A groundbreaking blood test could revolutionize treatment for patients with lupus who don't respond to conventional therapies, according to researchers at University College London (UCL). The test identifies specific biomarkers that may predict which patients would benefit from an innovative combination of existing medications.
The £1.7 million clinical trial, named "Stratify Lupus," will evaluate whether patients with treatment-resistant lupus who test positive for a specific biomarker respond better to a combination therapy of rituximab and belimumab compared to placebo. The study is set to begin in spring 2026 across 16 UK hospitals, with results expected by 2029.
Precision Medicine Approach for Treatment-Resistant Lupus
Professor Michael Ehrenstein, consultant rheumatologist at University College London Hospitals and lead researcher, explained: "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."
Previous research by Prof. Ehrenstein's team identified a biomarker called IgA2 anti-dsDNA in approximately half of lupus patients who didn't respond to conventional treatments. Patients with this biomarker were found to be 17 times more likely to respond to the combination of rituximab and belimumab compared to rituximab alone.
Both medications are currently available on the NHS as individual treatment options for lupus but are not prescribed in combination. These targeted therapies are monoclonal antibodies—laboratory-produced copies of antibodies that the immune system naturally produces to fight infections.
Understanding Lupus and Current Treatment Challenges
Lupus is a chronic autoimmune condition affecting an estimated 69,000 people in the UK. The disease occurs when the body's immune system mistakenly attacks healthy tissues and organs, causing symptoms ranging from joint pain and skin problems to severe fatigue and inflammation of major organs.
The condition disproportionately affects women, particularly those of African, Caribbean, and Asian descent. Current treatments typically involve lifelong medication regimens, including steroids, immunosuppressants, and biological medicines, but many patients continue to experience symptoms despite these interventions.
Potential for Global Impact
"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," Prof. Ehrenstein noted. "Everyone talks about personalised medicine, but so far this goal has not been achieved in inflammatory/autoimmune rheumatic diseases. Stratify Lupus will be the first biomarker enrichment trial for lupus, which is a real coup for UK research."
The study is being funded by the charity Versus Arthritis and the Efficacy and Mechanism Evaluation (EME) Programme, a partnership between the National Institute for Health and Care Research (NIHR) and the Medical Research Council (MRC).
Professor Lucy Donaldson, director of research at Versus Arthritis, emphasized the significance of the trial: "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."
Trial Design and Methodology
The Stratify Lupus trial will focus specifically on patients whose lupus has not responded adequately to conventional therapies such as steroids or immune suppressants. Researchers will test participants' blood for the IgA2 anti-dsDNA biomarker, and those testing positive will be randomized to receive either the combination therapy of rituximab and belimumab or a placebo.
This approach represents a significant advancement in the field of rheumatology, potentially establishing a model for personalized medicine in autoimmune conditions. If successful, the trial could lead to more targeted and effective treatments for a condition that has historically been challenging to manage, particularly in its more severe forms.
