Reference: April 2025 | Issue 4 | Vol 11 | Page 11
International disease registries are longitudinal and structured collectives for the homogenous compiling and analysing of data, usually relating to patients and a particular disease. Data collection focuses on specific patient populations and is designed to evaluate particular outcomes for clinical, socioeconomic, scientific research, or policy purposes. They represent coordinated efforts to collect uniform information across multiple countries and healthcare systems to track disease patterns, treatment outcomes, and patient characteristics over time, and intercountry variations in outcome measures.
Unlike short-term research studies, such as most randomised controlled trials (RCTs), registries provide ongoing, longitudinal real-world data (RWD) that can reveal trends and patterns that might otherwise remain undetected, thus offering significant more understanding of a particular disease.
It’s not just why you collect the data that matters; it’s how. Accuracy, reliability and homogeneity are vital. In the context of asthma management, international registries are particularly valuable because they provide insights into how variable the disease can be and how it manifests across different populations, environments, and healthcare systems.
These registries capture information from routine clinical practice settings rather than the highly controlled environments of clinical trials. Thus these types of registries are much more reflective of real world patient and healthcare experiences.
The International Severe Asthma Registry (ISAR) is the first global network specifically dedicated to collecting standardised data on patients with severe asthma. Launched in 2017, ISAR was created to address the significant knowledge gaps in the understanding and treatment of severe asthma. It brings together existing national registries and newly created registries under a standardised data collection platform.
ISAR operates under a collaborative framework that involves clinicians and researchers across multiple countries, including Ireland. Its governance structure includes a Steering Committee comprising international experts who oversee data collection, research priorities, and dissemination of findings.
The registry now encompasses data from over 30 countries spanning six continents, making it one of the largest sources of real-world evidence in respiratory diseases globally. There are 35,000 patients with severe asthma enrolled in this anonymised international registry. The total number of local or national registries feeding into this is over 330.
One of the primary strengths of the ISAR is its extensive global scope and scale, encompassing data from a diverse array of healthcare settings across multiple countries, and the experience of the healthcare clinicians and researchers involved. This broad geographic coverage allows for insightful analyses of variations in disease patterns, differing treatment approaches and their outcomes comparatively, and also that these are real world patient outcomes – worldwide.
Despite the inherent challenges of integrating data from countries with distinct healthcare systems, ISAR maintains robust data quality by utilising standardised definitions (such as those from GINA), and standardised variables and collection methodologies. This meticulous standardisation is crucial, enabling meaningful cross-country comparisons and enhancing the reliability of insights derived from the registry data.
Moreover, ISAR’s collaborative research framework significantly contributes to its effectiveness. By uniting academic researchers, clinical experts, and industry stakeholders, the registry fosters extensive knowledge sharing and effectively leverages diverse expertise, particularly in study design and data interpretation.
The registry gathers comprehensive data, including detailed patient demographics, comorbid conditions, lung function parameters, biomarkers such as blood eosinophils (BEC) and fraction of exhaled nitric oxide (FeNO), treatment patterns, and clinical outcomes, thus providing a holistic and nuanced understanding of severe asthma management.
Recognising the rapidly evolving nature of asthma care, ISAR continuously updates its data collection protocols to integrate innovative therapies such as novel biological agents, and new outcome measures, thereby ensuring ongoing relevance and applicability in advancing asthma management practices globally.
Real-world data from registries such as ISAR offer critical insights that significantly complement and indeed expand upon evidence from RCTs. Clinical trials typically have stringent inclusion and exclusion criteria, excluding patients with comorbidities, extreme ages, or complex presentations.
Conversely, ISAR captures a more representative and diverse patient population reflective of real-world clinical practice. Indeed within ISAR many patients that would have been excluded from the assessment of advanced biologic monoclonal antibody trials in severe asthma RCTs, for various reasons, are on biological therapies and their response and disease trajectories are being mapped. This adds significantly to our knowledge.
Additionally, while RCTs primarily assess treatment efficacy under controlled, ideal conditions, registries like ISAR measure treatment effectiveness within routine clinical environments, accounting for practical considerations such as medication adherence, patient preferences, and healthcare system limitations. ISAR has notably contributed to understanding how biologic therapies for severe asthma perform in everyday clinical settings, beyond the controlled scenarios of clinical trials.
