Children and adults with primary antibody deficiencies gain quality of life by subcutaneous IgG self-infusions at home

Abstract

A large number of children and adults with primary antibody deficiencies need lifelong IgG replacement therapy. It is mostly unknown what effect the choice of replacement therapy has on the patients' health-related quality of life (HRQOL) and treatment satisfaction (TS).
To investigate whether a switch from hospital-based intravenous IgG (IVIG) to home-based subcutaneous IgG (SCIG) therapy would improve the HRQOL and TS.
Fifteen children (<14 years; hospital-based IVIG therapy at enrollment) and 32 adults (> or =14 years; 22 on hospital-based IVIG and 10 on home-based SCIG therapy at enrollment) were included. Questionnaires were completed at baseline and at 6 and 10 months: the Child Health Questionnaire-Parental Form 50 (children) or Short Form 36 (adults), the Life Quality Index, and questions regarding therapy preferences.
The SCIG home therapy was reported to give better health (P=.001) and improved school/social functioning (P=.02) for the children, reduced emotional distress (P=.02) and limitations on personal time for the parents (P=.004), and fewer limitations on family activities (P=.002). Adults switching therapy reported improved vitality (P=.04), mental health ( P=.05), and social functioning ( P=.01). Adults already on SCIG home therapy at enrollment retained high HRQOL and TS scores. The SCIG home therapy improved TS because it led to greater independence and better therapy convenience ( P <.05). The patients preferred the SCIG administration route and having the treatment at home.
Home-based SCIG therapy improves several important aspects of HRQOL and provides the patients with primary antibody deficiencies and their families with greater independence and better control of the therapy situation and daily life. SCIG home therapy is an appreciated therapeutic alternative for adults and children in need of lifelong IgG replacement therapy.

Full text

Original article
Children and adults with primary antibody
deficiencies gain quality of life by
subcutaneous IgG self-infusions at home
Ann Gardulf, RN, PhD,
a
Uwe Nicolay, Dipl Math,
a
Oscar Asensio, MD,
b
Ewa
Bernatowska, MD, PhD,
c
Andreas Bo¨ ck, MD,
d
Beatriz T. Costa-Carvalho, MD,
e
Carl
Granert, MD, PhD,
f
Stefan Haag, MD, PhD,
g
Dolores Herna
´ndez, MD, PhD,
h
Peter
Kiessling, PhD,
g
Jan Kus, MD, PhD,
i
Nuria Matamoros, MD, PhD,
j
Tim Niehues, MD,
PhD,
k
Sigune Schmidt, MD,
l
Ilka Schulze, MD, PhD,
m
and Michael Borte, MD, PhD
n
Stockholm, Sweden, Sabadell, Valencia, and Palma de Mallorca, Spain, Warsaw, Poland, Vienna,
Austria, Sa˜ o Paolo, Brazil, and Marburg, Du¨ sseldorf, Freiburg, Berlin, and Leipzig, Germany
Background: A large number of children and adults with
primary antibody deficiencies need lifelong IgG replacement
therapy. It is mostly unknown what effect the choice of
replacement therapy has on the patients’ health-related quality
of life (HRQOL) and treatment satisfaction (TS).
Objective: To investigate whether a switch from hospital-based
intravenous IgG (IVIG) to home-based subcutaneous IgG
(SCIG) therapy would improve the HRQOL and TS.
Methods: Fifteen children (<14 years; hospital-based IVIG
therapy at enrollment) and 32 adults (14 years; 22 on
hospital-based IVIG and 10 on home-based SCIG therapy at
enrollment) were included. Questionnaires were completed at
baseline and at 6 and 10 months: the Child Health
Questionnaire–Parental Form 50 (children) or Short Form 36
(adults), the Life Quality Index, and questions regarding
therapy preferences.
Results: The SCIG home therapy was reported to give better
health (P= .001) and improved school/social functioning
(P= .02) for the children, reduced emotional distress (P= .02)
and limitations on personal time for the parents (P= .004), and
fewer limitations on family activities (P= .002). Adults
switching therapy reported improved vitality (P= .04), mental
health (P= .05), and social functioning (P= .01). Adults already
on SCIG home therapy at enrollment retained high HRQOL
and TS scores. The SCIG home therapy improved TS because it
led to greater independence and better therapy convenience
(P< .05). The patients preferred the SCIG administration
route and having the treatment at home.
Conclusions: Home-based SCIG therapy improves several
important aspects of HRQOL and provides the patients with
primary antibody deficiencies and their families with greater
independence and better control of the therapy situation and
daily life. SCIG home therapy is an appreciated therapeutic
alternative for adults and children in need of lifelong
IgG replacement therapy. (J Allergy Clin Immunol
2004;114:936-42.)
