Best Practice & Research Clinical Rheumatology 28 (2014) 173e174
Contents lists available at ScienceDirect
Best Practice & Research Clinical Rheumatology journal homepage: www.elsevierhealth.com/berh
Preface The paediatric rheumatic diseases comprise a vast array of disorders that range from single gene diseases, multifactorial inflammatory diseases, to non-inflammatory pain syndromes. Research has led to an increased understanding of the pathogenesis and outcomes of these disorders. It is therefore imperative that we develop the ability to apply the new knowledge that has been generated over the last few years to improve the quality of lives of our patients and their families. Scientific societies to set the educational and research agenda have been established in North America and Europe since the 1990s and subsequently involved all the other continents. Global clinical trial networks have also been established. This volume in Best Practice Research Clinical Rheumatology consists of reviews from experts on the progress in research from the delineation of clinical syndromes to translation of research into new therapies. Advances in basic science and translational research have resulted in major clinical impacts over the last decade. The application of molecular genetics and gene expression data to clinical medicine, which started with cancer research, is now becoming applicable in diseases with multiple genetic and environmental influences (known as complex genetic traits), such as all inflammatory rheumatologic illnesses. Within paediatric rheumatology, the last decade saw the detection of genetic mutations in multisystem diseases (see Ombrello and Gattorno chapters), which offer novel therapeutic targets, and for the first time such patients can be “cured” with biologic therapy (although therapy must be maintained). Genomics is beginning to impact on therapeutics in order to achieve better results by the possibility to stratify patients according to genotypes and phenotypes: stratified medicine. Another term, “precision medicine”, refers to the use of molecular biology to identify the most appropriate therapeutic target, and the use of drug(s) to the target. This is discussed by Vastert and Prakken. The ultimate goal of current research would be precision medicine that can be given for a short time, rather like an antibiotic, and so the potential side effects of long-term use will not be a significant problem. One of the key advances has been the definition of disease activity and outcomes so that clinical trials could proceed with consistent outcome measures and therefore allow comparisons between trials. Luca and Feldman have provided an excellent summary of what has been achieved to date. There has been major therapeutic advances especially in the last decade with the criteria of efficacy of a drug being pushed from the initial 30% improvement to 70e90% and the aim of all clinicians is to achieve remission. To this end, preliminary criteria for clinical remission for JIA have been defined and are undergoing further validation. . Kessler and Becker have reviewed the current field of therapeutics in juvenile arthritis. As some of the initial trials were done prior to the now universally recognized JIA classification, the terms juvenile rheumatoid arthritis, juvenile chronic arthritis (old terms) and JIA all appear in the text, and reflect the populations that were studied at the time. The therapeutic advances particularly over the past decade have resulted in marked reduction of disease activity in many more patients, but as the authors have concluded, there is still a great deal to be learned about the safest and most effective therapies for individual patients. New drug development should aim for clinical remission of disease.
http://dx.doi.org/10.1016/j.berh.2014.06.001 1521-6942/© 2014 Elsevier Ltd. All rights reserved.
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Preface / Best Practice & Research Clinical Rheumatology 28 (2014) 173e174
It has also become abundantly clear that the placebo controlled trial design is not particularly useful when the patient population is heterogeneous, and as we move into the era of stratified medicine and precision medicine (see definition above), this design is becoming redundant. It is also difficult for trials in rare diseases, even in the case of mongenic diseases. A discussion of what is on the horizon is provided in this volume by Smith, Williamson and Beresford. Paediatric rheumatologists have long recognized groups of inflammatory disorders that defied both diagnosis and classification. The term “autoinflammation” defines disorders with spontaneous attacks of inflammation that are primarily based on disorders of the innate immune system, most of which thus far appear to be a result of single-gene mutations. An approach to diagnose this fascinating group of disorders is provided by Federici and Gattorno. Another group of inflammatory diseases is characterized by granulomatous inflammation. There is a large overlap in this group of patients with immune deficiency states, either overt or subtle. Rose and Wouters have provided a comprehensive review of this group of diseases. Macrophage activation syndrome, a disorder with significant overlap with primary hemophagocytic lymphohistiocytosis, has been increasing recognized to complicate several paediatric rheumatic diseases, especially systemic-JIA, systemic lupus erythematosus and Kawasaki disease. This topic is reviewed extensively by Alexei Grom. Pain is a prevalent clinical problem whether the pain has an inflammatory or non-inflammatory origin. Many patients in paediatric rheumatology clinics consist of young people with pain syndromes. Therefore it is vital that better understanding of the aetiology of pain, the perception of pain and its clinical management is obtained. Research in paediatric and neonatal pain is beginning to yield interesting observations in neuroanatomy and neurophysiology, as summarized in the chapter by Sue Ellen Walker. A very useful clinical guide for the assessment and treatment of pain in children and adolescents is provided by Lalloo and Stinson. As this volume of Best Practice Research Clinical Rheumatology demonstrates, the field of paediatric rheumatology has made great advances over the last few years, yet there is still a long way to go. The outstanding chapters in this volume provide a research agenda which, if followed, should lead to even better understanding of the aetiology of paediatric rheumatic diseases, and how to monitor and treat them. Patricia Woo* Paediatric Rheumatology, 3rd floor, Rayne Building, UCL, 5, University Street, London WC1E 6JF, UK Ronald M. Laxer Paediatrics and Medicine, The Hospital for Sick Children, University of Toronto, Canada Corresponding author. Tel.: þ44 (0)207 679 6364; fax: þ44 (0)207 679 6212. E-mail address: [email protected]
