Factors associated with health-related quality of life in Peruvian patients with systemic lupus erythematosus

Abstract

Objective

In this paper, we aim to define factors associated with health-related quality of life (HRQoL) in Mestizo patients with systemic lupus erythematosus (SLE).

Methods

We evaluated patients with SLE from Peru’s two largest hospitals between October 2012 and July 2015 to ascertain HRQoL. Using a standard protocol, we incorporated demographic characteristics, clinical manifestations and treatment in our analysis. HRQoL was measured with the LupusQoL, disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and damage was appraised with the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) damage index (SDI). The associations between the LupusQoL and these variables were examined using linear regression models. Model selection was based on backward elimination.

Results

A total of 277 patients fit the inclusion criterion. Of these, 254 (91.7%) were female, the median (interquartile range, IQR) age at diagnosis was 41.5 (33.8–51.8) years, disease duration was 6.5 (2.7–11.3) years. The HRQoL domains most affected were the following: burden to others, fatigue, and intimate relationships.

Through multivariate analysis, we determined that older age at diagnosis, higher disease activity, damage, and immunosuppressive drug use were negatively associated with HRQoL. Further, we found that higher socioeconomic status, disease duration, and antimalarial use were positively associated with HRQoL.

Conclusion

Age at diagnosis, disease activity, damage, and use of immunosuppressive drugs were negatively associated with HRQoL; high socioeconomic status, disease duration, and use of antimalarials were positively associated with HRQoL.

Keywords

Systemic lupus erythematosus health-related quality of life Hispanic Mestizo

Introduction

Systemic lupus erythematosus (SLE) patients often have decreased quality of life (QoL); SLE has the capacity to affect aspects of both their physical and mental health.^1–4 Furthermore, the assessment of health-related QoL (HRQoL) is important because it provides unique information that is not captured by measurements of disease activity, damage or medication adverse effects.⁵

HRQoL is an individual’s perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns.⁶ Most studies concerning HRQoL have focused on patients treated at American or European tertiary centers, primarily Whites. However, researchers have shown that HRQoL differs significantly in other groups of patients with SLE. One of the first studies to address these patients found that African descendants and Mestizo patients with SLE had poorer outcomes, like higher mean arterial pressure and higher creatinine; they also had lower annual household incomes, compared with Whites.⁷ Furthermore, data from the Lupus in Minorities: Nature versus Nurture (LUMINA) cohort indicated that socioeconomic–demographic variables (such as older age, poverty, lower levels of education), and psychological, behavioral, and cultural variables (e.g. higher degrees of helplessness, abnormal illness-related behaviors, and inadequate social support) were predictors of poor HRQoL in patients with SLE.¹ This finding was important because researchers have also determined that low levels of self-perceived overall health early in the course of the disease appear to precede poor outcomes.⁸ These results suggest the value of determining HRQoL for SLE patients, particularly among understudied populations.

Reaching an understanding of the impact of SLE on patients’ lives is crucial in order to provide better management and care. In recognition of this significance, one of the 14 quality indicators recommended by the European League Against Rheumatism (EULAR)⁹ is the assessment of HRQoL in every patient with SLE at least once per year.

Although HRQoL has been evaluated in SLE patients primarily by generic and non-specific tools like the Medical Outcomes Study Short Form 36 (SF-36), this index did not correlate or correlated weakly with disease activity or damage.^10,11 However, a specific tool like the LupusQoL may be able to better reflect changes in HRQoL caused by different levels of disease activity or damage,^12–15 supporting the relevance of using this questionnaire in SLE patients.

Despite growing awareness of the importance of HRQoL in Latin America, research on HRQoL has been limited and is not always consistent. Among those limited studies, in Mexico, Etchegaray-Morales et al.¹² used LupusQoL and associated poor HRQoL with disease activity, damage, fibromyalgia and depression. In Chile, Calderon et al.¹⁶ demonstrated that depression is associated with poor physical and mental components of HRQoL in SLE; further, they found that disease activity and damage are associated with lower physical components. In Brazil, Pinto et al.¹⁷ observed that patients with SLE with mild or inactive disease have impaired aerobic capacity and HRQoL compared with controls. Comparatively, in Argentina, LupusQoL was associated neither with disease activity nor with damage.¹⁸

Research regarding the factors associated with HRQoL in Latin American patients with SLE remains limited. In order to address this knowledge gap toward the goal of improving management and care, we conducted this study in order to define factors associated with HRQoL in predominantly Mestizo patients with SLE using a disease-specific tool for HRQoL (LupusQoL).