Key words: Primary immunodeficiencies, subcutaneous IgG ther-
apy, intravenous IgG therapy, quality of life, home care, patient
satisfaction, self-care, nursing
Primary immunodeficiency diseases result from inborn
defects of the immune system. Most of these diseases
include a defective antibody formation (primary antibody
deficiency [PAD]), which leads to increased susceptibility
to bacterial infections of the mucous membranes, notably
of the sinopulmonary tract.
1
Many children and adults
with PAD need lifelong replacement therapy with IgG.
Rapid subcutaneous IgG (SCIG) infusions have been
shown to be easy to learn for both adult patients
2,3
and
children/parents
4,5
and to be safe, with no or few sys-
temic adverse reactions
2-10
and with no transmission of
the hepatitis C virus.
3
It results in normalized serum
From
a
the Swedish Centre for Immunodeficiencies, Division of Clinical
Immunology at the Department of Laboratory Medicine, Karolinska
Institutet at Karolinska University Hospital, Stockholm;
b
Servicio de
Immunologicia Clinica, Consorcio Hospitalari del Parc Tauli, Sabadell;
c
Children’s Memorial Health Institute, Department of Immunology,
Warsaw;
d
Universita¨tsklinik fu¨ r Kinder- und Jugendheilkunde, Vienna;
e
Department of Pediatrics, Division of Allergy, Clinical Immunology and
Rheumatology, Federal University of Sa˜o Paolo;
f
the Immunodeficiency
Unit, Section of Clinical Immunology, Karolinska University Hospital,
Stockholm;
g
ZLB Behring GmbH, Marburg;
h
Department of Allergy,
Hospital Universitario La Fe, Valencia;
i
National Research Institute of
Tuberculosis and Lung Diseases, Warsaw;
j
Servicio de Immunologia,
Hospital Universitario Son Dureta, Palma de Mallorca;
k
Universita¨tsklinikum Du¨ sseldorf Heinrich-Heine-University, Klinik fu¨r
Kinder-Onkologie, -Ha¨matologie und -Immunologie, Du¨ sseldorf;
l
Medizinische Universita¨tsklinik, Abteilung Rheumatologie und Klinische
Immunologie, Freiburg;
m
Charite´ Berlin, Humboldt-Universita¨ t, Klinik fu¨r
Pa¨diatrie mit Schwerpunkt Pneumologie/Immunologie, Berlin; and
n
Klinik
fu¨r Kinder- und Jugendmedizin am Sta¨ dtischen Klinikum "St Georg"
Leipzig, Akademisches Lehrkrankenhaus der Universita¨t Leipzig, Leipzig.
Supported by ZLB Behring GmbH, Marburg, Germany (formerly Aventis
Behring GmbH).
Disclosure of potential conflict of interest: The local study coordinators
received honoraria and/or travel grants from Aventis Behring GmbH,
Marburg, Germany. At the time of the study, U. Nicolay, S. Haag, and P.
Kiessling were employed by Aventis Behring GmbH.
Received for publication December 20, 2003; revised June 13, 2004; accepted
for publication June 29, 2004.
Reprint requests: Ann Gardulf, Karolinska University Hospital, Huddinge,
M96, SE-141 86 Stockholm, Sweden. E-mail: ann.gardulf@labmed.ki.se.
0091-6749/$30.00
Ó2004 American Academy of Allergy, Asthma and Immunology
doi:10.1016/j.jaci.2004.06.053
936
Basic and clinical immunology

Abbreviations used
CHQ-PF50: Child Health Questionnaire–Parental Form 50
HRQOL: Health-related quality of life
IVIG: Intravenous IgG
LQI: Life Quality Index
PAD: Primary antibody deficiency
SCIG: Subcutaneous IgG
SF-36: Short Form 36
TS: Treatment satisfaction
IgG concentrations
2-6,10
corresponding to those seen in
intravenous IgG (IVIG) replacement therapy and with as
few infections as during IVIG therapy.
7
Data regarding self-reported outcomes in the health-
related quality of life (HRQOL) due to PAD and its
replacement therapy are rare in adults
11
and lacking in
children and their families. The aims of the study were
therefore to describe self-reported HRQOL and treatment
satisfaction (TS) in children and adults with PAD and to
investigate whether the introduction of SCIG replacement
therapy as self-infusions at home would improve the
HRQOL and TS.
METHODS
Patients
The inclusion criteria were a diagnosis of PAD according to
definition,
1
age between 2 and 75 years, IVIG or SCIG replacement
therapy for at least 6 months, stable serum IgG trough levels (5g/L)
before enrollment, no other major chronic diseases, and an ability and
willingnessto answer questionnaires. Sixty eligible patientsat 12 study
sites in 6 countries were invited, and 58 agreed to participate. The
participants were divided into 2 groups—those younger than 14 years
(referred to as children; n = 17 at enrollment) and those 14 years or
older (adults; n = 41)—according to recommendations from the au-
thors of the 2 generic HRQOL questionnaires used for the study.
