Expert Review of Clinical Immunology

ISSN: 1744-666X (Print) 1744-8409 (Online) Journal homepage: http://www.tandfonline.com/loi/ierm20

Factors affecting quality of life in patients with

systemic lupus erythematosus: important
considerations and potential interventions

Claudia Elera-Fitzcarrald, Alejandro Fuentes, Luis Alonso González, Paula

Burgos, Graciela S. Alarcón & Manuel Ugarte-Gil

To cite this article: Claudia Elera-Fitzcarrald, Alejandro Fuentes, Luis Alonso González, Paula
Burgos, Graciela S. Alarcón & Manuel Ugarte-Gil (2018): Factors affecting quality of life in patients
with systemic lupus erythematosus: important considerations and potential interventions, Expert
Review of Clinical Immunology, DOI: 10.1080/1744666X.2018.1529566

To link to this article: https://doi.org/10.1080/1744666X.2018.1529566

Accepted author version posted online: 28

Sep 2018.

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Publisher: Taylor & Francis

Journal: Expert Review of Clinical Immunology

DOI: 10.1080/1744666X.2018.1529566
Article Type: Review

Factors affecting quality of life in patients with systemic lupus erythematosus:

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important considerations and potential interventions

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Claudia Elera-Fitzcarrald*¹,², Alejandro Fuentes*³, Luis Alonso González⁴, Paula
Burgos³, Graciela S. Alarcón⁵,⁶, Manuel Ugarte-Gil¹,²

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*Contributed equally. ¹Hospital Guillermo Almenara Irigoyen, EsSalud, Lima, Perú;
²Universidad Científica del Sur, Lima, Perú; ³Departamento de Inmunología Clínica y
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Reumatología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago,
Chile; ⁴Division of Rheumatology, Department of Internal Medicine, School of Medicine,
Universidad de Antioquia, Medellín, Colombia; ⁵The University of Alabama at
Birmingham, Birmingham, Alabama, USA; ⁶Universidad Peruana Cayetano Heredia,
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Lima, Perú.
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Corresponding author:
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Manuel F. Ugarte-Gil

Address correspondence to Manuel F. Ugarte-Gil, MD, Rheumatology Department.

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Hospital Guillermo Almenara Irigoyen. EsSalud. Lima-Perú.

Address: Av. Grau 800. La Victoria. Lima 13. Lima-Perú

Fax: +5113237298

E-mail: manuel_ugarte@yahoo.com
Abstract
Introduction: Patients with systemic lupus erythematosus (SLE) have a better survival
than decades ago; nevertheless, they still experience a low health-related (HR) quality of
life (QoL).
Areas covered: After defining QoL and HRQoL we review the need to assess it, its
elements, how to measure it, its predictors and its impact and potential interventions to
improve it.

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Expert commentary: Physicians assessments of disease activity and damage do not

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capture the patients’ perspective of their health, and these differences could lead to
nonadherence to therapy. Based on that, a comprehensive evaluation of SLE should

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include the assessment of HRQoL or the sum of the physical, psychological and social
perception of wellbeing, influenced by the patient’s illness. The most consistent

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predictors of low HRQoL are older age, poverty, lower educational level, behavioral
issues, some clinical manifestations and comorbidities. HRQoL impacts negatively on
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dealing with stress, intimal relationship, home and job-related activities and treatment
adherence. At the present, there are no successful specific therapeutic strategies aimed
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at improving it.

Key Words: Systemic lupus erythematosus, health-related quality of life,

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Introduction
Over the last few decades diagnostic and therapeutic advances have improved systemic
lupus erythematosus (SLE) patients’ life expectancy [1, 2] . However, with improved
survival new comorbidities, associated with the disease or with treatments received,
have emerged [3] leading to significant reductions in these patients’ health-related (HR)
quality of life (QoL) [4].

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The purpose of this review is to examine the following QoL-related topics in SLE:

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1. Definitions: QoL and HRQoL
2. The need to assess HRQoL

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3. HRQoL’s elements
4. Measuring HRQoL

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5. HRQoL’s predictors
6. HRQoL’s impact
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7. HRQoL’s interventions
8. HRQoL in childhood-onset SLE
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1. Definitions of QoL and HRQoL

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The World Health Organization (WHO) defines QoL as “individuals perception of their
position in life in the context of the culture and value systems in which they live and in
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relation to their goals, expectations, standards and concerns” [5]. It is a broad concept
affected by the individual's physical health, psychological state, personal beliefs, social
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relationships and their relationship with the environment [5]. In clinical medicine,
HRQoL is used as a multidomain concept indicating the overall impact a disease and its
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treatment have on the individual´s ability to function and their perceived well-being in
the physical, mental and social life domains [6].

2. The Need to Assess HRQoL in SLE

SLE patients experience events related to disease activity, irreversible damage, and
medications’ side effects which may negatively impact on their HRQoL and eventually
may result in disability (25%-57%) [7]. Thus, their evaluation should include disease
activity, damage and HRQoL [4].

HRQoL in SLE is lower than in the general population and in patients with other
common chronic diseases [4, 8, 9] and comparable to that of other severe medical
illnesses, such as the acquired immunodeficiency syndrome (AIDS), Sjögren´s syndrome
and rheumatoid arthritis; however, it is less impaired than in fibromyalgia [4].

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The Outcome Measures in Rheumatology Clinical Trials (OMERACT) recommended five
core domains to be evaluated in SLE clinical studies being them randomized controlled

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trials (RCT) or longitudinal observational studies, namely disease activity, damage,
HRQoL, adverse events and economic impact [10]. Similarly, the European League
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Against Rheumatism (EULAR) recommends assessing HRQoL at each clinic visit to
determine the burden SLE exerts on patients [11]. This recommendation reflects the
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fact that HRQoL, by and large, correlates poorly with disease activity and damage
accrual (vide infra) (Table 1) [10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,
27, 28, 29]. In fact, these three measures reflect different domains impacted by lupus,
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and all should be assessed to obtain a complete clinical picture; this provides additional
discriminatory power when assessing new therapies [10, 13]. These measures may be
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independent of each other; for example, SLE patients with fibromyalgia may have no
active disease or accrued any damage, yet, they may have poorer HRQoL than SLE
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patients without fibromyalgia [18, 30]. Furthermore, therapeutic interventions may

improve disease activity but may have limited to no impact on the patient’s HRQoL
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which tends to be stable over time [14]. In contrast, disease activity may change rapidly,
especially during flares or in patients with a relapsing-remitting pattern while organ
damage gradually accumulates over time [30, 31].

In addition, physicians and patients perceptions of SLE activity and overall health status
differ [4, 13], suggesting again that HRQoL should be assessed regularly. Physicians’
focus on alleviating disease activity and preventing damage as their primary
therapeutic goal without considering the patients’ perspective of their disease being
that in terms of fatigue and/or other patient-reported outcome (PROs); this may result
on patients’ poor adherence to treatment (s) and a dislocated communication with their
physicians [7, 31]. In fact, it has been shown that HRQoL is a determinant of medication
adherence, especially in patients who are depressed. Difficulties with adherence have
been found to be significantly associated with high-cost service utilization, specifically
with emergency departments’ visits [32, 33, 34]. Thus, it is important to recognize

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HRQOL as an independent health outcome that should be measured and targeted for

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improvement. To achieve this, factors affecting these patients’ HRQoL need to be
identified, and interventions to modify them implemented.

