Newborn Screening Today and Tomorrow: A Brief Report from the International Primary Immunodeficiencies Congress.

This article presents the report of the session on "Newborn Screening for Primary Immunodeficiencies-Now What?" organised during the International Primary Immunodeficiency Congress (IPIC) held in November 2023. This clinical conference was organised by the International Patient Organisation for Primary Immunodeficiencies (IPOPI), the global patient organisation advocating for primary immunodeficiencies (PIDs) in patients. The session aimed at exploring the advances in newborn screening (NBS) for severe combined immunodeficiency, starting with the common practice and inserting the discussion into the wider perspective of genomics whilst taking into consideration the ethical aspects of screening as well as incorporating families and the public into the discussions, so as to ensure that NBS for treatable rare disorders continues to be one of the major public health advances of the 20th century.

The PID Odyssey 2030: outlooks, unmet needs, hurdles, and opportunities - proceedings from the IPOPI global multi-stakeholders' summit (June 2022).

IPOPI held its first Global Multi-Stakeholders' Summit on 23-24 June 2022 in Cascais, Portugal. This IPOPI initiative was designed to set the stage for a stimulating forward-thinking meeting and brainstorming discussion among stakeholders on the future priorities of the PID community. All participants were actively engaged in the entire Summit, bringing provocative questions to ensure a high level of discussion and engagement, and partnered in identifying the outlooks, unmet needs, hurdles and opportunities of PIDs for 2030. The topics that were covered include diagnosis (e.g., newborn screening [NBS], genomic sequencing- including ethical aspects on the application of genomics on NBS, the role of more accurate and timely diagnostics in impacting personalized management), treatment (e.g., the therapeutic evolution of immunoglobulins in a global environment, new therapies such as targeted therapies, new approaches in curative therapies), the interactions of Primary ID with Secondary ID, Autoinflammatory Diseases and other diseases as the field experiences an incessant evolution, and also the avenues for research in the field of humanities and human sciences such as Patient-Reported Outcome Measures (PROMs), Patient-Reported Experience Measures (PREMs), and Health-Related Quality Of Life (HRQoL). During this meeting, all participants contributed to the drafting of recommendations based on our common understanding of the future opportunities, challenges, and scenarios. As a collection of materials, perspectives and summaries, they are succinct and impactful and may help determine some of the next key steps for the PID community.

Primary immunodeficiencies (PID) Life Index in Southeast Asia: A comparative analysis of PID Principles of Care (PoC).

Objective: To analyze the implementation of the Principles of Care (PoC) in primary immunodeficiencies (PID) in Southeast Asia (SEA) countries - six years after its call of action. Methodology: Using the newly developed PID Life Index software, the index of implementation of principles of care in the management of PIDs patients involving the six participating SEA countries (Cambodia, Indonesia, Malaysia, Vietnam, Thailand, and Philippines) were extracted. For each of the six separate principles, the index from the six countries will be compared and presented based on the calculated index. Results: Comparative analysis of the six principles of care of PID in the SEA countries showed low diagnostic rate with minimal availability of diagnostic tests options. Generally, almost all SEA countries provide curative treatments, vaccines, and anti-infectious therapies although the reimbursement scheme varied in relieving patients' financial burden. We also highlighted the active involvement of patient organizations in SEA, with main areas of work focused on advocacy and increasing awareness among public and healthcare professionals. Discussion and conclusion: It is applaudable that the SEA continent is gradually strengthening its work in management of PID, especially in Thailand and Vietnam. However, more emphasis must be placed among stakeholders in SEA countries towards successful implementation of the PoC for a holistic management of PID patients.

Towards Achieving Equity and Innovation in Newborn Screening across Europe.

Although individual rare disorders are uncommon, it is estimated that, together, 6000+ known rare diseases affect more than 30 million people in Europe, and present a substantial public health burden. Together with the psychosocial burden on affected families, rare disorders frequently, if untreated, result in a low quality of life, disability and even premature death. Newborn screening (NBS) has the potential to detect a number of rare conditions in asymptomatic children, providing the possibility of early treatment and a significantly improved long-term outcome. Despite these clear benefits, the availability and conduct of NBS programmes varies considerably across Europe and, with the increasing potential of genomic testing, it is likely that these differences may become even more pronounced. To help improve the equity of provision of NBS and ensure that all children can be offered high-quality screening regardless of race, nationality and socio-economic status, a technical meeting, endorsed by the Slovenian Presidency of the Council of the European Union, was held in October 2021. In this article, we present experiences from individual EU countries, stakeholder initiatives and the meeting's final conclusions, which can help countries attempting to establish new NBS programmes or expand existing provision.