12,13
Medical data regarding the participants are shown in Table I.Thirty-
seven patients received hospital-based IVIG at enrollment, and 10
patients already used SCIGself-infusions at home. The mainreason for
including patients already receiving SCIG was that these patients, who
had a long experience with self-administered SCIG therapy at home,
served as controls to gauge the study-specific effects. The mean IgG
trough leveldirectly before the study start was 7.9 g/L (range, 5.5-11.9
g/L) for the children. For the adults, the corresponding figures were 8.3
g/L (range, 5.9-15.8 g/L) for those on IVIG therapy at enrollment and
9.0 g/L (range, 6.6-14.2 g/L) for those on SCIG therapy at enrollment.
The participants answered the questionnaires thrice: at baseline
and after 6 and 10 months. Not all the participants filled in all the
questionnaires. However, in no case was the failure to complete the
questionnaires attributed to the health of the participants (Table I).
SCIG therapy
The IgG was given as weekly infusions by using a technique
described previously.
2-7,9,10
Each participant completed 43 infusions
(10 months) with a liquid pasteurized polyvalent human 16% (160
mg/mL) IgG preparation intended for subcutaneous use (ZLB
Behring GmbH, Marburg, Germany [formerly Aventis Behring
GmbH, Marburg, Germany]). The patients continued with a dosage
equivalent to the dosage during the previous IgG replacement therapy.
Weekly dosages ranged between 50 and 150 mg/kg body weight.
Home therapy
All participants were trained and supervised once per week at the
local hospital for 4 to 6 training sessions and had to show practical
skill, knowledge, and confidence in the SCIG administration route
before being transferred to self-infusions at home. The parents gave
the infusions to their children or supervised the treatment. The
participants visited their clinic every fourth week for medical and
nursing follow-ups and to verify that the infusion technique was
correct.
Questionnaires: HRQOL
The Child Health Questionnaire–Parental Form 50 (CHQ-PF50)
12
was used for the children and answered by the parents. It focuses on
the physical and psychosocial functioning and well-being of the child
and his or her family and aggregates to 15 concepts in total (Table II).
For this study, the 1 stand-alone global item ‘‘change in health’’ was
not used because it has a 1-year recall period. Higher scores indicate
a better HRQOL.
Short Form 36 (SF-36) was used for the adults. It consists of 35
items forming 8 subscales: physical function (10 items), role-physical
(4 items), bodily pain (2 items), general health (5 items), vitality (4
items), social function (2 items), role-emotional (3 items), and mental
health (5 items).
13,14
As in the CHQ-PF50, the 1-year comparison of
health was excluded. Higher scores indicate a better HRQOL.
TABLE I. Demographic and medical patient data
Variable
Children
(<14 y)
Adults
(14 y)
No. patients enrolled 17 41
No. evaluable patients 15*32à§k
Sex (male/female) 15/0 20/12
Age (y)
Median 7 33.5
Range 3-13 14-74
Diagnosis (No. patients)
CVID 3 25
IgG subclass deficiency 2 0
Other hypo- or
gamma globulinemia
10 7
IgG therapy at enrollment
(No. patients)
Intravenous IgG 15 22
Subcutaneous IgG 0 10
Serum IgG trough levels
before study, mean (range)
7.9
(5.5-11.9)
8.3
(5.9-15.8)
9.0
(6.6-14.2){
CVID, Common variable immunodeficiency.
*Two children were excluded from the final evaluation because of belated
assessments (baseline, n = 1; 6 months, n = 1).
Study sites and number of patients evaluated: Brazil, children n = 0/adults
n = 3; Germany, n = 6/n = 13; Poland, n = 9/n = 4; Spain, n = 0/n = 2;
Sweden, n = 0/n = 10.
àFive adults were excluded from final evaluation because of belated
assessments (baseline, n = 1; 6 months, n = 2; 10 months, n = 2).
§Three adults prematurely discontinued the study before the 6-month
assessment (1 protocol violation [ie, a patient with renal failure was
wrongly included], 1 suspected systemic adverse reaction in a patient with
a history of such reactions during IVIG infusions, and, in 1 case, missed
follow-ups because of a long stay abroad).
kOne adult did not complete the questionnaires at the 10-month
assessment.
{Adults on subcutaneous IgG therapy at enrollment.
J ALLERGY CLIN IMMUNOL
VOLUME 114, NUMBER 4
Gardulf et al 937
Basic and clinical immunology

Treatment satisfaction
The Life Quality Index (LQI) was developed for a study regarding
PAD patients receiving IVIG infusion therapy at the clinic or at
home.
