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Surging forwards with cystic fibrosis care
Editorial
When cystic fibrosis was first identified in 1938, babies were not expected to survive beyond their first year of life. Today, those born with cystic fibrosis in the USA and UK are expected to live well beyond 40 years as a result of health-care developments seen in the past decade. This progress has created much expectation that current research approaches will deliver even more remarkable improvements in patient outcome in the next few years. It is with great enthusiasm, then, that The Lancet Respiratory Medicine presents this month’s cystic fibrosis-themed issue. The approach towards the treatment of cystic fibrosis has been revolutionised by the discovery nearly 15 years ago that cystic fibrosis is caused by mutations in the CFTR gene. The confluence of genetic research and modern drug design has shifted the focus of pharmaceutical interventions to target this inherited cause of disease, rather than to merely manage symptoms or slow disease progress. In 2011, Bonnie Ramsey and colleagues published the first study to show that correction of the channel defect resulting from a CFTR mutation was possible, using a drug called VX-770 (ivacaftor). Patients with the specific Gly551Asp CFTR mutation who were given ivacaftor had improved predicted FEV1, reduced incidence of pulmonary exacerbations, and increased mean weight gain compared with those given placebo. However, only 4% of patients have the Gly551Asp mutation. Other CFTR mutations are now being targeted by new experimental drugs, such as VC-661 and lumacaftor, in clinical trials. In this issue, Michael Boyle and Kris De Boeck summarise in a Review the state of research and potential treatments for each of the six CFTR mutation groups, and the authors highlight future drug candidates for patients according to their genotype. However, despite the anticipation surrounding these new therapies, many challenges remain. Ivacaftor was approved last year for the treatment of Gly551Asp patients older than 6 years in Europe and the USA. But how can we ensure the timely, fair, and affordable rollout of such expensive personalised medicine? Before individually-tailored treatment can be considered, a patient must be genotyped. This is not yet universal practice. Furthermore, ivacaftor costs about £182 000 or US$294 000 per patient, per year in the UK and www.thelancet.com/respiratory Vol 1 April 2013
USA, respectively, and Boyle and De Boeck predict that the optimum clinical benefit might be achieved only through complicated combinations of various CFTRmodulators. Such multiple-drug therapy will further drive up costs, leading to the thorny question of how we balance the resources society is willing to provide to any individual group of patients. Another long-standing but increasingly worrisome challenge for patients and practitioners is that of infection control, as highlighted in a recent article in The Lancet. Using whole genome sequencing, Josephine Bryant and colleagues reported the first convincing evidence of person-to-person transmission of the nontuberculosis mycobacteria, Mycobacterium abscessus, in adults with cystic fibrosis. Until now, the strictest infection control measures have been focused on those patients with Burkholderia cepacia complex, meticillinresistant Staphylococcus aureus, haemophilus influenza, and multi-resistant Pseudomonas aeruginosa infections. Yet M abscessus infections have increased significantly in the past 10 years, with 3–10% of all US patients with cystic fibrosis now being infected. The disquieting proof that person-to-person transmission of these bacteria is possible demands urgent revision of current, outdated infection-control guidelines. Despite recent breakthroughs in treatment propelling patients with cystic fibrosis to a brighter prognosis in the USA and western Europe, the most elementary obstacles persist in screening for the disease. Neonatal screening methods vary substantially between countries, and remains only partially in practice in Latin America and eastern Europe. As Hartmut Grasemann and Felix Ratjen discuss in a Review in this issue, early diagnosis of the disease, and monitoring of lung damage, is vital for future patient outcomes. Timely interventions can delay disease development, offering a further focus for progress to be made in the fight against cystic fibrosis. As data emerge from the first interventional trials in infants and young children with cystic fibrosis, The Lancet Respiratory Medicine presents itself as an ally to the clinical research community as they determine whether therapies aimed at the very youngest of patients can postpone, or even prevent, the onset of cystic fibrosis lung disease. ■ The Lancet Respiratory Medicine
David Mack www.animatedhealthcare.com
Surging forwards with cystic fibrosis care
See Spotlight page 108 See Review pages 148 and 158 See Articles Lancet 2013; published online March 29. http://www.dx.doi.org/10.1016/ S0140-6736(13)60632-7