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3. Elements of HRQoL an
The effect of a disease on the patients’ perception of their physical, psychological, and
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social functioning constitutes HRQoL. Additionally, HRQoL reflects the extent to which
hopes and expectations are matched by experience [35], the patients’ perceptions of
their position in life considering the context of the culture and value systems where
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they live, the appraisal of one’s current state against some ideal [36] and things that
individuals regard as important [37].
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WHO has proposed a tool to measure all six HRQoL domains which in turn have specific
elements: physical (pain, discomfort, energy and fatigue, sleep and rest); psychological
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(positive feelings, thinking, learning, memory, concentration, self-esteem, body image

and appearance, and negative feelings); level of independence (mobility, daily
activities, dependence on accompaniment or treatment and work capacity); social
(personal relationships, social support, and sexual activity); environmental (physical
safety and security: the home environment, financial, health care, social care,
recreation/rest, physical environment, and transport); and spirituality (spirituality,
religion, personal beliefs) [38].
a. Physical Functioning

Fitness and an adequate physical activity level exert a positive impact on the patients’
HRQoL; furthermore, low physical activity levels have a negative impact as they
predispose to cardiovascular disease, osteoporosis, obesity, fatigue and sleep disorders.
[39]. Pain also limits the patients’ ability to perform from simple to complex activities.
Body image concerns SLE patients as they experience weight gain and skin changes
which negatively impact their self-esteem [40]. Fatigue prevents adequate physical

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functioning and is influenced by the disease, and by psychosocial and personal factors

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[41] including disease activity, sleep disorders, depression, anxiety, despondency, pain,

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emotional disorders, obesity, reduced physical activity, comorbidities, vitamin D
deficiency and treatments used [42].

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b. Mental Functioning
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Around 60% SLE patients suffer from an emotional disorder being the most commonly
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observed sadness, depression, fear, anxiety, guilt and anger [40]. Anxiety was reported
by 70.7%, mood disorders by 61.3% and depression by 50.3% in a study of 225
European patients in which 194 completed the questionnaires [43]. Mental functioning
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is influenced by patient's concerns; the two major ones, as reported by Golder et al, are
a reduced ability to perform activities of daily living (ADL) and a reduced ability to
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perform physical activities due to pain or fatigue; these concerns were reported by
62.7% and 60.6% of 84 patients studied, respectively [44].
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c. Social Functioning

QoL is influenced by employment, housing, public services access, communications,

urbanization, crime, environmental pollution and other factors that influence human
development [45]. In addition, having family support makes possible for patients to
avoid excessive burden; having a partner may improve the patient's HRQoL but whether
this is because of the partner's support or because people with lower HRQoL cannot
establish fruitful relationships [46], is unclear. As for employment, high disease activity,
fatigue and pain prevent patients from continuing their job-related activities. In
addition, patients are also concerned about their illness’ costs including out-of-pocket
and healthcare insurance expenses [47].

4. How to measure HRQoL in SLE

HRQoL can be assessed with generic and disease-specific questionnaires [6]. Generic

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QoL questionnaires are used in the general population’s healthy and diseased
individuals. Their advantage is that the scores obtained in different populations and

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conditions can be compared allowing the measurement of disease burden and health
resources allocation. In addition, many generic questionnaires have undergone

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extensive validation and have been adapted to multiple languages and cultures.
However, a disadvantage to use them alone is that they may inadequately ascertain
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QoLs dimensions specific to lupus patients, such as physical appearance and fertility.
Furthermore, generic instruments may not be sensitive enough to capture the
fluctuations in health status observed in SLE patients [6, 31, 33, 39, 48, 49]. In contrast,
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disease-specific questionnaires tend to be more sensitive to change and are more

appropriate to evaluate specific therapeutic interventions in clinical trials. Both types
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have been used in patients with lupus [6, 33, 39, 48].
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When assessing HRQoL, it is important to be aware of the instruments’ psychometric

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properties [48] which are categorized into three domains: validity, reliability and
responsiveness. Validity includes evaluation of content (convergent or divergent),
construct and concurrent validity. Content validity ensures that the measure is sensible,
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pertinent and comprehensively covers all aspects of the condition assessed; convergent
validity is adequate if there are high positive correlations between scales whereas
divergent or discriminant validity if correlations are low negative. Construct validity
assesses the robustness of the questionnaire and determines its subscales. Concurrent
(criterion) validity refers to the comparison with the true value or gold standard.
Reliability assesses the reproducibility and consistency of an instrument. Internal
reliability or internal consistency measures the extent to which items within a subscale
are conceptually related whereas test-retest reliability measures the questionnaire’s
stability. Responsiveness or sensitivity to change, is the scale’s ability to detect changes
within the same patient over time. Floor and ceiling effects refer to the percentages of
participants scoring the minimum (floor) and maximum (ceiling) possible scores for
HRQoL measures [50].

The characteristics of various generic and SLE-specific HRQoL tools are summarized in

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Table 2.

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a. Generic measures

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Several generic questionnaires have been used to assess HRQoL in SLE, being the most
commonly used the Medical Outcomes Study Short Form-36 (MOS SF-36 or SF-36) [16,
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51], the EuroQoL-5 Dimensions (EQ-5D) [52], the Short Form-6D (SF-6D) [53], the
Patient-Reported Outcomes Measurement Information System (PROMIS) [57], the
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WHOQOL-BREF [58], the Short Form-20 (SF-20) [59], the Nottingham Health Profile
(NHP) [60] and the Sickness Impact Profile (SIP) [61].
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SF-36
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It is a 36-item self-report questionnaire that has been applied in a variety of conditions

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and chronic diseases [6, 8, 15, 16, 19, 31, 62, 63, 64, 65, 66] and is the most frequently
used. It comprises eight domains or subscales of perceived health [physical functioning,
role physical, social functioning, bodily pain, mental health, role emotional, vitality
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(energy level and fatigue) and general health perceptions] which are summarized into
two components: the physical and the mental component summary scores: PCS and
MCS, respectively [51]. However, evaluating all domains along with the summary scores
is desirable to capture changes in all domains. Both summary measures are
standardized and can be compared between and within populations. This questionnaire
is scored from 0 (the worst) to 100 (the best).
The SF-36 is a valid and reliable instrument for SLE patients [8, 16, 51]. However, some
concerns about its sensitivity in capturing changes in health status, especially over long
time periods, have emerged. In longitudinal studies, the SF-36 is not sensitive to change
when evaluated it annually [31, 64] as it assesses only the preceding month; thus, the
longitudinal assessment of QoL cannot be considered comprehensive given lupus
fluctuating course and the fact that it does not capture the patient’s full experience
throughout the entire year [31, 64]. For example, in established patients from the

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University of Toronto Lupus Clinic, little changes in HRQoL were found over an 8-year

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period in patients completing the SF-36 yearly; furthermore, these changes were not
affected by disease activity, steroid dose or damage accumulated during the interval but

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were affected by the presence of fibromyalgia [31]. In another study from the
multicenter Systemic Lupus International Collaborating Clinics (SLICC) inception

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cohort, all eight domains and the two summary scores improved in the first two years
and remained stable over the ensuing three; these data suggest that the SF-36 may be a
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sensitive outcome measure in early SLE but not otherwise [66]. However, when the SF-
36 was administered monthly over six to 12 months, its scores changed in parallel with
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clinically significant changes in disease activity in patients from The Montreal General
Hospital [49] and the University of Toronto Lupus Clinics [52] [19, 65]. Thus, it may be
appropriate to use the SF-36 to assess HRQoL in short-term follow-up studies or early in
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the patients’ disease course. Finally, the SF-36 is frequently used as a legacy instrument
to validate other tools, including SLE-specific HRQoL instruments [20, 24, 55, 56].
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EQ-5D

The EQ-5D is a simple generic instrument that assesses five dimensions of health status
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[mobility, self-care, usual activities (work, study, housework, family o leisure activities),
pain/discomfort, and anxiety/depression]; each dimension has three levels of response:
none, some-to-moderate, or extreme problems. The results are reported as a summary
score from 0 (death or health worse than death) to 1.0 (best imaginable health). In
addition, patients rate their current health on a 20-cm visual analog scale (EQ-5D VAS)
ranging from 0 (worst imaginable health) to 100 (best imaginable health) [52]. This
instrument offers the advantage of allowing economic evaluation of health care
interventions in addition to measuring HRQoL [67].