15
The LQI examines the respondent’s perceptions of the
impact of the IgG treatment on daily activities. The LQI is worded
without reference to home- or clinic-based setting. The original LQI
was slightly modified; ie, the wording ‘‘IVIG treatment’’ was
changed to ‘‘SCIG treatment.’’ Furthermore, in the version for the
parents, the statements were modified to ask for the perceptions of
the SCIG treatment in relation to ‘‘my child.’’ The LQI consists of
15 statements, each rated on a 7-point Likert response scale. A
maximum summary score of 105 indicates the highest possible
satisfaction with factors such as independence, therapy convenience,
social/school/work activities, and health and travel costs. In addition
to the LQI, 2 preference items were used: ‘‘Which IgG therapy do
you prefer?’’ (IVIG, SCIG, or no preference) and ‘‘Where do you
prefer to receive your IgG therapy?’’ (in the hospital/in the doctor’s
office, at home, or no preference).
Translation of the questionnaires
When available, linguistically validated translations of the instru-
ments were used. Where validated translations were not available, the
translation process followed the standard for the translation of
HRQOL instruments (forward-backward translation processes).
16
Assessments
The CHQ-PF50 or the SF-36, the LQI, and questions about
demographic background characteristics were completed at baseline.
At 6 and 10 months, the 2 ‘‘preference’’ items were added. The set of
questionnaires was answered at the hospitals by the adult patients
themselves or by the parents.
Statistical analysis
The primary analyses included the children (n = 15) and adults
(n = 32) who were fully compliant with the study protocol. However,
second-line analyses were also performed on the basis of the 2 entire
populations of children (n = 17) and adults (n = 41) to explore
whether the exclusion of noncompliant participants resulted in
a biased comparison. The comparisons of the data at 10 months with
baseline did not reveal relevant qualitative differences between the
entire and the final populations with regard to any of the question-
naires. Thus, restriction of the analyses to the compliant participant
populations did not lead to biased estimates.
The nonresponder rate to single items was very low (in total,
0.43%). Still, to handle missing data, 2 methods were used. If
less than 50% of the responses within a single scale were missing
for a respondent, item imputation was performed by mean value
substitution as described in the scoring manuals.
12,14
Otherwise,
values were predicted by using an explicit regression model
17
that
included the previously observed scores on the scale for the
individual as well as important covariates (age, country, route of
previous IgG treatment, and number of SCIG infusions).
Data were analyzedwith a repeated-measures model
18
that assumes
correlated assessments over time and normally distributed response
variables. Separately for children and adults, 6- and 10-month assess-
ments were compared with the patients’ baselines. Statistical analysis
was performed with SAS version 8.2 (SAS Institute Inc, Cary, NC).
TABLE II. Concepts measured in the CHQ-PF50
Concept Abbreviation No. items Definition
Physical functioning PF 6 Limitations in physical activities
Role/social–emotional, behavioral REB 3 Limitations in school, work, or social activities
because of emotional or behavioral problems
Role/social–physical RP 2 Limitations in school, work, or social activities
because of physical problems
Bodily pain BP 2 Intensity/frequency of pain/discomfort
Behavior BE 6*Ability to get along with others, behavioral
problems including aggression, delinquency,
impulsivity, and social withdrawal
Mental health MH 5 Positive and negative states including anxiety,
depression, and positive affect
Self-esteem SE 6 Satisfaction with school, athletic ability,
appearance, ability to get along with others
General health perceptions GH6*Perceptions of overall health and illness
Parental impact–emotional PE 3 Distress and worry experienced by parents
concerning child’s condition
Parental impact–time PT 3 Limitations in personal time experienced by
parents because of child’s condition
Family activities FA 6 Limitations and interruptions in usual family
activities and family tension as a result of the
child’s health
Family cohesion FC1 Ability of family members to get along with
one another
Global health GGH1*Overall health of the child
Global behavior GBE1*Overall behavior as compared with other children
of the same age
Change in health CHà1 Change in child’s health as compared with 1 y ago
*The subscale BE also includes the single-item scale GBE and the subscale GH the single-item scale GGH leading to a total of 52 items counted for the table.
A 4-week recall period was used for all concepts except for GH, FC, GGH, and GBE, for which ‘‘in general’’ is used instead.
àThe CH item was not used for this study.
J ALLERGY CLIN IMMUNOL
OCTOBER 2004
938 Gardulf et al
Basic and clinical immunology

Ethics
All adult patients and the children’s parents were given oral and
written information in their own languages, and written informed
consent was obtained from all study participants. The local ethics
committee at each participating hospital approved the study before
any patient was informed and enrolled.
RESULTS
HRQOL: CHQ-PF50
Significant improvements were found for 6 of the CHQ-
PF50 subscales at 10 months compared with baseline.
Between 47% and 87% of the 15 children showed an
improvement of at least 5 points with regard to these
scales. Four of these significant improvements were
already seen after 6 months (Table III).
HRQOL: SF-36
The 22 adults on IVIG at enrollment reported signifi-
cantly improved vitality (baseline mean, 62.8; 10-month
mean, 70.2; P= .04), mental health (baseline mean, 87.5;
10-month mean, 94.3; P= .05), and social functioning
(baseline mean, 77.7; 10-month mean, 83.2; P= .01) at 10
months. The proportion of IVIG adults with an improve-
ment of at least 5 points was 50%, 32%, and 32%,
respectively, for the 3 scales. The 10 adults on SCIG at
enrollment reported high SF-36 scores already at baseline,
and no significant changes were seen over time (data not
shown).
