director of Tommy’s National Centre for Miscarriage Research who led the PRISM and PROMISE trials, said: “After many years researching the use of progesterone and working to make treatment more accessible, today’s new miscarriage care guidelines from NICE include a very welcome change. Our research has shown that progesterone is an effective and safe treatment option, which could prevent 8,450 miscarriages a year in the UK – but we know it’s not yet reaching everyone who might benefit. This recommendation from NICE is an important step in tackling the current variation in miscarriage services across the country and preventing these losses wherever possible.”

Tommy’s CEO Jane Brewin said: “It’s great to see NICE taking our progesterone research on board in their new miscarriage care guidelines, which will help save babies’ lives and spare parents’ heartache. Miscarriage is often dismissed as ‘one of those things’ we can’t do anything about – even by some healthcare professionals, who may not specialise in this area to know the latest evidence. We hear from women who were denied progesterone treatment when they should have been eligible, simply because their doctor wasn’t familiar with it, so we hope NICE’s recommendation will help end some of these inequalities in miscarriage care that add more pain to an already unbearable experience.”

Meanwhile, Professor Coomarasamy was among the leading authors to lay bare the devastating impact of miscarriage and set out a raft of recommendations to improve treatment and care in a series of three research papers published in The Lancet in April 2021.

Amongst the calls to action by the research team was for urgent changes to NHS policy, which currently provides exploratory testing for underlying causes of miscarriage for women only after they have experienced three consecutive miscarriages.  The team says many of the risks related to a miscarriage are present even after one or two miscarriages, and appropriate care should be provided to all women who have experienced one or more miscarriages.

The Lancet ‘Miscarriage Matters’ series of papers formed part of a campaign by charity Tommy’s, including a petition to improve miscarriage care which has been signed by almost 230,000 supporters.

Tommy’s National Centre for Miscarriage Research has also been working with the Royal College of Obstetricians and Gynaecologists (RCOG) to share the knowledge and recommendations from The Lancet research.  Now, RCOG has updated its miscarriage care guidelines taking The Lancet papers on board and encourages the NHS to adopt a graded model of care so that parents can get support after every loss and earlier access to specialist tests and treatments.

In the revised guidelines, RCOG suggest that ‘recurrent miscarriage’ should be redefined so that losses don’t have to happen in a row for parents to receive support. Instead, they encourage doctors to use their discretion after two miscarriages if they suspect an issue might be causing the losses, and state that non-consecutive losses or those with different partners should still be treated as recurrent miscarriage.

Meanwhile, in June this year Olivia Blake MP delivered Tommy’s petition to an Adjournment Debate in Parliament in support of the campaign, which led to the then Minister for Mental Health, Suicide Prevention and Patient Safety, Nadine Dorries MP, announcing that the Government would incorporate a number of the recommendations into the Women’s Health Strategy which will aim to improve the health and wellbeing of women across the country.

Since then, Tommy’s CEO Jane Brewin has written a joint letter with Olivia Blake to new Health Minister Gillian Keegan MP, asking her to uphold Nadine Dorries’ promises in Parliament and meet with Tommy’s to discuss what happens next to make good miscarriage care widely and fairly available for everyone.

Professor Coomarasamy said: “As we work to open the ‘black box’ of miscarriage in the hope of unpicking its causes and finding new therapies, the UK must change its approach to miscarriage care, not only to reduce the risk wherever possible but also to better support those who do tragically lose their babies.”

Tommy’s CEO Jane Brewin said: “The right care can reduce the risk of miscarriage, and the right support can help parents if they experience loss – but that help isn’t reaching everyone across the UK after every miscarriage; this can and must change.

“It’s great to see the Royal College taking forward Tommy’s recommendations from our Lancet research in their new care guidelines, so we can prevent more losses wherever possible but also better support those who do sadly lose their babies. We know what to do and how to do it, so now we need a commitment across the NHS to develop these care pathways and improve support for everyone.”

In addition to the recommendations on tests and treatments for miscarriage, RCOG has also highlighted where research and evidence is lacking. This includes the health disparities facing women from Black, Asian or minority ethnic backgrounds, who were found to be at higher risk of having a miscarriage than White women in The Lancet research series. Researchers at the University of Birmingham have already begun work in this area, in partnership with Tommy’s National Centre for Miscarriage Research.

An estimated 23 million miscarriages occur every year worldwide – equating to 44 pregnancy losses each minute.  Miscarriage (defined as the loss of a pregnancy before 24 weeks) costs the UK at least £471 million a year due to direct impact on health services and lost productivity. However, scientists expect costs surpass £1 billion per year when factoring in longer-term physical, reproductive and mental health impacts.

New drug treatment regimen shows promise for patients with lupus

Written by Louise Stanley on . Posted in Clinical trials, Inflammation and chronic disease.

The results of a randomised controlled trial, published in Annals of Internal Medicine, found that a new drug treatment regimen – using belimumab soon after rituximab – reduced a disease-related autoantibody and severe disease flares in lupus patients.

Systemic lupus erythematosus (SLE or lupus) is a long-term autoimmune condition, causing a variety of problems including joint pain, skin rashes, kidney disease and tiredness. While there is no known cure for this debilitating disease, the BEAT-Lupus clinical trial found that the combination of belimumab and rituximab shows promising results; reducing severe lupus flares by 3-fold for patients who had persistent, severe lupus disease requiring rituximab therapy at the beginning of the study.

Senior author Professor Caroline Gordon, Emeritus Professor of Rheumatology and member of the Institute of Inflammation and Ageing’s Rheumatology Research Group, together with colleagues from University College London conducted a phase 2 randomised trial involving 52 patients with SLE that was refractory to conventional treatment and whose physicians had recommended rituximab therapy. Patients were treated with rituximab and then randomly assigned four to eight weeks later to receive intravenous belimumab or placebo for 52 weeks.

The researchers found that IgG anti-dsDNA antibody levels were lower in belimumab-treated patients at 52 weeks compared with placebo-treated patients (geometric mean, 47 versus 103 IU/mL; 70% greater reduction from baseline). The risk for severe flare was reduced significantly with belimumab versus placebo (hazard ratio, 0.27), with three and 10 severe flares in the belimumab and placebo groups, respectively. There was no increase seen in the incidence of serious adverse events in the belimumab group.

Professor Michael Ehrenstein, Chief Investigator of the BEAT-Lupus trial, said: “Thanks to the dedication of the lupus teams at participating hospitals we are delighted to not only have completed recruitment, but also to provide preliminary evidence for a clinical benefit of the combination of rituximab and belimumab, compared to patients treated with rituximab alone.”

“These findings support further exploration of belimumab after rituximab as the first combination biologic therapy for patients with SLE, at least in those whose disease is refractory to conventional therapy and/or requires high corticosteroid dosages,” the authors write.

Professor Gordon previously pioneered the methodology for assessing lupus disease activity and flares using the BILAG-2004 index. The main secondary clinical outcome of reduction of severe lupus flare in the BEAT-Lupus trial was based on this work, and flare was defined using this index.

She explained: “We were delighted to find that this treatment regimen not only reduced disease causing autoantibodies but also reduced severe flares which cause very distressing symptoms and disruption to patients’ lives. This study offers the hope that this combination of drugs will be useful in the future if the results are confirmed in a larger trial.”

The study was funded primarily by Versus Arthritis; GlaxoSmithKline provided belimumab free of charge, as well as some additional funding.