The PID Life Index: an interactive tool to measure the status of the PID healthcare environment in any given country.

BACKGROUND: The "Primary Immunodeficiencies (PIDs) principles of care" were published in 2014 as the gold standard for care of patients with PIDs, setting a common goal for stakeholders to ensure that patients with PID have access to appropriate care and good quality of life. Since then, IPOPI (the International Patient Organisation for Primary Immunodeficiencies), has been working with national PID patient organisations as well as collaborating with scientific and medical institutions and experts to bring these principles closer to the day-to-day life of individuals with PIDs. METHOD: The six PID Principles of Care were revised to consider advances in the field, as well as political developments that had occurred after their initial publication in 2014. Based on this revision the list was updated, and a new principle was added. The six established principles were: diagnosis, treatment, universal health coverage, specialised centres, national patient organisations and registries. Each principle was structured and measured through a series of criteria, and was given the same weight, as they have been considered to all be equally important. Specific weights were attributed to the criteria depending on their relevance and importance to quantify the principle. The index was translated into a survey for data collection: initially involving data from selected countries for a pilot, followed by integration of data from IPOPI's national member organisations and key countries. RESULTS: The PID Life Index was developed in 2020 to assess the status of the PID environment and the implementation of the 6 principles worldwide. The Index allows for benchmarking countries either according to a set of principles and criteria or based on the user's preferences. This can be displayed in an interactive map or through a data visualisation system. CONCLUSION: The PID Life Index has been developed successfully and has potential to become an important source of information for PID stakeholders, to increase awareness and information as well as support advocacy initiatives on PIDs nationally, regionally or globally.

The PID Principles of Care: Where Are We Now? A Global Status Report Based on the PID Life Index.

A global gold standard framework for primary immunodeficiency (PID) care, structured around six principles, was published in 2014. To measure the implementation status of these principles IPOPI developed the PID Life Index in 2020, an interactive tool aggregating national PID data. This development was combined with a revision of the principles to consider advances in the field of health and science as well as political developments since 2014. The revision resulted in the following six principles: PID diagnosis, treatments, universal health coverage, specialised centres, national patient organisations and registries for PIDs. A questionnaire corresponding to these principles was sent out to IPOPI's national member organisations and to countries in which IPOPI had medical contacts, and data was gathered from 60 countries. The data demonstrates that, regardless of global scientific progress on PIDs with a growing number of diagnostic tools and better treatment options becoming available, the accessibility and affordability of these remains uneven throughout the world. It is not only visible between regions, but also between countries within the same region. One of the most urgent needs is medical education. In countries without immunologists, patients with PID suffer the risk of remaining undiagnosed or misdiagnosed, resulting in health implications or even death. Many countries also lack the infrastructure needed to carry out more advanced diagnostic tests and perform treatments such as hematopoietic stem cell transplantation or gene therapy. The incapacity to secure appropriate diagnosis and treatments affects the PID environment negatively in these countries. Availability and affordability also remain key issues, as diagnosis and treatments require coverage/reimbursement to ensure that patients with PID can access them in practice, not only in theory. This is still not the case in many countries of the world according to the PID Life Index. Although some countries do perform better than others, to date no country has fully implemented the PID principles of care, confirming the long way ahead to ensure an optimal environment for patients with PID in every country.

Global immunoglobulin supply: steaming towards the iceberg?

PURPOSE OF REVIEW: This review describes how plasma is sourced for fractionation into plasma-derived medicinal products (PDMPs), such as immunoglobulin (Ig) together with differences between plasma from whole blood (recovered plasma) and from plasmapheresis (source plasma) in terms of global plasma supply. Specific areas of growth in immunoglobulin use are identified alongside novel therapies, which may reduce demand for some immunoglobulin indications. RECENT FINDINGS: There has been a 6--8% annual growth in immunoglobulin use. Secondary immunodeficiency alongside improved recognition and diagnosis primary immunodeficiency disorders are drivers whereas the novel neonatal Fc receptor inhibitors (FcRni) may reduce demand for some immunomodulatory indications. SUMMARY: There is a significant geographical imbalance in global supply of plasma with 65% collected in the United States. This results in a dependency of other countries on United States supply and argues for both more plasma supply and greater regionally balanced plasma collection. In addition, progress towards a transparent, regulated and well tolerated framework for the coexistence of unpaid and compensated plasma donations is needed as unpaid donation will not be sufficient. These discussions should be informed by the needs of patients for this life-saving therapy, the care of donors and the safety of plasma and PDMPs.