TS: LQI
For the children, the total mean summary LQI score
significantly improved from 73.4 613.4 at baseline to
94.9 68.7 at 10 months (P= .0001; Fig 1). For the adults
on IVIG therapy at enrollment, the total mean summary
LQI score improved from 82.2 615.0 to 93.7 69.0
(P= .0012). Sixty percent of the children and 50% of the
adults reported an increase of at least 10 points. The adults
on SCIG therapy at enrollment reported a high total mean
summary LQI score already at baseline (95.6 610.7), and
no significant change was seen over time (94.5 68.8 at 10
months; Fig 1).
Preference items
All children and their parents and all 10 adults on SCIG
therapy at enrollment reported that they preferred the
SCIG self-infusions at home. Sixteen (73%) of the 22
adults on IVIG at enrollment reported that they preferred
the SCIG self-infusions at home. Two reported that the
continuation of SCIG therapy was most important, but
they had no preference regarding setting. Two patients had
no preference regarding the IgG administration route but
wanted to continue with home therapy. One patient
reported no preference regarding either IgG administra-
tion route or setting, and 1 patient preferred IVIG therapy
at the hospital.
DISCUSSION
HRQOL is a subjective perception of the effect of
health status (including disease and treatment) on physi-
cal, psychological, and social functioning and well-
being.
19,20
Children and adults with PAD have a chronic
condition and in most cases are faced with the prospect
of lifelong IgG treatment. Surprisingly, only 1 study
11
using standardized, validated, generic HRQOL instru-
ments has been presented with patient-reported data
regarding HRQOL in adults. In this study, the HRQOL
and TS of children with PAD and their families have been
addressed for the first time.
TABLE III. Results of the CHQ-PF50 before and during SCIG self-infusions at home
Pvalues
Concept*Baseline (mean SD) 6 mo (mean SD) 10 mo (mean SD) 6 mo vs BL 10 mo vs BL
PF 90.4 611.4 91.5 625.8 90.4 616.1 NS NS
REB 79.5 625.6 83.0 632.8 95.6 610.1 NS .02
RP 85.6 623.5 86.7 630.3 92.2 618.8 NS NS
BP 80.0 623.9 78.0 622.7 88.7 617.3 NS NS
BE 67.3 616.2 69.0 620.0 72.4 616.5 NS NS
MH 70.8 619.4 71.3 620.0 76.3 613.9 NS NS
SE 80.5 611.0 77.2 616.2 82.2 615.4 NS NS
GH 36.1 613.4 51.3 615.3 53.7 611.5 .01 .001
PE 52.8 627.4 68.9 627.4 72.8 624.5 .05 .02
PT 64.4 628.8 71.9 626.8 81.5 620.9 NS .004
FA 68.1 620.1 77.8 621.2 85.6 616.4 .04 .002
FC 67.3 617.3 70.3 621.0 76.0 614.0 NS NS
GGH 55.0 623.6 77.8 611.3 78.7 614.6 .008 .01
GBE 69.7 616.6 69.0 622.8 69.7 621.9 NS NS
BL, Baseline; NS, not significant.
*Explanations of the abbreviations of the concepts are given in Table II. Higher scores indicate better physical or psychosocial functioning or less effect on the
family situation because of a disease.
J ALLERGY CLIN IMMUNOL
VOLUME 114, NUMBER 4
Gardulf et al 939
Basic and clinical immunology

The parents reported significant improvements for 6
of the 14 subscales in the CHQ-PF50. The improve-
ments were seen in areas related to the children’s social
functioning and health, the parents’ own life situation, and
family functioning. After the introduction of the SCIG
home-therapy regimen, the parents reported improved
school and social functioning for their child (subscale role/
social–emotional, behavioral) and improved overall
health (global health); they also reported that the child
now was as healthy as other children and that the child
had a better resistance against infections (general health
perceptions). Moreover, the parents had greater expect-
ations for a healthier life of the child in the future (general
health perceptions).
From this study, is it not possible to say whether the
reported improvements in the children’s health were
primarily related to the use of the SCIG therapy itself,
the switch to home therapy, or both. The main goal with
any IgG replacement therapy is to achieve normalized
serum IgG levels and, thereby, a reduced frequency and
severity of infections. One inclusion criterion for the study
was a serum IgG trough level of >5 g/L for at least
6 months before enrollment. In the children, the serum
IgG trough levels ranged between 5.5 and 11.9 g/L at
enrollment and remained high (data not shown). The
stable day-by-day serum IgG concentrations demonstrated
between SCIG infusions
21,22
may have contributed to
a better resistance against infections and, thereby, the
better health status of the children. The SCIG administra-
tion route also avoids unphysiologically high serum IgG
peak levels, as are commonly observed after IVIG
infusions; these are suspected to trigger systemic side
reactions such as headache. Another benefit from the
home-therapy regimen itself was the reduced number of
visits to the hospital for the PAD children and a decreased
risk for the children to acquire infections. This may
contribute to the reported improved health of the PAD
children and may also reduce the parents’ anxiety that their
child may become infected. Indeed, in this study it was
found that the introduction of the SCIG home therapy
made the parents feel less worried or concerned regarding
their child’s physical health and emotional well-being
(subscale parental impact–emotional).
