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. 2018 Nov 12;13(1):201.
doi: 10.1186/s13023-018-0941-0.

The burden of common variable immunodeficiency disorders: a retrospective analysis of the European Society for Immunodeficiency (ESID) registry data

Irina Odnoletkova  1   2   3 , Gerhard Kindle  4   5 , Isabella Quinti  6   7 , Bodo Grimbacher  5   8 , Viviane Knerr  4   5 , Benjamin Gathmann  4   5 , Stephan Ehl  4   5 , Nizar Mahlaoui  9   10   11 , Philippe Van Wilder  12 , Kris Bogaerts  13   14 , Esther de Vries  15   16 ; Plasma Protein Therapeutics Association (PPTA) Taskforce
Collaborators, Affiliations

The burden of common variable immunodeficiency disorders: a retrospective analysis of the European Society for Immunodeficiency (ESID) registry data

Irina Odnoletkova et al. Orphanet J Rare Dis. .

Abstract

Background: Common variable immunodeficiency disorders (CVID) are a group of rare innate disorders characterized by specific antibody deficiency and increased rates of infections, comorbidities and mortality. The burden of CVID in Europe has not been previously estimated. We performed a retrospective analysis of the European Society for Immunodeficiencies (ESID) registry data on the subset of patients classified by their immunologist as CVID and treated between 2004 and 2014. The registered deaths and comorbidities were used to calculate the annual average age-standardized rates of Years of Life Lost to premature death (YLL), Years Lost to Disability (YLD) and Disability Adjusted Life Years (DALY=YLL + YLD). These outcomes were expressed as a rate per 105 of the CVID cohort (the individual disease burden), and of the general population (the societal disease burden).

Results: Data of 2700 patients from 23 countries were analysed. Annual comorbidity rates: bronchiectasis, 21.9%; autoimmunity, 23.2%; digestive disorders, 15.6%; solid cancers, 5.5%; lymphoma, 3.8%, exceeded the prevalence in the general population by a factor of 34.0, 7.6, 8.1, 2.4 and 32.6, respectively. The comorbidities of CVID caused 8722 (6069; 12,363) YLD/105 in this cohort, whereas 44% of disability burden was attributable to infections and bronchiectasis. The total individual burden of CVID was 36,785 (33,078, 41,380) DALY/105. With estimated CVID prevalence of ~ 1/ 25,000, the societal burden of CVID ensued 1.5 (1.3, 1.7) DALY/105 of the general population. In exploratory analysis, increased mortality was associated with solid tumor, HR (95% CI): 2.69 (1.10; 6.57) p = 0.030, lymphoma: 5.48 (2.36; 12.71) p < .0001 and granulomatous-lymphocytic interstitial lung disease: 4.85 (1.63; 14.39) p = 0.005. Diagnostic delay (median: 4 years) was associated with a higher risk of death: 1.04 (1.02; 1.06) p = .0003, bronchiectasis: 1.03 (1.01; 1.04) p = .0001, solid tumor: 1.08 (1.04; 1.11) p < .0001 and enteropathy: 1.02 (1.00; 1.05) p = .0447 and stayed unchanged over four decades (p = .228).

Conclusions: While the societal burden of CVID may seem moderate, it is severe to the individual patient. Delay in CVID diagnosis may constitute a modifiable risk factor of serious comorbidities and death but showed no improvement. Tools supporting timely CVID diagnosis should be developed with high priority.

Keywords: Burden of disease; Common variable immunodeficiency; DALY; Diagnostic delay; Health economics; Primary antibody deficiency; Primary immunodeficiency.

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Conflict of interest statement

Ethics approval and consent to participate

All included patients signed a consent form for collection and use of their personal data for research purposes: https://esid.org/Working-Parties/Registry/Informed-Patient-Consent.

Consent for publication

All included patients signed a consent form giving their permission for the publication of the research results based on the analysis of the collected anonymised data: https://esid.org/Working-Parties/Registry/Informed-Patient-Consent.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Inclusion of cases in the Burden of CVID analysis
Fig. 2
Fig. 2
Registration rate of CVID patients in the ESID registry, per 1 million by country population
Fig. 3
Fig. 3
Annual average rate of Years of Life Lost to premature death, per 5-year age interval, over the period: 2004–2014. CVID cohort versus general population*. All causes, both sexes. *Source: Global Burden of Disease Studies, Western Europe: http://ghdx.healthdata.org/gbd-results-tool
Fig. 4
Fig. 4
Prevalence of non-communicable comorbidities. Average annual age-standardized prevalence rate per 100,000 over the period 2004–2014. CVID cohort versus general population*. All ages, both sexes. *Source: Global Burden of Disease Studies, Western Europe: http://ghdx.healthdata.org/gbd-results-tool
Fig. 5
Fig. 5
Prevalence of infections. Average annual age-standardized prevalence rate per 100,000 over the period 2004–2014. CVID cohort versus general population*. All ages, both sexes. *Source: Global Burden of Disease Studies, Western Europe: http://ghdx.healthdata.org/gbd-results-tool
Fig. 6
Fig. 6
Burden of disease to society: CVID versus top-ten health problems in Europe. Annual age-standardized DALY rate per 100,000 of general population*. *Source: Global Burden of Disease Studies, Western Europe 2015: http://ghdx.healthdata.org/gbd-results-tool
Fig. 7
Fig. 7
Burden of disease to individual patient: CVID versus top-ten health problems in Europe. Annual age-standardized DALY rate per 100,000 of diagnosed population*. *Calculated as DALY per 100,000 general population X 100,000/ disease prevalence per 100,000 general population
See this image and copyright information in PMC

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