Methods

Patients. We enrolled 277 patients who had routine rheumatologic care at the two largest hospital of the Peruvian Social Security Administration. Enrollment at Hospital Guillermo Almenara Irigoyen started in January 2012. In summary, all SLE patients presenting to the rheumatology department of this hospital were invited to participate in this study. Enrollment at Hospital Edgardo Rebagliati Martins started in January 2015. Each hospital’s institutional review board approved the study. Patients who signed the informed consent were evaluated with a common protocol which included an interview, medical records review, physical examination and laboratory tests. We included data generated by the patients at both locations through July 2015.

SLE was defined using the revised and updated American College Rheumatology (ACR) criteria.¹⁹ Demographic data included age at diagnosis, sex, socioeconomic status (SES) and ethnicity; SES was defined using the Graffar’s method,²⁰ and ethnicity was self-reported in the following categories: White, Mestizo, African Latin-American, Indigenous, Asian, and Other.

Clinical variables included disease duration, disease activity (ascertained with the SLEDAI²¹), disease damage (ascertained with the SLICC/ACR damage index (SDI)²²), and medications, including prednisone (recorded as current daily dose and time of exposure), antimalarials, and immunosuppressive drugs (recorded as current, past or never used).

HRQoL was measured with the LupusQoL, using the validated Spanish language version for Peru. This questionnaire includes 34 items and 8 domains, including physical health, emotional health, body image, pain, planning, fatigue, intimate relationships, and burden to others. The domain score ranged from 0 to 100, with 100 being the highest HRQoL.²³

Statistical analyses

We examined the associations between the LupusQoL and demographic, clinical manifestations, and treatment using univariate and multivariate linear regression models. Model selection was based on backward elimination.

All statistical analyses were performed using SPSS v. 21.0 (IBM, Chicago, IL, USA).

Results

A total of 277 SLE patients were included; of these, 254 (91.7%) were female, the median age at diagnosis was 41.5 [interquartile range (IQR): 33.8–51.8] years, and median disease duration was 6.5 (2.7–11.3) years. The median SLEDAI was 4.0 (1.0–6.0) and the SDI was 1.0 (0.0–2.0). The duration of exposure to prednisone was 6.0 (2.0–11.0) years. Median current prednisone dose was 5.0 (5.0–10.0) mg/d. Antimalarial and immunosuppressive drugs were currently used by 237 (85.6%) and 153 (55.2%) patients, respectively. Patient characteristics are depicted in Table 1.

Table 1

Characteristics of SLE patients

Characteristic
Age, years, median (IQR)	41.5 (33.8–51.8)
Sex, female, n (%)	254 (91.7)
Socioeconomic status
High/medium–high	140/276 (50.5)
Medium	95/276 (34.4)
Low/medium–low	41/276 (14.9)
Ethnic group
Mestizo, n (%)	270 (97.5)
White, n (%)	6 (2.2)
African Latin–American, n (%)	1 (0.4)
Disease duration, years, median (IQR)	6.5 (2.7–11.3)
SLEDAI, median (IQR)	4.0 (1.0–6.0)
SDI, median (IQR)	1.0 (0.0–2.0)
Current dose of prednisone, mg/d, median (IQR)	5.0 (5.0–10.0)
Time of exposure to prednisone, years, median (IQR).	6.0 (2.0–11.0)
Antimalarial use
Never, n (%)	16 (5.8)
Past, n (%)	24 (8.7)
Current, n (%)	237 (85.6)
Immunosuppressive drug use
Never, n (%)	65 (23.5)
Past, n (%)	59 (21.3)
Current, n (%)	153 (55.2)
Physical health, median (IQR)	75.0 (62.5–87.5)
Pain, median (IQR)	83.3 (58.3–91.7)
Planning, median (IQR)	83.3 (58.3–100.0)
Intimate relationships, median (IQR)	75.0 (37.5–100.0)
Burden to others, median (IQR)	58.3 (29.2–83.3)
Emotional health, median (IQR)	75.0 (54.2–87.5)
Body image, median (IQR)	80.0 (55.0–95.0)
Fatigue, median (IQR)	68 (43.8–87.5)

IQR: interquartile range; SDI: SLICC/ACR damage index; SLICC: Systemic Lupus International Collaborating Clinics; ACR: American College of Rheumatology.