The parents also reported that the introduction of the
home therapy resulted in less limitation in personal time
for their own needs (parental impact–time). Moreover, the
home-therapy regimen positively influenced the entire
family situation, eg, fewer restrictions and interruptions
in the usual family activities (family activities). Home
therapy has been considered especially important in pe-
diatric immunodeficiency care because it saves the
families the trips to the hospital,
4
and families have
reported that they prefer the shorter, more frequent
infusions at home to the more disruptive and lengthy
visits to a hospital every third to fourth week as required
by IVIG infusions.
5
For the adults on IVIG therapy at enrollment, improve-
ments in HRQOL as measured by the SF-36 were also
seen (vitality, mental health, and social functioning) after
the switch to SCIG home therapy. This was in contrast to
the adults already on SCIG home therapy, in whom high
scores for these 3 scales were already seen at enrollment.
The vitality scale captures the subjective well-being in
relation to energy level and fatigue, the mental health scale
captures different aspects of psychological well-being,
and the social functioning scale captures both the quantity
FIG 1. Life Quality Index scale (range, 15-105). A maximum summary score of 105 indicates the highest
possible satisfaction with the effect of any IgG replacement therapy on factors such as independence, therapy
convenience, social/school/work activities, and health and travel costs. Data are given as self-reported
summary scores for children and adults at baseline and at 6 and 10 months. *P<.05 (F test at 10 months vs
baseline).
J ALLERGY CLIN IMMUNOL
OCTOBER 2004
940 Gardulf et al
Basic and clinical immunology

and quality of social activities.
14
It has previously been
shown that adult patients with common variable immu-
nodeficiency who are not yet treated with IgG replace-
ment therapy report significantly pronounced fatigue,
restrictions in social and leisure activities, and poorer
psychological well-being compared with healthy individ-
uals.
11
Also, adults on hospital-based therapy with
adequate dosages of IVIG infusions or intramuscular
IgG injections reported significantly decreased physiolog-
ical well-being and pronounced fatigue compared with
healthy individuals. The introduction of SCIG home
therapy was, in both the untreated and the previously
IVIG-treated or intramuscular IgG–treated adults, found to
result in a significant improved HRQOL and decreased
fatigue.
11
It has been stated by the patients that the
introduction of home therapy leads to independence,
a sense of freedom and flexibility, and a reduced sense
of being sick or disabled.
23
Introduction of home therapy
programs seems to have a major beneficial effect on the
patients’ psychological well-being and vitality. This in
turn may lead to an increased courage for welcoming
social contacts and activities—something otherwise
avoided by PAD patients because of tiredness and fear
of acquiring infections.
11
The increased vitality reported in both this study and in
the previous HRQOL study
11
after the introduction of the
weekly SCIG therapy is of interest in relation to the
ongoing discussion regarding the possible benefit of the
stable between-infusion serum IgG levels seen during
SCIG therapy.
21,22
It is known that the use of monthly
IVIG therapy results in fluctuations in serum IgG con-
centrations,
24
and patients often complain of increased
tiredness and worsened well-being in the week before
the next infusion. The increased infusion frequency with
the weekly SCIG therapy has been found to result in
a trend to a higher IgG trough level
7
and a day-by-day
serum IgG curve that better corresponds to the normal
endogenous IgG production.
22
The stable serum IgG level
between weekly SCIG infusions may indeed be one
contributing factor to the improved vitality reported by
the patients.
The introduction of the home-therapy program also led
to increased TS, as measured by the LQI, for children and
adults switching from hospital-based to home-based
therapy. The adults on SCIG home therapy at enrollment
already reported a high total mean summary LQI score
at baseline. The LQI showed that home therapy resulted
in greater independence, with less disruption of daily
activities; less effect on school, work, and social activities;
freedom to travel; better therapy convenience; comfort;
treatment flexibility; and pleasantness of treatment atmo-
sphere. The concept of feeling able to control a treatment
is important for the patient because a sense of active
participation leads to greater compliance and improved
medical outcome.
15
Also, home-based IVIG therapy is a patient-appreciated
option in some countries. In a study from the United
States, it was shown that the switch from hospital-based
IVIG to home-based IVIG therapy improved the TS of the
included children and adults.
