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Systemic sclerosis (SSc) is an important, but uncommon, connective tissue disease with high mortality and has a major non-lethal morbidity. Research at UCL has been instrumental in defining modern management of SSc and has contributed in three main ways. First we have defined the importance of regular proactive screening of cases, secondly we have defined the use of immunosuppression and thirdly we have delineated important clinical and laboratory subsets of SSc that underpin an individualised (or personalised) approach to assessment and treatment. These topics exemplify stepwise progress in management of SSc that also has direct relevance to other more common medical conditions.
Research at UCL into the use of tocilizumab has led to a new treatment and improved care for patients with juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA) in adults. The drug is now approved around the world and recommended by NICE guidelines and is the standard of care in children with systemic onset JIA. It has been prescribed in every rheumatology centre in the UK for patients with severe RA. The impact of the drug on patients is to prevent disability, halt joint damage, improve function and increase quality of life.
An estimated 1% of UK adults suffer from rheumatoid arthritis and the long-term pain and disability associated with it, Historically, however, treatments focused on relieving symptoms and did not control the arthritis itself or prevent disability. An extensive series of clinical trials and associated research programmes at King's College London (KCL) over 20 years has now significantly improved treatment recommendations and thus quality of life for thousands of rheumatoid arthritis patients in the UK, Europe and other countries. Multicentre trials of intensive treatments using conventional drugs have extended the range of drugs available, established the effectiveness of early intensive treatment, and shown that early combination therapies are safe.
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.
Research conducted by Professor TM Cox has led to several advances in the management of lysosomal storage disorders; i) development of miglustat (Zavesca®); now available throughout the world (EMA and FDA approved) for adult patients with Gaucher's disease and throughout the European Union and five other countries worldwide for adult and pediatric patients with Niemann- Pick type C disease, ii) development of the potential successor eliglustat; now in Phase 3 clinical trials, iii) identification of a biomarker for Gaucher's: CCL18/PARC, now incorporated into NHS standard operating procedures for monitoring therapeutic intervention. His pre-clinical research into gene therapy for Tay-Sachs disease also helped establish the NIH-funded Gene Therapy Consortium and gain the FDA's pre-IND approval for clinical trials in 2013, which together have raised public awareness of this disease.
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.
Impact: Health and welfare; a clinical trial demonstrated that statin therapy is ineffective in aortic stenosis; this informed international guidelines and changed clinical practice.
Significance: Unnecessary statin therapy is avoided in up to 500,000 people in the UK alone, saving the NHS £169M p.a. Known statin side-effects of myalgia or hepatic dysfunction are avoided in 30,000 patients.
Beneficiaries: Patients with aortic stenosis; the NHS and healthcare delivery organisations, the economy.
Attribution: Newby and Boon, UoE, undertook the first investigator-led randomised controlled trial of statin therapy in aortic stenosis: the SALTIRE trial.
Reach: Aortic stenosis affects 2% of people over 65. The SALTIRE trial results informed European and N American guidelines and have impacted the treatment of millions of people globally.
Psoriatic arthritis (PsA) is a chronic inflammatory disease of joints, skin and tendons that affects 0.5-0.8% of the population worldwide. PsA can cause substantial psychological and social problems and also causes increased risk of death from cardiovascular disease. Research conducted by Prof Iain McInnes at the University of Glasgow in partnership with leading pharmaceutical company, Janssen, has provided robust evidence of the clinical benefits and safety of the cytokine blocker ustekinumab, leading to its approval for use for PsA by the European Medicines Agency in July 2013. This was the first approval of a PsA drug with a new mode of action in a decade, providing a novel treatment for approximately 1.25 million PsA patients across Europe.
COPD affects up to 3.5 million people in the UK and costs the NHS £700m pa. Over the last 15 years, research by Professor Calverley and colleagues at the University of Liverpool (UoL) has impacted significantly on the care of COPD patients. Specifically, this group showed that routine testing of COPD patients for the presence of bronchodilator reversibility was unreliable and did not predict clinical outcomes. This changed international guideline recommendations in 2007 and the Quality Outcomes Framework payments to GPs in 2009. They showed that oral corticosteroids accelerated recovery from exacerbations and that anti-inflammatory drugs, whether inhaled corticosteroids or PDEIV inhibitors, reduced exacerbations by 25% with a subsequent fall in the number and length of hospitalisations. This led to changed NICE guidance for corticosteroids in 2010 and drug registration with EMA and FDA for the PDEIV inhibitor treatment in 2011. Treatment in UK and Western Europe has changed as a result of this research.
Jayne's team have co-ordinated a sequence of randomised clinical trials, that have defined the standard of care for ANCA vasculitis treatment and shaped national and international guideline statements, NHS national commissioning guidance and an on-going NICE assessment. Together with Ken Smith his group have pioneered the use of the B cell-depleting agent rituximab, in vasculitis, contributing key evidence that led to its licence approval (USA and EU) for this indication. Ken Smith's group supported by Jayne's clinical team have discovered novel therapeutic biomarkers, patented and being assessed in Phase II clinical studies, that promise to deliver "personalised medicine" in this and related conditions. These activities have harmonised the management of vasculitis, are improving patient outcomes, and have provided a resource for on-going scientific and clinical studies.