ISAR is now in its eighth year. This allows for comprehensive evaluations of long-term treatment effects, safety profiles, disease progression, and the natural history of severe asthma.
ISAR captures extensive information on healthcare resource utilisation, including emergency department visits, hospitalisations, and medication usage patterns including cumulative exposure to oral corticosteroid (OSC). This allows comparison of various healthcare systems, providing crucial insights for health economic analyses and highlighting the global burden of severe asthma.
Since its inception, ISAR has generated important insights into severe asthma that inform clinical practice and policy. Because ISAR aggregates a large, diverse patient population, it has shed light on the characteristics and burden of severe asthma on a worldwide scale. For example, ISAR data confirmed that severe asthma patients often remain poorly controlled despite maximal therapy. In one analysis, less than 25 per cent achieved well-controlled disease, even on high-intensity treatment.
ISAR has also highlighted the high comorbidity burden and OCS burden in patients with severe asthma, reinforcing how severe asthma contributes to disproportionate healthcare utilisation and costs.
Another key finding has been the variation in outcomes across countries.
A 2024 ISAR study found striking between-country differences in severe asthma exacerbation rates: Patients with similar profiles had annual severe exacerbation rates ranging from about 0.04 in Argentina to 0.88 in Saudi Arabia, even after adjusting for patient factors. This suggests that unexplained environmental or healthcare system factors influence asthma outcomes, underscoring the need to tailor management guidelines to local contexts.
ISAR has provided real-world evidence on the effectiveness of advanced therapies as well. For instance, analyses of biologic therapy in ISAR revealed that while most patients continue on their initial biologic, a subset (~11 per cent) switch to a different biologic due to inadequate efficacy or side effects.
The most common switch observed was from anti-IgE (omalizumab) to anti–IL-5/5R agent (mepolizumab/reslizumab/benralizumab). Through biomarker signalling, patients who needed to stop or switch biologics tended to have more severe disease (higher eosinophils and more frequent exacerbations) at baseline. These findings emphasise the importance of phenotyping patients to select the right therapy and the potential value of structured switching criteria in practice.
Collectively, the evidence from ISAR – spanning disease burden, risk factors, treatment responses, and healthcare gaps – is informing more effective and personalised approaches to severe asthma management worldwide.
Research using ISAR’s extensive dataset has led to numerous publications in high-impact journals. Over 28 peer-reviewed papers (and dozens of conference abstracts) have been published from ISAR data that have brought together research clinicians from around the globe. In practice, this means hundreds of respiratory specialists and care teams worldwide are inputting patient information under standardised protocols. This allows for a global understanding of best practices.
Importantly, each national or regional registry retains ownership of its data but shares it with ISAR for approved research, ensuring local engagement and data quality. Individual registries can utilise ISAR data against a research hypothesis or question.
Currently, the focus of the ISAR community is on assessing the impact of earlier access to biologics and whether this can alter positively the natural course of patients developing severe asthma and airway remodeling that can cause irreversible lung obstruction. Another current goal is assessing the long-term outcomes in patients with severe asthma achieving remission.
In summary, international disease registries, like the ISAR, systematically collect standardised longitudinal real world data on specific patient populations to inform clinical practice, research, policy, and healthcare economics.
Established in 2017, ISAR addresses knowledge gaps in severe asthma by aggregating data from over 35,000 patients across 30 countries, supported by more than 330 regional registries. Its strength lies in comprehensive data collection, including demographics, biomarkers, treatment patterns, outcomes, and healthcare utilisation, which accurately reflects real-world clinical settings, differing from controlled environments typical of RCTs for example. This enables ISAR to capture treatment effectiveness, long-term disease progression, safety profiles, and patient adherence beyond short-term trials.
Insights derived from ISAR have significantly advanced understanding of severe asthma, revealing persistent disease control issues despite intensive treatments, the considerable burden of oral corticosteroid use, and striking international variations in exacerbation rates. ISAR data have also elucidated patterns in biologic therapy effectiveness, switching biologics and asthma remission, emphasising patient phenotyping and structured therapy-switching criteria.
Through collaborative global research leading to numerous influential publications, ISAR informs personalised management strategies and healthcare policies worldwide, ultimately aiming to improve patient outcomes and healthcare resource allocation in severe asthma.
