Doctors are treating patients with autoimmune diseases like Crohn’s and lupus “blind”—unable to tell who will need aggressive therapy and who will recover with minimal care. Between 5 and 10% of people will develop such a condition, yet clinicians have no way to predict a patient’s course. This forces a dangerous gamble: either delay intensive treatment until the disease visibly worsens, or give powerful drugs to everyone early, exposing many to unnecessary side-effects and wasting NHS resources. This programme uses genomic technology to measure gene expression in patients’ blood white cells before and after treatment. Advanced computational analysis will identify patient subgroups invisible to standard clinical exams, and link those subgroups to different outcomes. The team has already discovered a biomarker that predicts outcomes in four conditions—including inflammatory bowel disease, lupus, and vasculitis—and that test is now entering clinical trials. If successful, this work could turn a blind treatment system into a targeted one. Doctors would know from the start which patients need intensive therapy and which do not, reducing side-effects, cutting waste, and improving care for millions.
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Between 5 and 10% of the population will develop an autoimmune or inflammatory disease at some point during their lifetime. These diseases behave differently from person to person, with some people having an aggressive course while others have a more benign disease. When such diseases develop doctors need to treat them "blind" - as they have no way of predicting which patients have naturally benign disease, requiring only minimal treatment, and those who will require more intensive treatment to obtain control. This is a major problem for patients and for the healthcare system. It means that patients who need intensive therapy often find that this needs to be delayed until their disease progresses and the need for such therapy becomes obvious. Conversely, the early indiscriminate use of treatment for these diseases may mean that those who would do well without such treatment receive it unnecessarily, exposing them to significant side-effects. Such poorly targeted use of treatments also wastes limited NHS resources. We will use cutting-edge "genomic" technology to measure the genes expressed in blood white cells in patients with a number of diseases before and after treatment. Analysing this gene expression data using advanced computational techniques will allow us to identify subsets of patients that would not be apparent using conventional clinical assessment, and to determine if these subsets are associated with different disease outcomes. Additional tests which can be developed based on these observations might allow early diagnosis of patients with rare diseases, or be used to measure the degree of disease activity. We have proven that such an approach works, having recently discovered a biomarker that predicts outcome in four different conditions, including inflammatory bowel disease (Crohn's disease and ulcerative colitis), lupus and vasculitis - this is now entering clinical trials. The proposed programme will complete the analysis of a large study established in these four patient groups over the last ten years, and continue and extend the study over the next five years, allowing the use of recent advances in technology and the inclusion of additional diseases, such as AIH, EGPA/Churg Strauss and multiple sclerosis.
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