EQ-5D exhibited satisfactory psychometric properties when assessed in a US SLE

multiethnic patient population supporting the notion that it is a valid and reliable SLE
HRQoL measure and highlighting the discrepancies between HRQoL and disease activity
and damage. Moreover, related domains on the EQ-5D and SF-36 are strongly correlated

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(e.g., mobility and physical functioning, anxiety/depression and mental health,
pain/discomfort and bodily pain), whereas unrelated domains showed weak to

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moderate correlations (e.g. self-care and social functioning, usual activities and general
health perceptions) [21].

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Since the EQ-5D provides less information than multidimensional profile measures such
as the SF-36, this measure tends to be brief and simple and amenable to self-
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administration. The EQ-5D contains only five items plus a VAS and takes two minutes to
complete. Furthermore, a single summary HRQoL score is simpler to understand and to
follow longitudinally than multiple measures and can be used to convey the burden of
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illness relative to other conditions and to make resource allocation decisions. The EQ-
5D also provides preference-based scores that can be used to facilitate the calculation of
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quality-adjusted life-years to evaluate treatments’ comparative effectiveness [21]. The

EQ-5D has been translated into most major languages and is widely used to evaluate
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many conditions, including SLE [52, 68, 69].

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SF-6D

The SF-6D is a 6-dimensional preference-based scoring system derived from the SF-36
using an standard gamble methodology-based algorithm [53]; the SF-36’s eight
dimensions were reduced to six by excluding the general health dimension and
combining the physical and mental role limitations’ dimensions into one. The final index
includes items from the other six dimensions: three from physical functioning, two from
role limitations and pain and one each from social functioning, mental health and
vitality; this index provides a single numeric value ranging from 0.296 (worst possible
health, worse than being dead) to 1.0 (perfect health) which may be easier to grasp for
clinicians and researchers than the different SF-36 scales and summary measures.
Furthermore, this measure also tends to be brief and easy for the patient to self-
administer it [21, 70]. The SF-6D was originally conceived for economic evaluations as a
utility measure but it is used to accurately assess overall health status in SLE patients
[21, 70, 71] and other conditions [72, 73, 74].

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Like the EQ-5D, the SF-6D has been found to be a valid and reliable HRQoL measure in a

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US multiethnic SLE population[21]. The EQ-5D and the SF-6D summary scores correlate
strongly; they also correlate with most SF-36 domains. However, the SF-6D correlates

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poorly with measures of disease activity and damage as noted by Aggarwal et al [21] but
not by Fernández et al who found it to predict damage accrual in the LUMINA (Lupus in
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MInorities, NAture versus nurture) cohort’ patients [70].
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PROMIS
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The US National Institutes of Health (NIH) initiative PROMIS was charged with
developing health status’ self-report measures for adult and pediatric individuals across
a range of domains (e.g., fatigue, pain, sleep disturbance, physical function, anxiety,
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depression, satisfaction with social role) and health conditions [57]. Being generic,
PROMIS allows comparison across disease and non-disease groups. PROMIS domains
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can be selected to suit a specific health condition, with questions related to selected
domains administered via computerized adaptive tests (CATs) or as short forms
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without using CATs, e.g., PROMIS10 [26, 27, 54].

PROMIS utilizes item-response theory and CATs, which select the informative questions
from a domain item-bank based on individuals’ previous responses. CATs include
physical function, mobility, pain behavior, pain interference, ability to participate in
social roles, satisfaction with social roles, fatigue, sleep disturbances, applied cognition-
abilities, anger, anxiety and depression. There are usually 4-12 items per CAT with a
high level of measurement precision. This allows the use of fewer questions per domain
to obtain precise measurements than traditional short-form questionnaires, reducing
responders burden while enhancing the ability to capture changes over time at the
individual level [26, 54].

PROMIS10 is a 10-item PRO instrument measuring physical and mental health domains
in a wide variety of chronic diseases. The PROMIS Global-health SF consists of seven

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questions asking subjects to rate “in general” their physical, emotional, and social
health, and three questions related specifically to emotional health, fatigue and pain in

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the seven preceding days [27]. These 10 questions have largely been adapted from
other “legacy” instruments including the SF-36 [51] and the EQ-5D [52]. PROMIS10 is

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scored into global physical and mental health components using a T score metric,
allowing for comparisons with the general population. For the general US population,
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the mean PROMIS10 T score is 50 with an SD of 10; higher PROMIS T scores reflect
more of the trait being measured; higher global physical and mental health component
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scores indicate better health. PROMIS CAT is scored through the Assessment Center
using the T score metric which is equally interpreted [27].
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The feasibility, validity, reliability and, test-retest reliability of PROMIS CATs [26, 54]
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and PROMIS10 [27] were demonstrated in 238 ambulatory US SLE patients when
compared to existing “legacy” instruments. PROMIS10 correlates strongly with both,
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SF-36 and Lupus QoL; PROMIS10 physical health scores strongly correlate with the
physical function, pain, and social health domains of PROMIS CAT, SF-36, and LupusQoL,
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while mental health scores strongly correlate with PROMIS depression CAT, SF-36, and
the LupusQoL’s mental health domains. Similarly, PROMIS CAT showed strong
correlations with the SF-36 and the LupusQoL across analogous domains. PROMIS
physical function and mobility CAT correlate strongly with the SF-36’s (PCS) and
LupusQoL’s physical function. Similarly, for the mental domain, PROMIS anxiety, and
depression CATs correlate strongly with the LupusQoL emotional health domain, and
moderately with the SF-36’s mental health–related scales. PROMIS social function CAT
also correlates moderately to strongly with the SF-36 and LupusQoL corresponding
domains[26]. Test-retest reliability for PROMIS10 and PROMIS CATs’ physical and
mental health scores are high. Both correlate poorly with disease activity and damage
[26, 27]. Finally, PROMIS pediatric short forms have been evaluated in children with SLE
demonstrating construct validity and responsiveness; this is an advantage of PROMIS
over legacy instruments which are not tailored to children. Using PROMIS may allow the
assessment of pediatric patients into their adulthood [75]. Furthermore, PROMIS10
requires less than two minutes to complete, which is less than the time required for the

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Lupus QoL (4.6 minutes) or the SF-36 (5 minutes). PROMIS10 is available in many

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different languages [27].

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b. SLE-Specific Measures
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Several SLE-specific tools have been designed to ascertain HRQoL. They include the
Lupus QoL or LupusQoL [55], the SLE-Specific QoL Questionnaire or SLEQOL [20], the
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SLE QoL Questionnaire (L-QoL) [56] and the Lupus PRO [24]. All these measures have
gone through validation tests (vide infra).
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LupusQoL
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This is the most widely studied SLE-specific HRQoL measure, developed and validated
in SLE adults from the United Kingdom (UK) [55]. Since then, it has been validated in a
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sample of US patients [76]. Likewise, a Spanish version has been adapted and validated
[22]. The LupusQoL has also been translated into 77 languages for use in 51 countries
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[77]; it consists of 34 items derived from SLE patients and grouped into eighth domains:
physical health, emotional health, body image, pain, planning, fatigue, intimate
relationships and burden to others. The questions refer to the patient's experience over
the preceding four weeks; responses are given on a 5-point Likert scale (0-4, where 0
means all the time and 4 never). A summary LupusQoL score is reported on a scale of 0
to 100, with higher values indicating a better HRQoL, 0 representing the worst HRQoL
and 100 the best HRQoL. As for the respondent burden, the time to complete is less than
10 minutes [55].
In the original UK sample, LupusQoL demonstrated good acceptability, reliability, and
test-retest reliability. Concurrent validity was assessed by comparing its domain scores
with comparable SF-36 domains’ scores [55]. Similar results were obtained in the US
and Spanish validation studies [22, 76]. The LupusQoL has discriminant validity (the
ability of the instrument to differentiate between patients of varied disease severity)
functioning relatively independently as an SLE outcome measure as demonstrated in