15
However, different patient
selection criteria must be used for IVIG self-infusions at
home, and this reduces the number of individuals who can
benefit from home therapy.
The home-therapy regimen, whether SCIG or IVIG, has
also a beneficial effect on the direct and indirect costs of
the society and of the individual patient and family. For the
families in this study, the child and at least 1 parent had to
visit the hospital for IVIG therapy an average of every
third week, ie, seventeen 1-day visits per year. For the 15
children in this study alone, the production loss for the
accompanying adults amounted to 225 days. The parents
may also have to take time off from work with salary
reductions and also pay for the travel costs and possible
fees at the hospital. Once in home therapy, no time off
from school for the child or work for the parent is needed.
Instead the infusion can be given at a suitable time for
the family, for example, during the evening when watch-
ing television, when the child is busy playing, or during
dinner. It has been shown that SCIG therapy at home
substantially reduces society and health-care costs
3
and
cuts the direct and indirect costs of the patients by half.
25
The study design was derived from the European
Committee for Proprietary Medicinal Products guidelines
for intravenous
26
and subcutaneous and intramuscular
27
use of immunoglobulins. Both guidelines recommend that
IgG replacement therapy be studied in a longitudinal
design for at least 6 months. To have more reliable data,
we expanded the European Union recommendation by
treating more patients and for 10 months with weekly
SCIG. The study was designed as an open prospective
evaluation that used each participant as his or her own
control in comparing baseline HRQOL data with the data
reported at the final evaluation after 10 months. The
follow-up time for this study was 10 months, and this must
be considered a short period in which to study the effect of
a treatment on HRQOL and daily activities. However,
already after 6 months the parents and the adult patients
reported significant improvements in HRQOL. We cannot
completely rule out the possibility that the improvements
in HRQOL and TS were, to some extent, results from
study effects. However, most likely, the reported changes
can be attributed to the switch from the hospital-based to
the home-based therapy; otherwise, the patients who had
already been on SCIG before enrollment in the study
should also have exhibited a further improvement with
regard to their HRQOL and TS, but this did not occur.
For children and adults with PAD, lifelong IgG re-
placement therapy aims at reducing the frequency and
severity of infections and the subsequent fatigue and lack
of energy. A successful IgG treatment and support should
provide the patient with a feeling of increased resistance to
infections and, thereby, the courage, strength, and will-
ingness to participate in social and family activities. In this
study, it was found that several aspects of the HRQOL and
the TS improved when children and adults with PAD
changed from a staff-run, hospital-based IVIG therapy
program to a staff-supported, patient- or parent-run, home-
therapy program with SCIG self-infusions. A successful
J ALLERGY CLIN IMMUNOL
VOLUME 114, NUMBER 4
Gardulf et al 941
Basic and clinical immunology

home-therapy regimen must be based on interactive
patient/family education programs and continuous sup-
port.
23,28,29
The easy SCIG administration technique gives
most adult patients and children or parents the opportunity
to manage their own IgG treatment. On the basis of the
results from this study and previous evaluations of the
SCIG administration route showing safety,
2-10
normalized
serum IgG trough levels,
2,3,6,7,10,21,22
protection against
infections,
7
patient preference for home therapy,
4,5,11,15,23
and the easy infusion technique, SCIG home therapy is
strongly advocated as a therapeutic alternative for adults
and children in need of lifelong IgG replacement therapy.
We are grateful to all the nurses at the local study centers who
helped with the study by training and supervising the patients and by
collecting blood samples and questionnaires. We sincerely thank
Sylvia Herget (data collection and database handling) and Dirk
Spruck (statistical analyses) at Covidence GmbH, Marburg,
Germany. We also thank Neil Tomkinson, Preston, England, for
his help with the language revision.
REFERENCES
1. Rosen FS, Eibl M, Roifman C, Fischer A, Volanakis J, Aiuti F, et al.
Primary immunodeficiency diseases. Report of an IUIS scientific
committee. Clin Exp Immunol 1999;118(suppl 1):1-28.
2. Gardulf A, Hammarstro¨m L, Smith CIE. Home treatment of hypogam-
maglobulinaemia with subcutaneous gammaglobulin by rapid infusion.
Lancet 1991;338:162-6.
3. Gardulf A, Andersen V, Bjo¨rkander J, Ericson D, Frøland SS, Gustafson
R, et al. Subcutaneous immunoglobulin replacement in patients with
primary antibody deficiencies: safety and costs. Lancet 1995;345:365-9.
4. Abrahamsen TG, Sandersen H, Bustnes A. Home therapy with sub-
cutaneous immunoglobulin infusions in children with congenital immu-
nodeficiencies. Pediatrics 1996;98:1127-31.
5. Gaspar J, Gerritsen B, Jones A. Immunoglobulin replacement therapy by
rapid subcutaneous infusions. Arch Dis Child 1998;79:48-51.
6. Thomas MJ, Brennan VM, Chapel HM. Rapid subcutaneous immuno-
globulin infusions in children. Lancet 1993;342:1432-3.
