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Two large multicentre clinical trials designed and led by researchers and clinicians in Leeds have resulted in major changes to treatment for patients with multiple myeloma. Myeloma VII clearly established the use of high-dose melphalan supported by autologous stem cell transplant (ASCT) following chemotherapy. Myeloma IX, the largest randomised controlled trial ever in myeloma, showed that zoledronic acid, in addition to reducing skeletal damage, showed an overall survival benefit and introduced the use of thalidomide as an effective yet less toxic therapy. Adoption of these treatment regimens has produced significantly improved outcomes throughout the developed world.
Research in Leeds led by Professor Paul Emery pioneered early diagnosis and treatment for patients with rheumatoid arthritis (RA), with the aim of disease remission rather than reduction of symptoms. This approach has transformed management of RA and is now standard practice for patients worldwide. It has led to greatly improved disease control, increased quality of life and reduced disability as well as direct productivity gains of an estimated £4 million per year to the UK economy.
The Acute Infarct Ramipril Efficacy (AIRE) multicentre international trial, conceived, designed, led and coordinated by Leeds was the first to show that use of early angiotensin converting enzyme Inhibitor (ACEI) therapy in patients with signs and symptoms of heart failure after an acute myocardial infarction (AMI) is associated with significantly longer survival and better quality of life. Further Leeds research showed the beneficial effects persisted long-term. The strategy of early initiation of ACEI is now a fundamental and routine part of the management of patients after AMI and has contributed to better survival and quality of life for patients around the world.
Research at the University of Nottingham has defined the clinical phenotype and management of lymphangioleiomyomatosis, a rare and often fatal multisystem disease affecting 1 in 200,000 women worldwide. The group has led the development and evaluation of new therapies and diagnostic strategies which are now part of routine clinical care. The research has underpinned the transformation of this previously under recognised and untreatable disease into a condition recognised by respiratory physicians, with international clinical guidelines, patient registries, clinical trials, specific treatments and a UK specialist clinical service.
Colorectal cancer is a common disease, which frequently causes death or morbidity, either because of failure to control the primary tumour or failure to prevent distant metastases. Leeds researchers have devised new treatment approaches using chemotherapy and radiotherapy and tested them in large randomised controlled trials which have led to major changes in clinical practice in the management of rectal cancer and advanced colorectal cancer (aCRC), driving clinical decision-making and improving outcomes for patients. This includes better-evidenced treatment for elderly patients and patient stratification on the basis of molecular biomarkers.
Researchers at the University of Manchester (UoM) have made a significant impact nationally and internationally on improving the outcome for children with acute lymphoblastic leukaemia (ALL) (~450 pa in the UK). The changes in clinical practice based on our research are now national standards of care for children with de novo and relapsed ALL in the UK and Ireland. Other international groups have adopted key findings from the results of our frontline trials. Our relapse protocol for childhood ALL underpins European and North American strategy for the management of relapsed disease.
Since 1998 the University of Leeds has developed the Leeds Foot and Ankle STudies in Rheumatology (FASTER) programme — to drive improvements in UK musculoskeletal foot care services. Results from FASTER clinical trials and a national survey of podiatry services directly informed NICE guidelines on foot care in arthritis. FASTER's research also provided key evidence for a national consensus on standards of care and aided a shift in the treatment paradigm for foot care in arthritis patients. These standards and NICE recommendations are included in the latest Royal College of GPs curriculum. They have also informed government policies on commissioning for podiatry services throughout England. Since the inception of the FASTER programme independent reports suggest that access to foot health services for people with rheumatoid arthritis has increased from less than 50% immediately prior to FASTER, to nearly 80% of patients today.
Research at UCL firmly established tacrolimus as the optimal calcineurin inhibitor to use in immunosuppressive regimens following liver transplantation. Compared to ciclosporin its use improved graft survival by 6% and patient survival by 7%. Assuming 550 liver transplants per year in the UK since 2008, we can estimate that, with 90% of patients treated with tacrolimus and 10% ciclosporin, tacrolimus-based immunosuppression has resulted in 165 grafts and 192 lives being saved during the period 2008-13.
Patients with evidence of heart failure following acute myocardial infarction (AMI) have a particularly poor prognosis, with substantially increased risk of death and subsequent cardiovascular events. The Acute Infarct Ramipril Efficacy (AIRE) Randomised Controlled Trial (RCT) was an international trial designed and led by the University of Leeds. AIRE demonstrated, for the first time, that early treatment of patients with clinical evidence of heart failure following AMI with the angiotensin converting enzyme inhibitor (ACEI) ramipril significantly improved survival and quality of life compared with placebo treated patients. The strategy of early initiation of ACEI is now a cornerstone in the management of patients suffering from AMI, leading to a global improvement in post-AMI outcomes.
Congenital disorders are causes of major morbidity and mortality worldwide. Using autozygosity mapping in a local community of Pakistani origin who have high rates of inherited recessive disorders due to consanguineous unions, we have identified more than 30 novel disease genes. Isolating these previously unknown molecular defects has enabled us to develop key diagnostic assays, subsequently provided by clinical laboratories globally. Our work has provided thousands of patients with a definitive diagnosis, removing the need for complex clinical testing. Those affected can be offered focused management and early therapeutic intervention as well as carrier and prenatal testing for themselves and family members. Our findings also provide new research opportunities for previously undefined diseases.