The domains most affected were burden to others, fatigue, and intimate relationships, their medians being 58.3 (29.2–83.3), 68 (43.8–87.5) and 75.0 (37.5–100.0), respectively.

Associated factors with health-related quality of life

Demographic features

In the multivariable analysis (Table 2), age at diagnosis had a statistically significant association with physical health [B = −0.60; confidence interval (CI) 95% (−0.78 to −0.42); p < 0.001], pain [B = −0.56; CI 95% (−0.76 to −0.35); p < 0.001], planning [B = −0.52; CI 95%(−0.76 to −0.29); p < 0.001], intimate relationships [B = −0.99; CI 95%(−1.36 to −0.64); p < 0.001], emotional health [B = −0.26; CI 95%(−0.47 to −0.05); p = 0.017], body image [B = −0.24; CI 95%(−0.46 to −0.02); p = 0.017], and fatigue [B = −0.29; CI 95%(−0.51 to −0.07); p = 0.009]. High socioeconomic status (SES) was positively associated with planning, intimate relationships, emotional health, and fatigue [B = 12.79; CI 95%(3.48 to 22.09), p = 0.007; B = 13.95; CI 95%(1.78 to 26.12), p = 0.025; B = 11.53; CI 95%(3.46 to 19.59), p = 0.005 and B = 10.47; CI 95%(1.63 to 19.31); p = 0.020, respectively].

Table 2

Association between the domains of the Lupus Quality of Life questionnaire and demographic, clinical manifestations and treatment by multivariable analyses

	PH B (CI 95%)	P B (CI 95%)	Pl B (CI 95%)	IR B (CI 95%)	BO B (CI 95%)	EH B (CI 95%)	BI B (CI 95%)	F B (CI 95%)
Age at diagnosis	−0.60 (−0.78 to −0.42); p < 0.001	−0.56 (−0.76 to −0.35); p < 0.001	−0.52 (−0.76 to −0.29); p < 0.001	−0.99 (−1.36 to −0.64); p < 0.001		−0.26 (−0.47 to −0.05); p = 0.017	−0.24 (−0.46 to −0.02); p = 0.030	−0.29 (−0.51 to −0.07); p = 0.009
SES
Low			Ref.			Ref.		Ref.
Medium			2.85 (−6.81 to 12.50); p = 0.563	9.68 (−3.09 to 22.44); p = 0.127		6.12 (−2.32 to 14.57); p = 0.155		8.97 (−0.28 to 18.21); p = 0.057
High			12.79 (3.48 to 22.09); p = 0.007	13.95 (1.78 to 26.12); p = 0.025		11.53 (3.46 to 19.59); p = 0.005		10.47 (1.63 to 19.31); p = 0.020
Disease duration				0.66 (0.06 to 1.27); p = 0.032	0.80 (0.30 to 1.30); p = 0.002	0.55 (0.14 to 0.95); p = 0.008
SDI	−1.93 (−3.80 to −0.05); p = 0.044
SLEDAI	−0.82 (−1.40 to −0.25); p = 0.005	−1.00 (−1.64 to −0.35); p = 0.002	−0.89 (1.64 to −0.15); p = 0.019		−0.88 (−1.71 to −0.05); p = 0.038			−0.74 (−1.44 to −0.03); p = 0.041
Antimalarials
Never	Ref.				Ref.		Ref.
Past	13.28 (0.28 to 26.29); p = 0.045				22.26 (3.79 to 40.72); p = 0.018		29.18 (13.48 to 44.89); p < 0.001
Current	154.37 (4.23 to 24.52); p = 0.005				18.09 (3.67 to 32.52); p = 0.014		18.01 (5.72 to 30.30); p = 0.004
Immunosuppressive drugs
Never	Ref.	Ref.	Ref.		Ref.	Ref.	Ref.
Past	−11.45 (−18.86 to −4.05); p = 0.002	−12.61 (−20.86 to −4.37); p = 0.003	−15.06 (−24.52 to −5.59); p = 0.002		−10.41 (−20.76 to −0.07); p = 0.049	−8.79 (−17.08 to −0.49); p = 0.038	−11.10 (−20.03 to −2.16); p = 0.015
Current	−8.50 (−14.44 to −2.55); p = 0.005	−7.18 (−13.85 to −0.51); p = 0.035	−11.08 (−18.67 to −3.49); p = 0.004		−7.35 (−15.89 to 1.19); p = 0.091	−5.72 (−12.36 to 0.92); p = 0.091	−5.78 (−12.98 to 1.41); p = 0.115

PH: physical health; EH: emotional health; BI: body image; P: pain; Pl: planning; F: fatigue; IR: intimate relationships; BO: burden to others; SES: socioeconomic status; SDI: SLICC/ACR damage index; SLEDAI: Systemic Lupus Erythematosus Disease Activity Index.