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studies from the UK, US and Spain. Weak to no correlations were found between Lupus

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QoL and disease activity and damage in these studies [22, 55, 76]. For example, in the

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original UK study, patients with more active disease, as assessed by the British Isles
Lupus Assessment Group (BILAG) generally reported poorer HRQoL across all domains

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except fatigue whereas some domains (emotional health, body image, and fatigue) could
not discriminate between patients with or without damage (using the Systemic Lupus
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International Collaborating Clinics/American College of Rheumatology Damage Index or
SDI) [55].
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SLEQOL
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The SLEQOL was originally developed and validated in English-speaking Singapore SLE
patients to assess their HRQoL [20]. It includes 40 items grouped into six domains:
physical functioning, activities, symptoms, treatment, mood, and self-image. These items
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were generated by rheumatologists and nurse practitioners, not by patients. The

questions pertain to the patient’s experience over the previous week and are answered
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with a 7-point Likert scale. The total score is the sum of all responses across all
domains, ranging from 40 to 280, with higher values corresponding to worse QoL. As for
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the respondent burden, the time to complete this questionnaire is less than five
minutes.

Regarding its psychometric properties, the SLEQOL has good test–retest reliability but
poor correlation with the SF-36, lupus activity or damage indices; however, it is more
responsive to change than the SF-36. The poor correlation between the SF-36 and the
SLEQOL is due to non-overlapping QoL domains. The SF-36 inquiries about QoL in
general while the SLEQOL is specific about areas of concern to lupus patients. In
addition, the SLEQOL has significant floor effects, such that respondents reported good
QoL beyond what can be measured by the instrument while the SF-36 had fewer floor
but more ceiling effects (poor QoL). Thus, coadministration of the SLEQOL with a
generic HRQoL instrument such as the SF-36, may be required to address these
limitations [20]. Finally, this instrument has good discriminant validity as it functions
independently from measures of disease activity and damage [20, 77].

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L-QoL

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The L-QoL is a SLE-specific HRQoL measure developed using a needs-based QoL model,

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which postulates that life gains in terms of its quality result from the ability and capacity
of individuals to satisfy their needs. Its validation has been assessed in a UK SLE sample
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and, recently, in a Turkish population [25, 56]. L-QoL comprises 25 items that assess the
overall effects of SLE and its treatment on QoL. This tool was derived from qualitative
interviews with SLE patients exploring the impact of their disease. Each question is
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answered as true/non-true; the scores range from 0–25, with higher scores indicating
worse QoL. The questionnaire is easy to complete taking less than five minutes. The L-
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QoL has excellent test–retest reliability and internal consistency indicating its suitability
for use with individual patients. Construct validity, assessed only against patient-
reported disease activity and severity, was also found to be adequate; those with higher
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perceived disease activity, higher perceived disease severity, and fair/poor ratings of
their general health, had statistically significantly L-QoL scores [56].
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Unlike other instruments that measure HRQoL using multidimensional constructs that
yield a profile of scores, the L-QoL provides a single unidimensional score representing
the overall impact of SLE and its treatment [56, 77].

Lupus PRO
The LupusPRO tool is based on the feedback provided by ethnically heterogeneous US
patients of both genders. It has 44 items that cover both, HR and non-HRQoL domains
and is presented in a gender-neutral language. HRQoL domains include: lupus
symptoms, physical health (physical function, role physical), pain–vitality, emotional
health (emotional function and role emotional), body image, cognition, procreation, and
lupus medications. Non-HRQoL domains include available social support and coping,
desires and goals, and satisfaction with medical care. Respondents indicate their

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experience in the previous four weeks on a 5-item response scale; domain scores range

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from 0 to 100, where higher scores indicate better health [24].

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When applied to the initial validation cohort, the LupusPRO demonstrated good internal

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consistency, reliability, and test-retest reliability for all its domains, except for the lupus
medication domain. Corresponding domains of the LupusPRO and the SF-36 correlate
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strongly, supporting its concurrent validity. Criterion validity is suggested by strong
correlations of the LupusPRO domains with disease activity as measured by the BILAG,
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the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus
Erythematosus Disease Activity Index (SELENA-SLEDAI), and the Lupus Foundation of
America flare definition but correlations with disease damage were moderate [24].
ed

Finally, the LupusPRO has been translated and validated into various languages
confirming its use across several cultures and diverse SLE patient populations [28, 78,
pt

79, 80, 81, 82, 83].

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5. Predictors of HRQoL

a. Sociodemographic

It has been consistently shown that older age, poverty and lower education levels are
predictors of a lower QoL [15, 84, 85, 86]. As to race/ethnicity, Caucasians have been
shown to have a poorer physical function domain of the SF-36 compared to non-
Caucasians in a Canadian study of 146 SLE patients[31]; furthermore, lower PCS scores
were seen in Caucasians versus Asians in a multinational Asia-Pacific Lupus
Collaboration study of 1422 SLE patients [87]. In the multiethnic US LUMINA cohort,
African-Americans exhibited diminished MCS and some related SF-36 subscales (social
functioning and role emotional) in multivariable analysis [15]; nevertheless, the authors
concluded that ethnicity was not a consistent predictor of HRQoL in SLE [15]. A worse
perception of their neighborhood has also been associated with poorer HRQoL [88]. In

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addition, psychological and behavioral elements such as helplessness, inadequate social

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support and coping with illness mechanisms, are predictors of a lower QoL [4, 15, 48].
Also, patients with SLE have a lower satisfaction with life in general, a construct that has

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moderate to strong correlation with HRQoL[84].

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b. SLE-related manifestations
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A low baseline QoL is an important predictor of a poor subsequent QoL [15, 46]. In
terms of the relationship between disease activity and QoL, there are variable results, as
M
already noted. [15, 30, 46, 89, 90]. Some possible explanations for this could be the use
of nonspecific scales to assess HRQoL [84] and of different tools to ascertain disease
ed

activity [91], the heterogeneity of lupus [84], and the role of socio-demographic (age,
educational level) and behavioral (coping with illness) factors that modulate disease
activity [92]. On the other hand, the use of the LupusQoL has shown a more consistent
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inverse correlation between disease activity and QoL [93, 94, 95, 96, 97]. A recent
historical Chinese study of 453 SLE patients showed that subjects on remission for five
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or more years had better scores on SF-36 and the LupusPRO’ s HR’s domains. [91]. Also
a lupus low disease activity state (LDAS) as recently defined [87] has been associated
Ac

with a better HRQoL in the aforementioned multinational Asian study of 1422 patients
[86]. Moreover in a study from Perú, the use of immunosuppressants, as a probable
surrogate of higher disease activity, associated with worse scores in some of the
LupusQoL domains such as physical health, pain, planning, burden to others, emotional
health and body image [96]; this could also be due to the impact of medications’ adverse
events on HRQoL.
There is a complex relationship between organ damage and HRQoL with an initial
decrease in SF-36 when there are sudden increases in the SDI and then a change to the
levels observed in patients without damage progression. A possible explanation is that
patients with lupus have been shown to develop adaptability to chronic damage [98].
Time from diagnosis of SLE is not a clear predictor of QoL [15, 30, 64].

