Fatigue and the wear-off effect in adult patients with common variable immunodeficiency

Abstract

Patients with common variable immunodeficiency (CVID) have increased fatigue compared with the general population. Fatigue is associated with lower quality of life (QoL), which is associated with higher mortality in CVID. This study aimed to determine the prevalence of self-reported fatigue for patients with CVID and to identify its possible drivers and burden on QoL. We analysed data from the 2013 Immune Deficiency Foundation (IDF) treatment survey. Answers were included from 873 CVID patients who responded (respondents). Of the 873 respondents included in the analysis, 671 (76·9%) reported fatigue, of whom 400 (83·7%) were receiving intravenous (i.v.) immunoglobulins (IVIG) and 271 (68·6%) were receiving subcutaneous (s.c.) immunoglobulins. This difference in fatigue between patients receiving IVIG and SCIG was statistically significant (P < 0·001). Dose and frequency of immunoglobulin replacement therapy (IgGRT) did not affect fatigue prevalence. Fatigued patients on IVIG reported greater infection rates and required more anti-microbials during the wear-off period. Fatigued patients reported worse health status than non-fatigued patients, and had lower rates of employment, education, household income and school attendance than their non-fatigued counterparts. Fatigue is increased in CVID, especially among patients receiving IVIG, compared to SCIG. Fatigue has a significant impact on QoL and productivity in patients with CVID. Further studies to identify the mechanisms of fatigue are warranted to help advance therapeutic measures to treat this disease and improve patients' QoL and wellbeing.

Keywords: Immune Deficiency Foundation; common variable immunodeficiency; fatigue; immunoglobulin replacement therapy; wear-off effect.

Figure 1

Relationship between fatigue and key patient demographics. (a) Relationship between fatigue and age: the prevalence of fatigue increased in a statistically significant manner with increasing age, starting from age 18 to age 64 years, and then decreased after age 65 years. (b) Relationship between fatigue and education level: fatigue is more prevalent in patients with an education level less than a college degree than it is in patients with a college degree or higher, *P = 0·002. (c) Relationship between fatigue and employment status: fatigue was more prevalent in unemployed patients than in employed patients. ‘Employed’ was defined as full‐ and part‐time employment. ‘Unemployed’ was defined as unemployed and disabled/too ill to work. ‘Other’ was defined as students, homemakers and other, *P < 0·001. (d) Relationship between fatigue and household income: the lower the household income, the higher the fatigue prevalence.

Figure 2

Numbers of upper respiratory tract infections during the past 12 months as stratified by presence of fatigue. Fatigue was more prevalent in patients reporting more frequent infections within the last 12 months. *P < 0·001, **P = 0·002, ***P = 0·001.

Figure 3

Relationships between fatigue in patients with common variable immunodeficiency (CVID) and mode of immunoglobulin G replacement therapy (IgGRT) received. (a) Fatigue prevalence is higher in intravenous immunoglobulin (IVIG) than in subcutaneous immunoglobulin (SCIG), *P < 0·001. (b) Fatigue prevalence by treatment frequency in SCIG; no significant differences in fatigue were found between weekly and bi‐weekly doses. (c) Fatigue prevalence by treatment frequency in IVIG; no significant differences in fatigue were found between weekly doses and doses received every 2, 3 or 4 weeks or more. (d) Fatigue by monthly dose in SCIG; no significant differences in fatigue were found between reported concentrations of monthly doses. (e) Fatigue by monthly dose in IVIG; no significant differences in fatigue were found between reported monthly doses. (f) Fatigue in SCIG as replacement versus immunomodulatory dose; no significant differences in fatigue were found as a function of replacement versus immunomodulatory dose. (g) Fatigue in IVIG as replacement dose versus immunomodulatory dose; no significant differences in fatigue were found in reported fatigue for IVIG a replacement dose versus an immunomodulatory dose.

Figure 4

Relationships between wear‐off effect and the infusion frequency. (a) Intravenous immunoglobulin (IVIG) wear‐off effect, reported as a function of infusion frequency; the number of days after infusion at which patients reported experiencing the wear‐off effect correlated with the frequency of the infusion. (b) Subcutaneous immunoglobulin (SCIG) wear‐off effect, reported as a function of infusion frequency; the number of days after infusion at which patients reported experiencing the wear‐off effect correlated with the frequency of the infusion.

Figure 5

Impact of fatigue on quality of life (QoL), perceived health status and missed work/school days. (a) Patient‐reported health status as a function of fatigue; fatigue was more frequently reported in patients with poor perceived health status than in those with good and very good/excellent perceived health status. (b) Effect of fatigue on missed work/school days; fatigued patients reported statically significantly higher number of missed work/school days than non‐fatigued patients, *P = 0·012.