Clinical features

Disease duration was statistically associated with intimate relationships [B = 0.66; CI 95%(0.06 to 1.27); p = 0.032], burden to others [B = 0.80; CI 95%(0.30 to 1.30); p = 0.002], and emotional health [B = 0.55; CI 95%(0.14 to 0.95); p = 0.008]. SDI was negatively associated with physical health [B = −1.93; CI 95%(−3.80 to −0.05); p = 0.044]. Furthermore, SLEDAI was negatively associated with physical health [B = −0.82; CI 95%(−1.40 to −0.25); p = 0.005], pain [B = −1.00; CI 95%(−1.64 to −0.35); p = 0.002], planning [B = −0.89; CI 95%(1.64 to −0.15); p = 0.019], burden to others [B = − 0.88; CI 95%(−1.71 to −0.05); p = 0.038], and fatigue [B = −0.74; CI 95%(−1.44 to −0.03); p = 0.041].

Treatment features

The current and past use of antimalarials was positively associated with physical health [B = 154.37; CI 95%(4.23 to 24.52); p = 0.005 and B = 13.28; CI 95%(0.28 to 26.29); p = 0.045, respectively], burden to others [B = 18.09; CI 95%(3.67 to 32.52); p = 0.014 and B = 22.26; CI 95%(3.79 to 40.72); p = 0.018, respectively] and body image [B = 18.01; CI 95%(5.74 to 30.30); p = 0.004 and B = 29.18; CI 95%(13.48 to 44.89); p < 0.001, respectively]. Moreover, current and past use of immunosuppressive drugs was negatively associated with physical health [B = −8.50; CI 95%(−14.44 to −2.55); p = 0.002 and B = −11.45; CI 95%(−18.86 to −4.05); p = 0.002, respectively], pain [B = −7.18; CI 95%(−13.80 to −0.51); p = 0.035 and B = −12.61; CI 95%(−20.86 to −4.37); p = 0.003, respectively], planning [B = −11.08; CI 95%(−18.67 to −3.49); p = 0.004 and B = −15.06; CI 95%(−24.52 to −5.59); p = 0.002, respectively], body image [B = −5.78; CI 95%(−12.98 to 1.41); p = 0.115 and B = −11.10; CI 95%(20.03 to −2.16); p = 0.015, respectively] and also the past use of these drugs was statistically negatively associated with burden to others [B = −10.41; CI 95%(−20.76 to −0.07); p = 0.029] and emotional health [B = −8.79; CI 95%(−17.08 to −0.49); p = 0.038].

Discussion

We found that Latin American SLE patients were most affected by three domains: intimate relationships, burden to others and fatigue. The effect on intimate relationships is an unusual finding, contrary to a multinational European study finding that this domain was the least affected (mean score of 63.6).²⁴ On the other hand, our findings regarding burden to others and fatigue are consistent with findings from other countries. For example, Italian SLE patients routinely scored higher effects in the domains of burden to others (66.0 ± 27.6), emotional health (71.9 ± 23.7) and fatigue (73.9 ± 22.8)(13); in UK patients, fatigue was the most highly affected domain (median 56.3).²⁵ We hypothesize that our patients experience more fatigue because this symptom makes them more vulnerable to suffering depression and anxiety, factors which would be associated with the emotional domain, worsening, therefore, their QoL. Of note, we are reporting an association between the use of antimalarials and a better HRQoL for the first time.

Age was associated with all domains, with the exception of burden to others; these associations are consistent with previous reports from the USA and UK.^14,25,26 Older age at diagnosis has been associated with a poor outcome, in terms of both damage accrual and mortality.²⁷ Likewise, it is associated with a five-fold increase in fracture occurrence.²⁸ Also, the prevalence of renal disease in late-adult onset is higher (58%), with a significantly lower creatinine clearance compared with childhood onset.²⁹ Consequently, higher age is a predictor of poor mental and physical health, and in turn, a lower HRQoL.