The Development of a New Questionnaire to Measure the Burden of Immunoglobulin Treatment in Patients with Primary Immunodeficiencies: The IgBoT-35.

PURPOSE: To describe the development and psychometric testing of a new questionnaire to measure the burden of immunoglobulin treatment (Ig) from the perspective of patients with primary immunodeficiencies (PID). PATIENTS AND METHODS: An online, cross-sectional survey was administered to PID patients across 10 countries (nine European and Canada) who were receiving either intravenous (IVIg) or subcutaneous (SCIg) immunoglobulin therapy. The range and distribution of the responses (ie, levels of missing data, floor and ceiling effects), exploratory factor analysis (using factor loadings of 0.4 or greater) and measures of internal consistency reliability (ie, Cronbach's alpha coefficient, inter-item and item-total correlations) were used to identify the domain and item pool. RESULTS: In total, 472 patients completed the questionnaire, of which 395 were included in the analysis (32% underwent IVIg and 67% underwent SCIg). The final instrument contained 34 items across eight domains of treatment burden (time, organisation and planning, leisure and social, interpersonal relationships, employment and education, travel, consequences of treatment and emotional) and an additional Ig treatment burden global question at the end of the measure. All the scales achieved good internal reliability (Cronbach's alpha coefficient ranged from 0.70 to 0.85) and, with the exception of one item exceeded the minimum threshold of 0.35 for item-total correlations. Treatment burden was lower than anticipated across the different treatment routes and countries, although overall was more burdensome for patients undergoing IVIg compared to SCIg treatment. CONCLUSION: The IgBoT-35 appears to be a reliable, patient-generated questionnaire and may help to identify more individualised and preferred therapies for the PID patient when used in clinical practice. A new survey with a sample of US patients is currently being undertaken to further establish its validity and conceptual model. The overall Ig burden of treatment scores appeared to be low. PID patient preferences are important to guide treatment decisions and ensuring patients receive the right treatment at the right time.

Improving current immunoglobulin therapy for patients with primary immunodeficiency: quality of life and views on treatment.

BACKGROUND: Subcutaneous or intravenous immunoglobulin replacement is the mainstay of treatment for most patients with primary immunodeficiency disease (PID). The purpose of this study was to gain an understanding of how existing PID therapies affect patient lives and to identify desired improvements to immunoglobulin treatments. METHODS: An online questionnaire was made available through the International Patient Organisation for Primary Immunodeficiencies to patients with PID and their caregivers regarding current treatment satisfaction, living with PID, and patient preferences using a conjoint approach. Health-related quality of life was canvassed via questionnaires using the Short Form 12 Health Survey and EuroQoL 5 Dimensions. RESULTS: A total of 300 responded to the survey (72% patients with PID and 28% caregivers) from across 21 countries, mostly the UK, Sweden, Canada, France, Germany, and Spain. Fifty-three percent and 45% of patients received intravenous and subcutaneous therapy, respectively. Most respondents (76%) were satisfied with their current treatment, reflecting the benefits that immunoglobulin therapy provides for patient health and well-being. However, patients remained below the physical and mental well-being norms for health-related quality of life as determined by the questionnaire. All respondents expressed a desire for 4-weekly infusions, the ability to administer these at home, self-administration, shorter duration of administration, and fewer needle sticks. CONCLUSION: The results of this survey highlight the importance of providing access to different treatment options and modes of administration to ensure individual patient needs are best met.

Primary immune deficiencies - principles of care.

Primary immune deficiencies (PIDs) are a growing group of over 230 different disorders caused by ineffective, absent or an increasing number of gain of function mutations in immune components, mainly cells and proteins. Once recognized, these rare disorders are treatable and in some cases curable. Otherwise untreated PIDs are often chronic, serious, or even fatal. The diagnosis of PIDs can be difficult due to lack of awareness or facilities for diagnosis, and management of PIDs is complex. This document was prepared by a worldwide multi-disciplinary team of specialists; it aims to set out comprehensive principles of care for PIDs. These include the role of specialized centers, the importance of registries, the need for multinational research, the role of patient organizations, management and treatment options, the requirement for sustained access to all treatments including immunoglobulin therapies and hematopoietic stem cell transplantation, important considerations for developing countries and suggestions for implementation. A range of healthcare policies and services have to be put into place by government agencies and healthcare providers, to ensure that PID patients worldwide have access to appropriate and sustainable medical and support services.