7. Chapel HM, Spickett GP, Ericson D, Engl W, Eibl M, Bjo¨ rkander J. The
comparison of the efficacy and safety of intravenous versus subcutaneous
immunoglobulin replacement therapy. J Clin Immunol 2000;20:94-100.
8. Hansen S, Gustafson R, Smith CIE, Gardulf A. Subcutaneous IgG
infusions in patients with primary antibody deficiencies: decreased time
of delivery with maintained safety. Clin Immunol 2002;104:237-41.
9. Gustafson R, Gardulf A, Granert C, Hansen S, Hammarstro¨m L.
Prophylactic therapy for selective IgA deficiency. Lancet 1997;350:865.
10. Radinsky S, Bonagura VR. Subcutaneous immunoglobulin infusion as an
alternative to intravenous immunoglobulin. J Allergy Clin Immunol
2003;112:630-3.
11. Gardulf A, Bjo¨ rvell H, Gustafson R, Hammarstro¨m L, Smith CIE. The life
situation of patients with primary antibody deficiency untreated or treated with
subcutaneous gammaglobulin infusions. Clin Exp Immunol 1993;92:200-4.
12. Landgraf J, Abetz L, Ware JE Jr. The Child Health Questionnaire (CHQ),
a user’s manual. 2nd ed. Boston: The Health Institute; 1999.
13. Ware JE, Sherbourne CD. The MOS 36-item short form health survey
(SF-36). I. Conceptual framework and item selection. Med Care 1992;30:
473-83.
14. Ware JE, Snow KK, Kosinski M. SF-36Òhealth survey: manual and
interpretation guide. Lincoln (RI): QualityMetric Inc; 2000.
15. Daly PB, Evans JH, Kobayashi RH, Kobayashi AL, Ochs HD, Fischer
SH. Home-based immunoglobulin infusion therapy: quality of life and
patient health perceptions. Ann Allergy 1991;67:504-10.
16. Acquardo C, Jambon B, Ellis D, Marquis P. Language and translation
issues. In: Spilker B, editor. Quality of life and pharmacoeconomics in
clinical trials. 2nd ed. Philadelphia: Lippincott-Raven; 1996. p. 575-85.
17. Fairclough DL. Design and analysis of quality of life studies in clinical
trials. Interdisciplinary statistics. Boca Raton (FL): Chapman &
Hall/CRC; 2002.
18. Brown H, Prescott R. Applied mixed models in medicine. New York:
John Wiley & Sons Ltd; 1999.
19. Fayers PM, Machin D. Quality of life. Assessment, analysis and
interpretation. Chichester: John Wiley & Sons Ltd; 2000.
20. Andersson RT, Aaronson NK, Wilkin D. Critical review of the
international assessments of health-related quality of life. Qual Life
Res 1993;2:369-95.
21. Waniewski J, Gardulf A, Hammarstro¨ m L. Bioavailability of gamma-
globulin after subcutaneous infusions in patients with common variable
immunodeficiency. J Clin Immunol 1994;14:90-7.
22. Gustafson R, Hammarstro¨m L. Subcutaneous immunoglobulin replace-
ment therapy. Ellipse 2002;18:45-8.
23. Gardulf A, Bjo¨ rvell H, Andersen V, Bjo¨ rkander J, Ericson D, Frøland S,
et al. Lifelong treatment with gammaglobulin to patients with primary
antibody deficiencies: the patients’ experiences of subcutaneous self-
infusions and home therapy. J Adv Nurs 1995;21:917-27.
24. Editorial. Hypogammaglobulinemia, fifty years later. Clin Immunol
2002;104:201-3.
25. Gardulf A, Mo¨ ller G, Jonsson E. A comparison of the patient-borne costs
of therapy with gammaglobulin given at the hospital or at home. Int J
Technol Assess Health Care 1995;11:345-53.
26. Note for guidance on the clinical investigation of human normal immuno-
globulin for intravenous administration (IVIg) (CPMP/BPWG/388/95 rev. 1).
The European Agency for the Evaluation of Medical Products; Human
Medicines Evaluation Unit. Committee for Proprietary Medicinal Products,
1999.
27. Note for guidance on the clinical investigation of human normal immuno-
globulin for subcutaneous and intramuscular use (CPMP/BPWG/283/00). The
European Agency for the Evaluation of Medical Products; Human Medicines
Evaluation Unit. Committee for Proprietary Medicinal Products, 2002
(operation date 2003).
28. Brennan V, Chapel HM. UK register of patients on home intravenous
immunoglobulin therapy. Immunodeficiency 1993;4:79-80.
29. Henderson K. Training and support to enable home therapy immuno-
globulin therapy. Nurs Times 2003;99:28-31.
J ALLERGY CLIN IMMUNOL
OCTOBER 2004
942 Gardulf et al
Basic and clinical immunology