High and medium SES correlated positively with a higher HRQoL in four domains: planning, emotional health, intimate relationships and fatigue. However, these findings must be interpreted with caution because low SES is associated with several adverse outcomes like increased damage, work disability and mortality;³⁰ as such, a better SES could be related to better support and occupations with a lower physical demand, rather than SLE-related factors. Likewise, poverty has been associated with lower HRQoL scores and higher educational level with a higher HRQoL scores.²⁶ In addition, we acknowledge that lower social support due to several biases: less access to healthcare, less knowledge about SLE, less education, and poor incomes may affect HRQoL scores in SLE patients with low SES.³¹

A longer disease duration was associated with a higher HRQoL in the domain of burden to others; we suggest that this finding could be related to adequate social support. One trial in the USA found that social support is one of the most important factors in predicting the physical and mental health of SLE patients.³²

Disease activity and damage have not been consistently reported to be associated with HRQoL. Several studies, including a multinational pediatric cohort, as well as others from Switzerland, Sweden, Italy, the USA and Mexico found higher disease activity associated with lower HRQoL;^{3,13,14,33–35} comparatively, studies from Brazil and Turkey did not.^36,37 Likewise, in studies from China, Japan, UK, USA and Mexico, higher damage was found to be associated with lower HRQoL,^{2,14,25,33,38} but a study from Brazil did not find the association.³⁹ More consistently, remission and low disease activity status have been found to be associated with higher HRQoL.^40,41 In our study, disease activity was negatively associated with physical health, pain, planning, burden to others and fatigue; disease damage was negatively related to physical health and intimate relationships.

The use of immunosuppressive drugs (current or past) could reflect more severe disease, and this could explain its positive association with physical health, pain, planning, burden to others, emotional health and body image. However, these drugs have the capacity to play a positive or negative role, depending on the good outcomes or the adverse reactions (e.g. increased risk of severe infections, gonadal damage, and malignancy).⁴² A Hong Kong trial concluded that patients with lupus nephritis who were consuming prednisone plus mycophenolate had better QoL scores versus those that were taking prednisone plus oral cyclophosphamide.⁴³ Additionally, several studies have shown the benefits of antimalarials: preventing flares, as well as reducing SLE activity, mortality, thrombotic events, and irreversible organ damage.^44–46 These effects could explain the association between antimalarial use and a higher HRQoL in some patients.

The LupusQoL questionnaire provides a complete assessment of the impact of disease in the patient’s daily life. Several investigators studied the components of this questionnaire and the relationship with multiple factors; for example, in Italian patients with SLE, the stress deriving from negative support affecting QoL and having an impact on disease symptoms.⁴⁷ Moreover, an Iranian study showed that severe anxiety and depression were associated with lower physical health, whereas the mental component was relatively similar to healthy individuals.⁴⁸ On the other hand, a study in Brazil found a significant correlation between neuropsychiatric symptoms and high activity of SLE or greater damage associated with the disease.³⁶ Furthermore, patients who had their disease controlled showed a higher independence level.³⁹ In addition, a good medical care is also important; SLE patients had emotional control, decreased pain and improved in other symptoms, generating a good QoL.³⁹

As our study was cross-sectional, one of the most significant limitations of our analysis is that we could not examine the cumulative dose of immunosuppressive drugs or determine the temporary relationship between the variables analyzed. Also, the LupusQoL does not allow comparison studies that use generic measures, like the Short Form-36. However, we consider these findings warrant reporting. Not only is this the largest study examining HRQoL in Latin America, this information might be used in order to establish programs that could improve the HRQoL in SLE patients.

In conclusion, in these Peruvian SLE patients, the domains most affected were intimate relationships, burden to others, and fatigue. The HRQoL is negatively influenced by age at diagnosis, damage, disease activity and immunosuppressive drugs; conversely, it is positively associated with disease duration, high socioeconomic status, and use of antimalarials.

Footnotes

Acknowledgments

The authors want to acknowledge Dr Cecilia Chung and Ms Alyson Dickson, MST, from Vanderbilt University Medical Center, Nashville, Tennessee, USA, for their critical review of this paper. All authors were involved in drafting or revising this article critically for important intellectual content, and all authors approved the final version to be published. Dr Claudia Elera-Fitzcarrald and Dr Manuel F Ugarte-Gil have full access to all of the data from the study and take responsibility for their integrity and the accuracy of the analyses performed.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Almenara Lupus Cohort was partially supported by two institutional grants from EsSalud (1483-GCGP-ESSALUD-2013 and 1733-GCGP-ESSALUD-2014).

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