The presence and severity of SLE cutaneous manifestations (CM-SLE) as

t
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photosensitivity, diffuse alopecia or cutaneous lupus are important factors associated
with an impaired HRQoL, especially in the emotional domain of the Skindex-29 (a

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generic QoL dermatologic scale). Also, the impact of CM-SLE is worse in lupus
compared to other skin diseases such as acne, rosacea or psoriasis [99]. A Japanese trial

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of 54 patients with SLE and cutaneous lupus (by histopathology) showed an improved
Skindex-29 scale after treatment [100].
an
M
Several studies have shown that patients with SLE and neuropsychiatric (NP) symptoms
(SLE or not SLE-related) are prone to a diminished HRQoL [101, 102, 103]. Moreover, it
seems that inflammatory NPSLE manifestations have a better outcome in HRQoL than
ed

ischemic NPSLE or non NPSLE events, as a recent prospective Dutch trial of 131 SLE
patients has reported [104].
pt
ce

SLE patients with lupus nephritis (LN) tend to have poor HRQoL, particularly on the SF-
36’s physical domain and with the LupusPRO’s lupus medications, procreation,
Ac

emotional health, body image and desires-goals domains in population with active LN
[105, 106].

Musculoskeletal manifestations are very common in SLE [107] and they have been
shown to correspond with declines in the SF-36 [15, 108].
c. Comorbidities

Fibromyalgia, occurring in 9.5% to 35.7% of lupus patients, is an independent and

important HRQoL predictor [4, 15, 30, 64, 93, 109, 110, 111]. Likewise, SLE patients
with anxiety and depression present a low HRQoL [112, 113, 114]; that is particular the
case with depression [93, 112, 115, 116, 117, 118]. Both are relatively frequent in SLE
patients with prevalence rates of 24% and 37%,respectively. Interestingly, depression
has been related to disease activity levels as assessed by the Systemic Lupus Activity

t
Questionnaire (SLAQ) [116] or by the Patient’s Global Assessment (PGA) [118]; that has

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not been the case with the SLEDAI. Also, patients with depression and SLE experience

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greater work disability [113]. Finally, patients with the metabolic syndrome (MetS)
have been found to have lower levels of functioning (PCS and MCS) than those without it

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in a cross-sectional study encompassing 100 Italian SLE patients [119].
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6. Impact of HRQoL
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HRQoL affects several aspects of the patients’ lives including how to deal with stress,
ed

their intimal relationships, their work- and home-related activities and their adherence
to treatment. They, oftentimes, experience variable degrees of physical and mental
limitations [7]; they can face these limitations by intentionally minimizing their impact
pt

(coping) or maximizing it (catastrophizing) [120]. A poor mental component of HRQoL

is associated with a higher catastrophizing score [121], which may turn to be a two-way
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interaction: poorer HRQoL increases catastrophizing, which worsens pain and

depression reducing further the patient’s HRQoL. As to intimal relationships, women
Ac

with SLE present a lower sexual function than healthy controls [122] whereas a better
HRQoL is associated with a better sexual function [123].

Poorer HRQoL, particularly its physical component, is associated with work disability
[9, 124]; the relationship between HRQoL and work disability is bidirectional, better
HRQoL allows the patient to work; in turn, work makes the patients feel better. Poor
HRQoL is also associated with work productivity impairment, activity impairment [125,
126] and ADL’s difficulties; oftentimes, patients may need help from family and/or
friends [127].

Poor treatment adherence is an important cause of treatment failure in patients with

chronic diseases; however, self-reported questionnaires to measure it are not reliable.
In the case of antimalarials, blood monitoring can be done, although this is not a routine
practice. In fact, a better HRQoL is a predictor of non-adherence to them, particularly in

t
ip
nonactive patients [128]; as patients feel better, they may abandon their treatment in
fear of their side effects, one of the main predictors of poor treatment adherence in

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patients with different disorders, SLE included [129]. The interaction of factors related
to HRQoL is shown in Figure 1.

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an
7. Potential interventions
M

a. Pharmacologic
ed

No specific treatment regimen to improve patients’ HRQoL per se does exist; physicians
may assume that HRQoL will improve as patients are treated for their lupus. Scanty data
are however available. For example, in a RCT of 47 US patients who were first time
pt

cyclophosphamide (CYC) users (29%, 45% and 26% of them had LN, NPSLE or other
organs compromise, respectively), a high dose of CYC (50 mg /kg for 4 days) regimen
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had better results in the general health and social functioning SF-36’s domains at six
months and for the physical role at eighteen months, compared to a monthly CYC
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regimen of 750 mg/m² body surface for six months [131]. Interestingly, in the same
study, both groups presented similar QoL at two and a half years. [131]. In the Euro-
lupus vs the NIH protocol trial, 16 LN patients per group were studied; no differences in
HRQoL between these groups were found [132]. Finally, in a LN study from Hong Kong,
patients treated with mycophenolate mofetil plus prednisone had better HRQoL than
those treated with oral CYC and prednisone[133].
As to lupus overall, in a blinded RCT using methotrexate as a steroid-sparing agent, the
MCS score improved by 2.78 points (96% CI, 0.13-5.44, p = 0.034) in the active
treatment group [134]. In another open randomized study, which compared
azathioprine and cyclosporine as steroid-sparing agents in SLE, no differences in these
patients’ QoL was observed at baseline and 12 months later [135].

Despite the known effects of antimalarials (hydroxychloroquine, HCQ) in terms of

t
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improved survival and flares prevention [136], no improvement in HRQoL was
observed in French SLE patients in whom the association between HCQ blood levels and

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QoL was examined [137]; however, in a recent Peruvian study of 277 SLE patients,
better scores in some domains of the LupusQoL questionnaire (physical health, burden

us
to others and body image) were found in current and past antimalarial users [96].
an
As to B-cell-targeted therapy, in the BLISS 52 and 76 belimumab studies,
M
improvements in the SF-36’s PCS and MSC scores were observed at week 52 on the
active but not in the placebo groups; in addition, an improvement in fatigue was
observed from week eight on [138, 139]. Rituximab, has not been shown to result in any
ed

improvement in HRQoL (SF-36) as compared to placebo in patients with moderate to

severe SLE [140].
pt
ce

In terms of adrenocorticotropic hormone, in a single-center , open- labeled trial, the

subcutaneous use of 80 units for 10 days and an optional five day rescue period in
Ac

patients with moderate to severe SLE demonstrated a significant improvement in

LupusQoL at day 28 and reduced fatigue from day 14 on [141]. The use of a
dehydroepiandrosterone (DHEA) supplement for six months versus placebo, followed
by an open six months of DHEA treatment for all patients, demonstrated a better HRQoL
in 37 women with SLE treated with glucocorticoids in a double-blind RCT. While the
role emotional domain of the SF-36 improved in the DHEA group during the blinded
placebo-controlled period (until month six), the placebo group improved in the MCS
during the open phase of the study (months six to 12) [142].
b. Nonpharmacologic

A few interventions aimed at improving HRQoL have been tried. A randomized 5-month
control study comparing cognitive-behavioral therapy (CBT) and habitual therapy was
conducted in 45 SLE patients; the CBT group improved in their physical function,
vitality, general health perceptions, and mental health domains of SF-36 [143]. On the
other hand, it has also been observed that patients who establish a working alliance

t
ip
with their treating physicians have better QoL levels while having attachment anxiety
leads to a worse QoL[144].

cr
us
The beneficial effects of physical exercise in lupus patients’ HRQoL has been
demonstrated in several studies [145, 146, 147, 148]. Significant differences have been
an
seen in all HRQoL areas assessed with the SF-36 in a six-week follow-up study of
aerobic or isotonic exercise [146]. When comparing types of exercise, resistance
M
training (RT, n = 21) and cardiovascular training (CT, n = 21) in a 12- week follow-up
study, the CT group fared better than the RT or the untreated control groups (n=21) in
improving their HRQoL [145].
ed
pt

As to complementary or alternative medicine (CAM), 49.8% of patients used CAM in the

Lupus TRINATION Study Group (707 patients from Canada, US and UK) and they had
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lower scores of the SF-36 [149]. In developing countries, there is also a high use of these
therapies; for example, in a Mexican cross-sectional study of 92 patients, 53.6% used
Ac

CAM (herbal or food supplements and mind-body medicine) but that did not affect their
HRQoL [150].

