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.

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.

Rapid Low-Cost Microarray-Based Genotyping for Genetic Screening in Primary Immunodeficiency.

Background: Genetic tests for primary immunodeficiency disorders (PIDs) are expensive, time-consuming, and not easily accessible in developing countries. Therefore, we studied the feasibility of a customized single nucleotide variant (SNV) microarray that we developed to detect disease-causing variants and copy number variation (CNV) in patients with PIDs for only 40 Euros. Methods: Probes were custom-designed to genotype 9,415 variants of 277 PID-related genes, and were added to the genome-wide Illumina Global Screening Array (GSA). Data analysis of GSA was performed using Illumina GenomeStudio 2.0, Biodiscovery Nexus 10.0, and R-3.4.4 software. Validation of genotype calling was performed by comparing the GSA with whole-genome sequencing (WGS) data of 56 non-PID controls. DNA samples of 95 clinically diagnosed PID patients, of which 60 patients (63%) had a genetically established diagnosis (by Next-Generation Sequencing (NGS) PID panels or Sanger sequencing), were analyzed to test the performance of the GSA. The additional SNVs detected by GSA were validated by Sanger sequencing. Results: Genotype calling of the customized array had an accuracy rate of 99.7%. The sensitivity for detecting rare PID variants was high (87%). The single sample replication in two runs was high (94.9%). The customized GSA was able to generate a genetic diagnosis in 37 out of 95 patients (39%). These 37 patients included 29 patients in whom the genetic variants were confirmed by conventional methods (26 patients by SNV and 3 by CNV analysis), while in 8 patients a new genetic diagnosis was established (6 patients by SNV and 2 patients suspected for leukemia by CNV analysis). Twenty-eight patients could not be detected due to the limited coverage of the custom probes. However, the diagnostic yield can potentially be increased when newly updated variants are added. Conclusion: Our robust customized GSA seems to be a promising first-line rapid screening tool for PIDs at an affordable price, which opens opportunities for low-cost genetic testing in developing countries. The technique is scalable, allows numerous new genetic variants to be added, and offers the potential for genetic testing not only in PIDs, but also in many other genetic diseases.

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.