The future of cystic fibrosis care: a global perspective

Abstract

EXECUTIVE SUMMARY The past six decades have seen remarkable improvements in health outcomes for people with cystic fibrosis (CF), which was once a fatal disease of infants and young children. However, although life expectancy for people with CF has increased substantially, the disease continues to limit survival and quality of life, and results in a significant burden of care for people with CF and their families. Moreover, recent epidemiological studies in the past two decades have shown that CF occurs and is more frequent than was previously thought in non-European populations and in regions of the world where it had not previously been described. The Lancet Respiratory Medicine Commission was formed to assess the global health and economic costs of CF care over the next three decades and to identify opportunities for progress in the care of people with CF. challenges that need to be addressed, and to serve as a blueprint for the future of CF care. This Commission was established at a time of immense change in CF clinical care including enhanced survival, widespread genetic testing supporting the diagnosis of CF in regions of the world where it was previously thought to be or non-existent and the advent of a growing number of CFTR-directed therapies which are likely to further alter the natural trajectory of the disease. This document is intended to bring to the attention of patients, health-care professionals, researchers, funders, service providers, policy makers the variety of challenges associated with this changing landscape and to serve as a blueprint for the future of CF care. what was previously a universally fatal disease of children. In considering the future of CF care, the Commission focused on five key areas, which are discussed in this report: the changing epidemiology of CF (section 1); future challenges of clinical care and its delivery (section 2); the building of CF care globally (section 3); novel therapeutics (section 4); and patient engagement (section 5) (summarized in panel 1). Since the discovery of the cystic fibrosis transmembrane regulator (CFTR) gene in the late 1980’s, triggered a surge of basic research which has enhanced understanding of the pathophysiology and the genotype/phenotype relationships of this clinically variable disease. Until recently, available treatments could be used to control symptoms and limit the complications of CF, but advances in CFTR modulator therapies to address the basic defect of CF have been phenomenal and the field is evolving rapidly. Advances in clinical care have been multifaceted and include earlier diagnosis through the implementation of newborn screening programmes, formalised airway clearance therapy, and reduced malnutrition through the use of effective pancreatic enzyme replacement and a high-energy, high protein diet. Centre-based care has become the norm in high-income countries, allowing patients to benefit from the skills of expert members of multi-disciplinary teams. Pharmacological interventions to address pulmonary manifestations now include agents that target airway mucus and airway surface liquid hydration, as well as antimicrobial therapy, including antibiotic eradication treatment in early infection and protocols for maintenance therapy in chronic infection. The challenges faced by all stakeholders in building and developing CF care globally are substantial, but many opportunities exist for improved care and better health outcomes for patients. Here, we discuss changes in diagnostic approaches including advances in genetic testing, advances in newborn screening and how it is changing landscape of the CF population, The occurrence and impact of CF in non-European populations and on different continents is explored as is. We highlight the current and future opportunities as well are the challenges for clinical care in both countries with established CF care programs and what care might look like for low- and middle-income countries where care programs more fragmented and less well funded. to the availability of integrated multi-disciplinary care and new disease-modifying treatments. The recent advances in CFTR modulator therapies to address the basic defect of CF have been phenomenal and current knowledge and future directions are appraised. The cost of new therapies is currently high and there are concerns about the affordability of those medications currently available and those under development especially when considered from a global perspective. As median age of CF has increased, there has been an associated rapid rise in the adult population, we evaluate opportunities for the use of new technologies to support engagement between patients and healthcare providers in novel ways to positively impact on the burden of care and support patient choice and yet to optimise healthcare outcomes. Challenges and opportunities in these key areas are being discussed to provide a conceptional framework for future CF care throughout the world. Panel 1 Key Messages of the Lancet Commission for Cystic Fibrosis Section 1 The changing epidemiology of cystic fibrosis Newborn screening testing has been implemented in many parts of the world supporting an early diagnosis of CF. Improved molecular genetic diagnostics have allowed the identification of CF in non-European populations and in individuals with nonclassical presentations of CF and related disorders. CFTR related disease represents a spectrum ranging from single organ manifestations to a multi-system disease. Defining the threshold of CFTR function associated with disease manifestations is a priority to guide monitoring and treatment decisions. Section 2 Clinical care and its delivery Children with CF are healthier and the vast majority are living well into adulthood. Diagnostics to allow earlier diagnosis of disease manifestations, deterioration of organ function and new airway infections are key priorities. Models of care need to consider management approaches (including disease monitoring) to maintain health and delay lung transplantation and yet limit the burden of care. Section 3 Cystic fibrosis care in developing nations Information about genetic and clinical features CF in non-European populations have improved understanding of the disease in low- and middle-income countries. Access to CF therapies which is sustained and affordable for people with CF living in LMIC is needed which requires partnerships between lay organisations, governments and the pharmaceutical industry. Clinical registries in countries where CF is now recognised are developing and there is a need to harmonise data elements including established CF registries to support understanding of health care outcomes especially in LMIC. Section 4 Novel therapeutics CFTR modulator therapy targeting the basic molecular defect have been developed for specific CFTR mutations and is associated with improved health outcomes including better pulmonary function and nutritional status and enhanced quality of life. New CFTR modulator drugs are showing promise in CFTR mutation where earlier modulators were ineffective. Early commencement of CFTR-directed therapies may prevent the establishment of irreversible airways complications and slow progression disease in older patients. Drug development requires substantial investment and contributes to the current high-cost of approved CFTR modulators. This has in turn contributed to delays in funding for such therapies in many countries and current drug prices make them unaffordable for many LMICs. Section 5 Patient experience, engagement and involvement Complexity of care has increased for people with CF in parallel with increased life expectancy leading to significant burden of care and disease monitoring. Novel technologies have the potential to support self-monitoring and shared decision making between patient and health care team. Mental health complications are more common in people with CF (including parents of children with CF) than the general community, impacting on quality of life. Adherence to complex therapeutic regimens is often sub-optimal and impacts of clinical outcomes. Patients are highly engaged in the approaches to delivery of clinical care and their perspective of the important research priorities. CF patient organisations provide important roles in patient advocacy to delivery of clinical care, treatment access, and support and education for patients with CF and their families.