With respect to acupuncture, a US pilot feasibility and safety trial of 24 patients who
continued their usual medical care, were randomized to ten sessions of acupuncture,
minimal needling or usual care alone; an improvement in fatigue and pain was observed
in the first two groups [151].
Mind-body medicine has been studied in a trial of 30 LN patients from Thailand; the
group that used the meditation program for six months, as instructed by an expert
Buddhist, had better SF-36 scores than the control group [152]. And in a recent Iranian
single blind RCT of 46 SLE patients, the group that performed eight sessions of
mindfulness-based cognitive therapy (MBCT) plus standard of care fair better at the
end of the intervention and six months afterwards than the standard of care group

t
[153] in MCS but not PCS scores [153].

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8. HRQoL in childhood-onset SLE

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Childhood onset SLE (cSLE) is a rare disease with an incidence ranging from 0.3-0.9 per
an
100 000 person-years and a prevalence of 1.89 to 25.7 per 100 000 children across the
world. It is predominantly observed in non-Caucasian and female children [154, 155,
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156]. Studies of patients with cSLE have demonstrated impaired HRQoL as compared to
healthy children [157, 158, 159].
ed

The Pediatric Quality of Life Generic Core Scale 4.0 (PedsQL-GC) which is a self-report
tool comprised of 23-items corresponding to four domains: physical, emotional, social
pt

and school function; this tool is used to evaluate HRQoL in children. There is also the
Pediatric Quality of Life Rheumatology Module 3.0 (PedsQL-RM), which is similar to the
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PedsQL-GC, but is relevant for children with rheumatic diseases; this tool has 22-items
across five domains which include: pain and hurt, daily activities, treatment, worry and
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communication; items are rated on a 5-point scale (0 = never to 4 = almost always), and
from the raw scores a summary score of 0 to 100 can be calculated, higher scores are
representative of better HRQoL [160]. Likewise, the Simple Measure of Impact of Lupus
Erythematosus in Youngsters (SMILEY) is a 26-item, cSLE specific, HRQoL questionnaire
that features four domains: Effect on self, Limitations, Social and Burden of SLE.
Responses are reported with a 5-faces scale. Each score ranges from 1 to 5 and the total
score is transformed to a 1 to 100 scale with higher values representative of better
HRQoL [161]. Moreover, the Child Health Questionnaire (CHQ-PF50) is parent proxy-
report of generic health status. The CHQ-PF50 is a profile measure of 50 questions that
measures 10 mental and physical domains, or subscales: physical functioning, bodily
pain, general health perceptions, role/social limitations-physical, role/social
limitations-emotional/behavioral, parent impact-time and parent impact-emotions, self-
esteem, mental health and general behavior. Each subscale score ranges from 0 to 100,
with higher scores representing better health status [160]. Other versions of CHQ are
CHQ-PF28[162] which is also to be used by the parents and the CHQ-CF87 and CHQ-

t
CF45 which are for children at least 10 years of age[163].

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In cSLE, disease activity and damage impact to a certain extent their HRQoL [157, 164].

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Groot et al, in a 111 cSLE patients with a median disease duration of 20 years, found
damage in 62%, predominantly in the musculoskeletal, neuropsychiatric and renal

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systems; furthermore, cerebrovascular accidents, renal transplants, replacement
arthroplasties and myocardial infarctions developed at young age in these patients. In
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this study, damage, high disease activity and changes in physical appearance were
associated with a reduced HRQoL [165]. On the other hand, Jones et al observed that
M
Pediatric Quality of Life (PedsQL) scores were lower in cSLE (n=60) than in healthy
children; a reduced PedsQL was highly correlated with greater levels of fatigue, pain,
anxiety and depressive symptoms [166].
ed

Adults with cSLE develop significant damage at young age and have impaired HRQoL
pt

without generally achieving drug free remission, impacting their future life.
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9. Conclusions
Ac

HRQoL is the sum of the physical, psychological and social perception influenced by the
individual's illness.

The most consistent predictors of low HRQoL in SLE are socio-demographic factors such
as older age, poverty and lower educational level. Other important factors are
behavioral issues, SLE clinical manifestations (skin, NP, renal and musculoskeletal) and
prevalent comorbidities (fibromyalgia and depression). When the SLE-specific
LupusQoL is used, activity and previous damage accrued are, by and large, associated
with worse HRQoL in patients with lupus but that is not the case, in general, when
generic instruments are used.

HRQoL impacts negatively on dealing with stress, intimal relationships, home and job-
related tasks and treatment adherence. There are no defined successful therapeutic
strategies aimed at improving HRQoL in these patients.

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10. Expert Commentary

us
Improved survival in SLE has not paralleled improvements in their HRQoL. Since lupus
affects a relatively young population, the clinical manifestations of the disease may have
far-reaching psychological and social consequences given these patients life expectancy.
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Physicians’ objective assessments of disease activity and damage do not capture, in
general, these patients’ health perspective. These discordant perspectives may result in
M
nonadherence to therapy which in turn is associated with high-cost service utilization.
Thus, a comprehensive evaluation of SLE also requires assessing these patients’ HRQoL,
ed

which can be accomplished by generic and disease-specific questionnaires, which

should have adequate psychometric properties. These questionnaires assess the
patient's perspective on how the disease impacts them on its three dimensions:
pt

physical, psychological and social. It is important to establish the ideal time required to
determine whether a given feature or characteristic is predictive of HRQoL in SLE. To
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this aim, the most specific SLE QoL questionnaires should be chosen for research
purposes. Addressing HRQoL’ associated factors may improve these patients overall
Ac

functioning and their adherence to treatment.

11. Five-year view

Most studies assessing HRQoL in SLE are cross-sectional; longitudinal studies are
required to better determine the factors predictive of HRQoL, as well to determine the
best instruments to detect changes (responsiveness) secondary to specific
interventions. Furthermore, most studies evaluating the negative impact of SLE on
HRQoL come from developed countries; studies from developing countries are needed
given the known negative impact that poor socioeconomic status has on patients´
HRQoL. Also, since most studies validating HRQoL instruments have been conducted in
ambulatory settings, whether they are applicable in the inpatient settings remains to be
defined.

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Several generic and disease-specific instruments have been validated to assess HRQoL
in SLE, but they have some limitations; for example, generic instruments lack some

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domains relevant to SLE patients whereas SLE-specific instruments include them (e.g.,
body image, fertility) but may have significant floor and ceilings effects. PROMIS

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instruments on the other hand, increase measurement precision and reduce responder
burden relative to traditional instruments as they use item response theory and include
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CATs. Strategies aimed at improving HRQoL combined with a treat-to-target strategy
should result in better overall and patient-reported outcomes.
M

12. Key Issues

ed

• Measurement of HRQoL, in addition to more objective clinical outcomes of disease

such as disease activity and damage in SLE patients, allows their more
pt

comprehensive assessment considering not only their clinical condition, but also
their physical, social and psychological functioning, that is their HRQoL.
ce

• Many generic instruments have undergone extensive validation and have been
adapted to multiple languages and cultures; however, they may not be sufficient to
Ac

capture symptoms or issues affecting the SLE patient. Therefore, disease-specific

questionnaires should be included in the assessment of HRQoL, as they might be
more sensitive to change than generic instruments and evaluate specific therapeutic
interventions in SLE clinical trials.
• Older age, poverty and lower educational level are strong socio-demographic
predictors of lower HRQoL in SLE. Other factors affecting QoL in these patients
include a lower baseline QoL, disease activity and organ damage. For the later, an
 “adaptability phenomenon” has been observed. Clinical manifestations associated
with QoL in SLE include cutaneous, NP, renal and musculoskeletal. Within
comorbidities fibromyalgia, depression and the MetS are recognized as affecting
these patients’ QoL. In turn, a diminished QoL leads to disability, impaired
relationships and suboptimal strategies to deal with stress.
• There are no specific therapeutic interventions aimed at improving these patients’
HRQoL; the use of belimumab, ACTH, DHEA and methotrexate (the later as

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glucocorticoid-sparing agent) have been associated with better scores in QoL.

