More than 3,000 people, mainly women, are diagnosed with lupus (systemic lupus erythematosus, SLE) in the UK every year. The disease is an incurable and potentially life-threatening autoimmune condition that can cause the body’s immune system to attack its major organs. Characterised by arthritis, skin rashes, chronic fatigue and kidney problems, lupus predominantly affects women of child-bearing age, with Afro-Caribbean women most severely affected.
The trial team have developed a biomarker that can be detected in the blood of patients who are resistant to conventional treatments, which tells clinicians that they are 17 times more likely to respond to an innovative combination of drugs. The drugs are currently used in the NHS to treat lupus, but not at the same time.
The £1.7m STRATIFY Lupus trial is being funded by charity Versus Arthritis and the National Institute for Health and Care Research (NIHR). Professor Michael Ehrenstein from UCL Division of Medicine and a consultant rheumatologist at UCLH will lead the trial, which is due to begin in spring 2026.
Preparations at 16 trial sites across the UK will begin in June 2025, with patient recruitment through lupus centres to commence in the first quarter of 2026. The trial is scheduled to complete in 2029, with analysis completed by the end of that year.
Professor Lucy Donaldson, Director of Research at Versus Arthritis, which funds research and provides support services to those living with arthritis and musculoskeletal conditions, said: "This major trial holds real promise of a better future for those living with lupus, which particularly affects underserved people. Too few advances have been made in tackling the devastating disease which mainly affects women, in particular women of African and Caribbean heritage, in the prime of their lives."
Professor Ehrenstein and his team have dedicated many years to advancing lupus research, on which the latest trial will build. The team’s 2021 study BEAT Lupus found the combination of two advanced immune-system targeting ’biologic’ drugs, rituximab and belimumab, was able to bring disease activity under control and significantly reduce severe flare-ups in some (but not all) patients.
Further laboratory work and advanced analysis methods revealed the new biomarker in the blood - an antibody called IgA2 anti-dsDNA - was found in around 50% of lupus patients resistant to conventional therapy. The team tested blood samples from their own and a US trial and found those who tested positive for the biomarker were 17 times more likely to respond to the combination of rituximab and belimumab, compared to rituximab alone.
Now the team are undertaking an innovative trial where only patients positive for the biomarker will be given the drug combination. If the clinical trial proves successful, patients may not have long to wait to access the new targeted treatment.
Professor Ehrenstein said: "If the results are positive then we would apply to allow patients who are positive for the biomarker to receive the combination therapy on the NHS. Targeting the patients most likely to benefit from this treatment should make it deliverable on the NHS and improve patient access and outcomes."
Those living with lupus can testify to the challenges of finding treatments that work. Ayo Ogunwumiju was pregnant when she began experiencing shortness of breath, chest pains and fatigue. Initially put down to pregnancy-related complications, Ayo’s symptoms progressed and by the time her daughter reached the age of six months she was struggling to lift her baby due to intense joint pain.
"I was eventually diagnosed with lupus after being hospitalised when I lost mobility in my legs and found it difficult to breathe," recalled Ayo, who has tried many treatments over the years to bring her symptoms under control.
"It took me six years of trying different medications with horrible skin blisters that left me with scars before I was finally put on a treatment that works well for my immune system. Research like this, using a biomarker in the blood to target better treatments to control people’s symptoms, would make a world of difference to patients not having to live in pain for a long period of time."
In terms of achievement, a successful trial would not only improve lives of patients but herald a breakthrough in advancing research that aims to deliver personalised medicine - something written into the future direction of the NHS.
Professor Ehrenstein said: "To have a positive result in a personalised medicine trial for lupus would be globally significant, not only for the biomarker and treatment combination, but also the success of this targeted approach. Everyone talks about personalised medicine, but so far this goal has not been achieved in inflammatory or autoimmune rheumatic diseases. STRATIFY Lupus will be the first biomarker enrichment trial for lupus, which is a real coup for UK research."
Professor John Simpson, NIHR Director of the Efficacy and Mechanism Evaluation Programme, said: "This innovative trial heralds an important shift towards specifically delivering treatments tailored to patients who are most likely to benefit. This raises the real potential to open up future effective treatment options for people with systemic lupus erythematosus, many of whom have limited effective treatment options. It has been a pleasure to partner strategically with Versus Arthritis to make this important trial happen."
The trial, and supporting studies, have been aided by Lupus UK, UCLH/UCL Joint Research Office, and GlaxoSmithKline.
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Mark Greaves
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