Original Article
Health-Related Quality of Life in Children and Adults with Primary Immunodeficiencies: A Systematic Review and Meta-Analysis

https://doi.org/10.1016/j.jaip.2019.02.013Get rights and content

Background

Primary immunodeficiency diseases (PIDs) are a group of diseases that have been found to have an adverse impact on quality of life and health-related quality of life (HRQOL).

Objective

To systematically assess available evidence on the HRQOL of patients with PID.

Methods

We performed a literature search of all studies reporting HRQOL assessments in patients with PID published in English from inception to April 11, 2017, using MEDLINE and EMBASE.

Results

Of 1699 articles, 37 met the inclusion criteria. HRQOL was assessed by using various generic instruments. Child Health Questionnaire - Parent Form 50 and short-form 36 were the most frequently used (for children and adults, respectively). No PID-specific HRQOL instruments were used for children. HRQOL is significantly lower in adults with PID (mean score difference, −24.46; 95% CI, −34.57 to −14.34) and children (−10.06; 95% CI, −12.95 to −7.17) compared with the reference population and lower than in patients with other chronic conditions. There is a general agreement between child- and parent-reported data, although parents report child school-related HRQOL as more impaired than do children (6.19; 95% CI, 0.38 to 11.99). Most studies were of low to moderate quality and had methodological limitations.

Conclusions

Available evidence suggests that patients with PID have a lower HRQOL than do healthy individuals and patients with other chronic conditions, including diabetes mellitus and juvenile idiopathic arthritis. No disease-specific instruments are available for children, and few options are available for adults. This finding highlights the need for developing PID-specific instruments that would allow for a more sensitive evaluation of PID impact on patient health and psychological well-being, school/work, and social activities.

Introduction

Primary immunodeficiency diseases (PIDs) are a heterogeneous group of inherited disorders with no less than 300 genetically defined single-gene inborn errors of immunity detected to date.1 Recent data suggest that PID prevalence is much higher than generally thought, with around 6 million people living with a PID worldwide.2 Patients with PID are generally more prone to develop respiratory and gastrointestinal recurrent infections and/or autoimmune diseases.3

PID significantly influences patient life, limiting their working ability and physical and social activities.4, 5 This group of conditions has been linked with a number of negative effects on physical state6, 7 and social activities8 and is associated with increased anxiety9 and fatigue.10 Health-related quality of life (HRQOL) in patients with PID can be also significantly adversely impacted by delays in diagnosis and in treatment for infections.11

HRQOL is not assessed as often as it should be, despite the concept being widely used in research articles.12 Survival rate and number of disease exacerbations are the most frequently used outcome criteria in clinical trials; however, more recently, there has been increasing interest in HRQOL in PID.13 Within other chronic conditions, HRQOL is widely used as one of the most important outcomes in patient-reported outcome measures (PROMs), and is now an essential part of clinical trials, addressing issues of patient satisfaction, compliance with treatment, and treatment preferences. PROMs are normally designed to measure a specific concept in a standardized way, providing a means of quantifying qualitative information.12

HRQOL measures are inherently multidimensional and can be generic or disease specific. A generic measure is a broad outcome indicator including physical, mental, and social health; a specific measure is used to assess the impact of a disease or condition. Generic measures can be used to compare across different types of diseases but often lack the sensitivity or responsiveness needed to pick up small but important changes following an intervention or medical treatment. Evidence shows that HRQOL measures developed specifically for a particular condition are more reliable indicators of the positive and negative impact of that disease and treatment than is clinical opinion or the measurement of objective symptoms.14

Despite an increasing number of articles on HRQOL in patients with PID, far too little attention has been paid to the systematic evaluation of available data. The aim of this systematic review was to provide up-to-date evidence on the HRQOL of patients with PID, on qualitative analysis of actual information, and on identification of the strengths and weaknesses in existing approaches to HRQOL assessment. It is hoped that our findings will provide an impetus for further research in the field and improve our understanding of patient needs.

Section snippets

Search strategy

We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement for Reporting Systematic Reviews and Meta-Analyses (www.prisma-statement.org).15 The review was registered with the National Institute for Health Research's PROSPERO (CRD42017062380). Studies were identified through comprehensive literature searches of OVID MEDLINE and Embase databases from inception to April 11, 2017, using both free text and medical subject headings (MESH) terms. The search

Synthesis

The initial searches found 1699 publications; after removing duplicates (n = 259), 1440 records were identified, and titles and abstracts were screened. Of these, 43 met the inclusion criteria and were eligible for full-text assessment. Six studies were further excluded (Figure 1), with 37 articles included in the qualitative synthesis. Overall, 23 observational4, 6, 7, 8, 9, 10, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 and 14 interventional5, 38, 39, 40, 41, 42, 43, 44

Discussion

HRQOL has been found to predict and influence processes and health outcomes and has therefore become an important outcome in medical care and in clinical trials. This systematic review found evidence that HRQOL in children and adults with PID is more adversely impacted than in healthy individuals and people with other chronic conditions, including diabetes mellitus and juvenile idiopathic arthritis. There was general agreement between child- and proxy-reports of HRQOL in PID, except in a

Conclusions

In this systematic review we found that HRQOL in adults and children with PID is more impaired compared with that in healthy individuals and in patients with diabetes mellitus and juvenile idiopathic arthritis. Overall, the quality of the studies was poor to moderate. Recommendations to improve future research include a clear descriptive of the sample, the development and use of disease-specific measures, the use of both parent- and child-report measures where appropriate, longitudinal design

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    Conflicts of interest: I. Quinti received consultancy fees from receipt of consultation fees and grants by Shire, CSL Behring, Octapharma, and Kedrion. O. Blyuss acknowledges support from Russia (grant no. 074-02-2018-330). A. Dunn Galvin serves as a consultant for DBV Technologies and Aimmune Therapeutics. D. Munblit has received consultancy payment from Dairy Goat Co-Operative (NZ) Ltd; has given paid lectures for Merck Sharp & Dohme and Bayer; and also acknowledges the reception of funding from the «5-100» Russian Academic Excellence Project. The rest of the authors declare that they have no relevant conflicts of interest.

    These authors contributed equally to this work.

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