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• Studies comparing different CYC regimens in LN patients in improving these
patients HRQoL have shown short lasting improvements in the high dose group.

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• The role of HCQ in improving HRQoL is still debatable.

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• CBT, MBCT, exercise and the development of optimal relationship between patients
and their physicians have shown to be beneficial as non-pharmacologic treatment
strategies.
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Funding
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This paper is not funded.

Declaration of interest
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The authors have no relevant affiliations or financial involvement with any

organization or entity with a financial interest in or financial conflict with the subject
pt

matter or materials discussed in the manuscript. This includes employment,

consultancies, honoraria, stock ownership or options, expert testimony, grants or
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patents received or pending, or royalties.

Ac

Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to
disclose.

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ce
Ac
Table 1. Relationship Between HRQoL and Disease Activity and Damage in SLE Patients in Selected Studies

Author, Year, Study design, HRQoL Disease HRQoL and Disease Activity HRQoL and Damage

t
Country Number of Instrument Activity / (correlation coefficients) (correlation coefficients)

rip
(Reference) patients Damage
Instruments

c
Stoll T, et al., Cross-sectional; SF-36 BILAG / SDI SF-36 scores had weak to Weak negative correlation

us
United n=150 moderate correlation with BILAG between physical function and
Kingdom, 1997 scores (r = -0.27 to -0.40, p < damage (r = -0.30, p< 0.0001)

an
[16] 0.01)

Thumboo J, et Cross-sectional; SF-36 BILAG / SDI SF-36 subscale scores weakly SF-36 subscale scores

M
al., Singapore, n=118 correlated with BILAG scores (r weakly correlated with SDI (r = -
1999 [17] = -0.37 to 0.15) 0.25 to 0.23)

d
Gladman DD, et Cross-sectional; SF-36 SLEDAI / SDI No correlation between SF-36 No correlation between SF-36
al., Canada, n=119
te and SLEDAI scores (r = -0.27 to and SDI (r = -0.24 to 0.09)
ep
1997 [18] 0.20)

Fortin P, et al., Longitudinal, n=96 SF-36 SLAM-R, SF-36 subscales except role SDI correlated only with the
c

Canada, 1998 SLEDAI / SDI emotional were correlated with physical function subscale of SF-
Ac

[19] SLAM-R (- 0.29 to -0.41, P ≤ 36 (r = - 0.28, p≤ 0.01)

0.05 - ≤ 0.0001)

Only SF-36 subscales vitality

 and social function were
correlated with SLEDAI (r = -
0.26, p ≤ 0.01, other correlations
ranged from -0.03 to – 0.20)

t
rip
Leong KG, et Cross-sectional; SLEQOL SLEDAI, SLAM / No o negligible correlation with No o negligible correlation with
al., Singapore, n=275 SDI SLEDAI (r = 0.022) and SLAM (r SDI (r = 0.054)

c
2005 [20] = 0.018)

us
Aggarwal R, et Longitudinal, n=167 EQ-5D SLEDAI / SDI EQ-5D had weak negative EQ-5D has weak positive
al. USA, 2009 correlation with SLEDAI correlation with SDI (r = 0.20)

an
SF-6D
[21]
(r = -0.22) SF-6D had weak negative
SF-36
correlation with SDI (r = - 0.22)

M
SF-6D had weak negative
correlation with SLEDAI SF-36 scores (PCS, MCS) had no
correlation with SDI (PCS, r = -

d
(r = -0.23)
0.06; MCS, r = - 0.09)
te SF-36 scores (PCS, MCS) had
ep
no correlation with SLEDAI
(PCS, r = -0.13; MCS, r = - 0.10)
c

González- Cross-sectional; LupusQoL SLEDAI / SDI Only Lupus QoL subscales Only Lupus QoL subscale
Ac

Rodríguez V, et n=115 (Spanish physical health (r = -0.22, P = physical health (r = -0.22, p =

al. Spain, 2010 version) 0.05) and body image (-0.23, P= 0.05) was weakly correlated with
[22] 0.05) were weakly correlated SDI
with SLEDAI, other correlations
 ranged from -0.06 to -0.19)

García- Cross-sectional; SF-36 Mex-SLEDAI / SF-36 had weak correlation with SF-36 weakly correlated with SDI
Carrasco M, et n=127 SDI Mex-SLEDAI (r = -0.26, p= (r = -0.28, p =0.001)
LupusQoL

t
al. Mexico, 0.003)

rip
LupusQoL moderately correlated
2012 [23]
Lupus QoL had weak correlation with SDI (r = - 0.38, p <0.0001)
with Mex-SLEDAI (r = -0.25, p =

c
0.004)

us
Jolly M, et al. Cross-sectional; LupusPRO PGA, SLEDAI, HRQoL scores of Lupus PRO HRQoL scores of Lupus PRO

an
USA, 2012 [24] n=18 LFA, BILAG / correlated moderately with PGA correlated moderately with
SDI (r = -0.3, P = 0.001), SLEDAI (r damage (r = -32, p = 0.01)
= -0.32, p = 0.001), LFA (r = -

M
0.29, p = 0.002) and weakly with
mucocutaneous BILAG (r = -

d
0.23, p = 0.06), musculoskeletal

te BILAG (r = - 0.22, p = 0.08) and

vasculitis BILAG (r = - 0.21, P=
ep
0.09)

Duruöz MT, et Cross-sectional; Turkish L- SLEDAI-2K LQoL-TR had poor correlation

c

al. Turkey, 2017 n=55 QoL (LQoL- with SLEDAI-2K (r= 0.29, p
Ac

[25] TR) =0.1)

Kasturi S, et al. Cross-sectional; PROMIS SELENA- PROMIS CAT had week or no PROMIS CAT had generally week
SLEDAI, PGA / correlation with SELENA- or no correlation with SDI (r = -
USA, 2017 [26] n=204 CAT SDI SLEDAI (r = -0.4 –to 0.22) 0.31 to 0.20) with the highest
correlations in the domains of
physical function (r = -0.27) and
PROMIS CAT had weak to mobility (r = - 0.31)

t
rip
moderate correlation with PGA
(r = -0.35 to 0.37) with the
highest correlation in the

c
domains of physical function (r =

us
-0.29), mobility (r = -0.35) and
pain interference (r = 0.37)

an
Kasturi S, et al. Cross-sectional; PROMIS10 SELENA- PROMIS10 physical health PROMIS10 physical health scores
USA, 2018 [27] n=204 SLEDAI / SDI scores had no correlation with had weak correlation with SDI (r =

M
SLENA-SLEDAI (r = -0.14) -0.20)

d
te PROMIS10 mental
scores had no correlation with
health PROMIS10 mental health scores
had no correlation with SDI (r = -
ep
SLENA-SLEDAI (r = -0.16) 0.12)

Azizoddin DR, Cross-sectional; LupusPRO SELENA- HRQoL scores of Lupus PRO Only reported no correlation
c

et al. USA, n=131 version 1.8 SLEDAI, PGA / correlated moderately with PGA between lupus symptoms
Ac