Contents lists available at ScienceDirect
Best Practice & Research Clinical Rheumatology journal homepage: www.elsevierhealth.com/berh
Preface The paediatric rheumatic diseases comprise a vast array of disorders that range from single gene diseases, multifactorial inflammatory diseases, to non-inflammatory pain syndromes. Research has led to an increased understanding of the pathogenesis and outcomes of these disorders. It is therefore imperative that we develop the ability to apply the new knowledge that has been generated over the last few years to improve the quality of lives of our patients and their families. Scientific societies to set the educational and research agenda have been established in North America and Europe since the 1990s and subsequently involved all the other continents. Global clinical trial networks have also been established. This volume in Best Practice Research Clinical Rheumatology consists of reviews from experts on the progress in research from the delineation of clinical syndromes to translation of research into new therapies. Advances in basic science and translational research have resulted in major clinical impacts over the last decade. The application of molecular genetics and gene expression data to clinical medicine, which started with cancer research, is now becoming applicable in diseases with multiple genetic and environmental influences (known as complex genetic traits), such as all inflammatory rheumatologic illnesses. Within paediatric rheumatology, the last decade saw the detection of genetic mutations in multisystem diseases (see Ombrello and Gattorno chapters), which offer novel therapeutic targets, and for the first time such patients can be “cured” with biologic therapy (although therapy must be maintained). Genomics is beginning to impact on therapeutics in order to achieve better results by the possibility to stratify patients according to genotypes and phenotypes: stratified medicine. Another term, “precision medicine”, refers to the use of molecular biology to identify the most appropriate therapeutic target, and the use of drug(s) to the target. This is discussed by Vastert and Prakken. The ultimate goal of current research would be precision medicine that can be given for a short time, rather like an antibiotic, and so the potential side effects of long-term use will not be a significant problem. One of the key advances has been the definition of disease activity and outcomes so that clinical trials could proceed with consistent outcome measures and therefore allow comparisons between trials. Luca and Feldman have provided an excellent summary of what has been achieved to date. There has been major therapeutic advances especially in the last decade with the criteria of efficacy of a drug being pushed from the initial 30% improvement to 70e90% and the aim of all clinicians is to achieve remission. To this end, preliminary criteria for clinical remission for JIA have been defined and are undergoing further validation. . Kessler and Becker have reviewed the current field of therapeutics in juvenile arthritis. As some of the initial trials were done prior to the now universally recognized JIA classification, the terms juvenile rheumatoid arthritis, juvenile chronic arthritis (old terms) and JIA all appear in the text, and reflect the populations that were studied at the time. The therapeutic advances particularly over the past decade have resulted in marked reduction of disease activity in many more patients, but as the authors have concluded, there is still a great deal to be learned about the safest and most effective therapies for individual patients. New drug development should aim for clinical remission of disease.
http://dx.doi.org/10.1016/j.berh.2014.06.001 1521-6942/© 2014 Elsevier Ltd. All rights reserved.
174
Preface / Best Practice & Research Clinical Rheumatology 28 (2014) 173e174
It has also become abundantly clear that the placebo controlled trial design is not particularly useful when the patient population is heterogeneous, and as we move into the era of stratified medicine and precision medicine (see definition above), this design is becoming redundant. It is also difficult for trials in rare diseases, even in the case of mongenic diseases. A discussion of what is on the horizon is provided in this volume by Smith, Williamson and Beresford. Paediatric rheumatologists have long recognized groups of inflammatory disorders that defied both diagnosis and classification. The term “autoinflammation” defines disorders with spontaneous attacks of inflammation that are primarily based on disorders of the innate immune system, most of which thus far appear to be a result of single-gene mutations. An approach to diagnose this fascinating group of disorders is provided by Federici and Gattorno. Another group of inflammatory diseases is characterized by granulomatous inflammation. There is a large overlap in this group of patients with immune deficiency states, either overt or subtle. Rose and Wouters have provided a comprehensive review of this group of diseases. Macrophage activation syndrome, a disorder with significant overlap with primary hemophagocytic lymphohistiocytosis, has been increasing recognized to complicate several paediatric rheumatic diseases, especially systemic-JIA, systemic lupus erythematosus and Kawasaki disease. This topic is reviewed extensively by Alexei Grom. Pain is a prevalent clinical problem whether the pain has an inflammatory or non-inflammatory origin. Many patients in paediatric rheumatology clinics consist of young people with pain syndromes. Therefore it is vital that better understanding of the aetiology of pain, the perception of pain and its clinical management is obtained. Research in paediatric and neonatal pain is beginning to yield interesting observations in neuroanatomy and neurophysiology, as summarized in the chapter by Sue Ellen Walker. A very useful clinical guide for the assessment and treatment of pain in children and adolescents is provided by Lalloo and Stinson. As this volume of Best Practice Research Clinical Rheumatology demonstrates, the field of paediatric rheumatology has made great advances over the last few years, yet there is still a long way to go. The outstanding chapters in this volume provide a research agenda which, if followed, should lead to even better understanding of the aetiology of paediatric rheumatic diseases, and how to monitor and treat them. Patricia Woo* Paediatric Rheumatology, 3rd floor, Rayne Building, UCL, 5, University Street, London WC1E 6JF, UK Ronald M. Laxer Paediatrics and Medicine, The Hospital for Sick Children, University of Toronto, Canada Corresponding author. Tel.: þ44 (0)207 679 6364; fax: þ44 (0)207 679 6212. E-mail address: [email protected]