91
When cystic fibrosis was first identified in 1938, babies were not expected to survive beyond their first year of life. Today, those born with cystic fibrosis in the USA and UK are expected to live well beyond 40 years as a result of health-care developments seen in the past decade. This progress has created much expectation that current research approaches will deliver even more remarkable improvements in patient outcome in the next few years. It is with great enthusiasm, then, that The Lancet Respiratory Medicine presents this month’s cystic fibrosis-themed issue. The approach towards the treatment of cystic fibrosis has been revolutionised by the discovery nearly 15 years ago that cystic fibrosis is caused by mutations in the CFTR gene. The confluence of genetic research and modern drug design has shifted the focus of pharmaceutical interventions to target this inherited cause of disease, rather than to merely manage symptoms or slow disease progress. In 2011, Bonnie Ramsey and colleagues published the first study to show that correction of the channel defect resulting from a CFTR mutation was possible, using a drug called VX-770 (ivacaftor). Patients with the specific Gly551Asp CFTR mutation who were given ivacaftor had improved predicted FEV1, reduced incidence of pulmonary exacerbations, and increased mean weight gain compared with those given placebo. However, only 4% of patients have the Gly551Asp mutation. Other CFTR mutations are now being targeted by new experimental drugs, such as VC-661 and lumacaftor, in clinical trials. In this issue, Michael Boyle and Kris De Boeck summarise in a Review the state of research and potential treatments for each of the six CFTR mutation groups, and the authors highlight future drug candidates for patients according to their genotype. However, despite the anticipation surrounding these new therapies, many challenges remain. Ivacaftor was approved last year for the treatment of Gly551Asp patients older than 6 years in Europe and the USA. But how can we ensure the timely, fair, and affordable rollout of such expensive personalised medicine? Before individually-tailored treatment can be considered, a patient must be genotyped. This is not yet universal practice. Furthermore, ivacaftor costs about £182 000 or US$294 000 per patient, per year in the UK and www.thelancet.com/respiratory Vol 1 April 2013
USA, respectively, and Boyle and De Boeck predict that the optimum clinical benefit might be achieved only through complicated combinations of various CFTRmodulators. Such multiple-drug therapy will further drive up costs, leading to the thorny question of how we balance the resources society is willing to provide to any individual group of patients. Another long-standing but increasingly worrisome challenge for patients and practitioners is that of infection control, as highlighted in a recent article in The Lancet. Using whole genome sequencing, Josephine Bryant and colleagues reported the first convincing evidence of person-to-person transmission of the nontuberculosis mycobacteria, Mycobacterium abscessus, in adults with cystic fibrosis. Until now, the strictest infection control measures have been focused on those patients with Burkholderia cepacia complex, meticillinresistant Staphylococcus aureus, haemophilus influenza, and multi-resistant Pseudomonas aeruginosa infections. Yet M abscessus infections have increased significantly in the past 10 years, with 3–10% of all US patients with cystic fibrosis now being infected. The disquieting proof that person-to-person transmission of these bacteria is possible demands urgent revision of current, outdated infection-control guidelines. Despite recent breakthroughs in treatment propelling patients with cystic fibrosis to a brighter prognosis in the USA and western Europe, the most elementary obstacles persist in screening for the disease. Neonatal screening methods vary substantially between countries, and remains only partially in practice in Latin America and eastern Europe. As Hartmut Grasemann and Felix Ratjen discuss in a Review in this issue, early diagnosis of the disease, and monitoring of lung damage, is vital for future patient outcomes. Timely interventions can delay disease development, offering a further focus for progress to be made in the fight against cystic fibrosis. As data emerge from the first interventional trials in infants and young children with cystic fibrosis, The Lancet Respiratory Medicine presents itself as an ally to the clinical research community as they determine whether therapies aimed at the very youngest of patients can postpone, or even prevent, the onset of cystic fibrosis lung disease. ■ The Lancet Respiratory Medicine
David Mack www.animatedhealthcare.com
Surging forwards with cystic fibrosis care
See Spotlight page 108 See Review pages 148 and 158 See Articles Lancet 2013; published online March 29. http://www.dx.doi.org/10.1016/ S0140-6736(13)60632-7
91