2018 [28] (r = -0.34, p < 0.001), SELENA- LupusPRO domain and SDI (r = -
SDI
SLEDAI (r = -0.32, p = 0.001) 0.05, p = 0.55)
 Non-HRQoL scores of Lupus
PRO correlated moderately with

t
PGA (r = -0.32, p = 0.001),

rip
SELENA-SLEDAI (r = -0.29, P =
0.003)

c
Baba S, et al. Longitudinal; n=233 SF-36 SLEDAI-2K / SF-36 subscales / summary Physical functioning SF-36

us
Japan, 2018 SDI scores had no correlation with domain had strong negative
[29] SLEDAI (r = - 0.06 to - 0.09) correlation with SDI (r= -0.47, p

an
<0.05). Other SF-36 domains had
weak o no correlation with SDI (r=

M
-0.13 to -0.25)

PCS SF-36 had moderate

d
negative correlation with SDI (r= -

te 36, p <0.05)

MCS SF-36 had no correlation

ep
with SDI (r= -0.08)
c
Ac

BILAG index: British Isles Lupus Assessment Group index; SDI: Systemic Lupus International Collaborating Clinics/ American College of
Rheumatology DAMAGE index; SLEDAI: Systemic Lupus Erythematosus Disease Activity Index; SLEDAI-2K: SLEDAI-2000; Mex-SLEDAI:
Mexican-SLEDAI; SELENA-SLEDAI: Safety of Estrogens in Systemic Lupus Erythematosus National Assessment-SLEDAI; SLAM index: Systemic
Lupus Activity Measure Index; LFA: Lupus Foundation of America definition of flare; PGA: Physician Global Assessment; PCS: physical
component summary of SF-36; MCS: mental component summary of SF-36.

t
c rip
us
an
M
d
te
c ep
Ac
Table 2. Characteristics of Some Generic and Disease-specific Measures of Health-related Quality of Life Used in SLE

Instrumen Number of Domains assessed Score range / Time to Time Psychometric properties

t
ts [Ref] items interpretation complete frame

rip
Generic

c
SF-36 [16, 36 Physical functioning, role 0-100 < 10 Prior 4 Internal consistency: Yes

us
physical, social functioning, minutes weeks
51] Higher score indicates Reliability: No
bodily pain, mental health,
better QoL.

an
role emotional, vitality and Validity: No
general health perceptions.
Responsiveness (sensitivity to

M
Two summary measures: PCS The two summary change): No
and MCS*. scales PCS and MCS
Cross-cultural adaptation and

d
are scored using
validation: Yes
te norm-based methods.
A score of 50 reflects Floor/ceiling effects: not
ep
an average score with assessed
respect to the general
c

population.
Ac

Scores < 50 reflect

less than average
health
 Scores > 50 reflect
better than average
health.

t
rip
EQ-5D 5 plus a Visual Mobility, self-care, usual 0 (death or health 2 minutes Not stated Internal consistency: No
[52] Analog Scale activities, pain/discomfort, worse than death) to

c
Reliability: No
and 1.0 (best imaginable

us
(VAS)
health) Validity: No
anxiety/depression.

an
VAS: 0 (worst Responsiveness (sensitivity to
imaginable health change): Yes
state) to 100 (best

M
Cross-cultural adaptation and
imaginable health
validation: No
state).

d
Floor/ceiling effects: not
te reported
c ep
Ac
SF-6D [53] 6 Physical functioning, role Single numeric value < 5 minutes Prior 4 Internal consistency: No
limitations, social functioning, ranging from 0.296 weeks
Reliability: No
pain, mental health, and (worst possible
vitality. health, worse than Validity: No

t
being dead) to 1.0

rip
Responsiveness (sensitivity to
(perfect health).
change): Yes

c
Cross-cultural adaptation and

us
validation: Yes

an
Floor/ceiling effects: none

M
d
te
c ep
Ac
PROMIS Items are Physical function, mobility, PROMIS CAT is Each CAT Prior 7 Internal consistency: Yes
CATs [26, dynamically pain behavior, pain scored through the takes 1-2 days
Reliability: Yes
54] selected for interference, ability to Assessment Center minutes
administration participate in social roles, using a T score Validity: Yes

t
from an item satisfaction with social roles, metric, in which the

rip
bank, based fatigue, sleep disturbances, mean in the US Responsiveness (sensitivity to

upon the applied cognition-abilities, general population is change): not assessed in SLE

c
respondent’s anger, anxiety and 50 with an SD of 10.

us
Cross-cultural adaptation and
previous depression.
validation: PROMIS item
Higher T scores
answers. banks have been translated
reflect more of the

an
Usually 4-12 into many other languages
characteristic being
items per CAT. (Spanish, German, Dutch,
measured. Chinese, etc.). Additional

M
studies are needed to validate
PROMIS CAT in non-English–

d
speaking patients.

te Floor/ceiling effects: less

significant than with the SF-36
ep
and LupusQoL.

PROMIS10 10 Overall physical health, PROMIS10 is scored < 2 minutes Prior 7 Internal consistency: Yes
c

[27] mental health, social health, into global physical days

Reliability: yes
Ac

pain, fatigue, and overall health and global

perceived quality of life. mental health Validity: Yes
components using a
T score metric, in Responsiveness (sensitivity to
 which the mean in change): not assessed in SLE
the US general
Cross-cultural adaptation and
population is 50
validation: PROMIS item banks
(SD10).

t
have been translated into many

rip
Higher scores reflect other languages (Spanish,
better functioning. German, Dutch, Chinese, etc.).

c
Additional studies are needed

us
to validate PROMIS 10 in non-
English–speaking patients

an
Floor/ceiling effects: not
assessed.

M
Specific

d
LupusQoL 34 Physical health, emotional 0-100 < 10 Prior 4 Internal consistency: Yes
[55] health,
planning,
body
te
image,
fatigue,
pain,
intimate
Higher score indicates
minutes weeks
Reliability: Yes
ep
better QoL
relationships and burden to Validity: Yes
others.
Responsiveness (sensitivity to
c

change): No
Ac

Cross-cultural adaptation and

validation: Yes
 Floor effects: Yes

Ceiling effects: Yes

SLEQOL 40 Physical functioning, 40-280 < 5 minutes One week Internal consistency: Yes

t
rip
[20] activities, symptoms,
Higher score indicates Reliability: Yes
treatment, mood, and self-
worse QoL.
image. Validity: Yes

c
us
Responsiveness (sensitivity to
change): Yes

an
Cross-cultural adaptation and
validation: Yes

M
Floor/ceiling effects: not
assessed

d
L-QoL
[56]
25
impact of
te
List of items assessing the
SLE and its
0-25 < 5 minutes Not
reported
Internal consistency: Yes
ep
Higher score indicates Reliability: Yes
treatment on the patient. The
worse QoL/
questionnaire is based on the Validity: Yes
c

needs-based QoL model.

Responsiveness (sensitivity to
Ac

change): Not reported

Cross-cultural adaptation and

 validation: Yes

Floor/ceiling effects:
interpretation difficult (poor

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methodological quality).

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LupusPRO 44 HRQOL domains: lupus 0-100 < 10 Prior 4 Internal consistency: Yes

an
[24] symptoms, physical health, minutes weeks
Higher score indicates Reliability: Yes
pain–vitality, emotional
better QoL

M
health, body image, cognition, Validity: Yes
procreation, and lupus
Responsiveness (sensitivity to

d
medications
change): Yes
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Non-HRQOL: social support
and coping, desires and goals,
Cross-cultural adaptation and
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validation: Yes
and satisfaction with medical
care. Floor effects: Yes
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Ceiling effects: No

* MCS: Mental Component Summary; PCS: Physical Component Summary

Figure 1: Interaction Between Different Aspects of HRQoL in SLE Patients

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an
M
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HRQoL: Health-related Quality of Life. ADL: Activities of daily living.
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Adapted with permission from Phuti A, et al[130].
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