Sheffield Teaching Hospitals NHS Foundation Trust has become the only site in the UK to open a groundbreaking international trial which could revolutionise care for people living with a rare and degenerative disease that causes hardening and tightening of the skin and connective tissues.
The trial, called ‘UPSIDE’, is the first to test if autologous haematopoietic stem cell transplantation (a type of transplant involving the collection, storage and reinfusion of a patient’s own stem cells following high-dose chemotherapy) should be offered as a first-line treatment for patients with diffuse cutaneous systemic sclerosis. The trial is running across 11 European sites, with Sheffield the only UK national centre involved.
Diffuse cutaneous systemic sclerosis is a severe and incurable form of scleroderma, where the immune system attacks healthy tissue in the body, limiting mobility and causing skin hardening, inflammation and discoloration. Its progressive nature often results in significant organ damage, particularly to the heart, kidneys and lungs, shortened survival and reduced quality of life.
Current therapies rely on immunosuppressive treatments to control damage to skin and lungs. However, autologous haematopoietic stem cell transplantation has been shown to be more effective in more advanced patients who have failed other treatments, improving survival and quality of life whilst also leading to less widespread skin and lung deterioration.
Researchers also believe that giving stem cell transplantation for systemic sclerosis early in the disease could lead to fewer side effects and reduce risks associated with the intensity of the treatment. It may also be more effective at this early stage rather than later on.
Now UPSIDE is set to test this on 60 patients by comparing upfront autologous haemopoietic stem cell transplantation with immunosuppressive therapy (intravenous cyclophosphamide pulse therapy followed by mycophenolate mofetil) with rescue HSCT in case of treatment failure.
Cheryl Iddon, 53, of Warrington, received a stem cell transplantation for systemic sclerosis after being diagnosed with severe diffuse cutaneous systemic sclerosis in May 2021 shortly after celebrating her 50th birthday.
The transplant, which took place outside of the trial in September 2022, has led to huge improvements in the quality of her life, and reversed painful and disabling severity of the condition including flaky, itchy skin which has started to harden.
She said: “I would recommend this treatment to anyone who was in the position I was in. I’ve always been fit and healthy so to be diagnosed with a terminal illness just as I was turning 50 was devastating. It was a big unknown. I couldn’t get out of the bath or down the stairs. Now I can move about with much less pain. It’s improved my skin dramatically; and I’m almost back to where I should be. The care I received has been phenomenal. Having this treatment is one of the best things I’ve ever done. Without it, I might not be alive.”
Professor John Snowden, Professor of Haematology and Honorary Consultant Haematologist at Sheffield Teaching Hospitals NHS Foundation Trust, said: “We are delighted to have opened as the sole UK national site for this large international trial. Stem cell transplantation has shown promise as an effective, evolving treatment for this rare rheumatological condition. As one of the country’s leading centres in autologous haemopoietic stem cell transplantation, and the pioneers of this technique in certain multiple sclerosis patients, we hope to use our expertise to make a significant contribution to this trial and alter the trajectory of people living with this highly disabling and unpleasant condition by modifying disease course and delivering safe, improved outcomes.”
Dr Mohammed Akil, Consultant Rheumatologist at Sheffield Teaching Hospitals NHS Foundation Trust and UK Chief Investigator of the trial, said: “We are very excited to be part of this European study. Diffuse systemic sclerosis can progress rapidly and dramatically reduce quality of life. While immunosuppressive drugs can help, outcome remains poor in a large proportion of patients. Previous studies have suggested that stem cell transplant may halt disease progression. This is the first time the approach will be tested in an early stage randomised clinical trial.”
Eligible patients aged 18 to 65 who have not had the condition for longer than three years will be randomly allocated into either the transplant or immunosuppressive arm of the trial.
Patients involved in the trial will be followed up over the course of five years, with various outcomes such as survival, skin score and lung function, side effects, heart function, quality of life, hand mobility and daily functioning measured in both arms to compare and assess effectiveness of treatments. All check-ups and follow-ups will be given in line with usual care, meaning patients on the trial will not have to come into hospital more often when taking part in the trial.
Patients interested in joining the trial should discuss this first with their rheumatologist. They can also refer their doctor to the trial website (www.upsidetrial.com) for more information about the study.
The trial is being led by the University Medical Center Utrecht (Netherlands).
