Quality of Life Over Time in Patients With Systemic Lupus Erythematosus

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1 Arthritis & Rheumatism (Arthritis Care & Research) Vol. 59, No. 2, February 15, 2008, pp DOI /art , American College of Rheumatology ORIGINAL ARTICLE Quality of Life Over Time in Patients With Systemic Lupus Erythematosus BINDEE KURIYA, DAFNA D. GLADMAN, DOMINQUE IBAÑEZ, AND MURRAY B. UROWITZ Objective. To determine whether quality of life in patients with systemic lupus erythematosus (SLE) measured by the Short Form 36 (SF-36) changes over time and which patient- and disease-related factors influence such change. Methods. SLE patients who had >6 SF-36 evaluations during followup were identified from a database. Outcomes were slopes of scores of the 8 SF-36 domains as well as the physical and mental component scores. Based on the direction of the slope, patients were designated as unchanged, improved, or worsened. Linear regression models were used to test the contribution of risk factors to slopes. Nonparametric tests were used to evaluate risk factors between patterns of clinical change. Results. A total of 146 patients had >6 SF-36 evaluations in 1,047 visits over a mean SD period of years. During the interval, the majority of patients showed no change in the SF-36 domains and only a small minority demonstrated improvement. Physical and mental component scores were unchanged in 84.3% and 87.7% of patients whereas 4.1% and 7.5% improved, respectively. According to slopes of the domains and summary scores, only physical functioning demonstrated a significant decrease over time. There were no lupus disease features associated with decline in physical functioning except for the presence of fibromyalgia. Conclusion. The SF-36 in SLE patients with established disease changed little over an 8-year period. Changes in the SF-36 were not affected by disease activity, steroids, or damage accumulation during the interval, but were affected by the presence of fibromyalgia. INTRODUCTION The life expectancy of patients with systemic lupus erythematosus (SLE), although lower than the general population, has improved as a result of diagnostic and therapeutic advancements (1). With improved survival the impact of disease and treatment on quality of life, rather than quantity of life, emerged as an important consideration in the evaluation and management of SLE. The Systemic Lupus International Collaborating Clinics (SLICC) group has recommended that 3 domains be included in the description of patients with SLE: disease activity, accumulated damage, and quality of life (2). It was further recommended that the Medical Outcomes Study (MOS) Short Form 36 (SF-36) be used as the measure of quality of life in patients with SLE. The SF-36 is a valid Bindee Kuriya, MD, Dafna D. Gladman, MD, FRCPC, Dominque Ibañez, MSc, Murray B. Urowitz, MD, FRCPC: University of Toronto Lupus Clinic Toronto, Ontario, Canada. Address correspondence to Dafna D. Gladman, MD, FRCPC, Centre for Prognosis Studies in The Rheumatic Diseases, Toronto Western Hospital, 399 Bathurst Street, 1E- 410B, Toronto, Ontario, Canada, M5T 2S8. dafna. gladman@utoronto.ca. Submitted for publication April 16, 2007; accepted in revised form July 31, and reliable tool that captures the physical, psychological, and social impact of chronic diseases such as SLE (3 5). Health-related quality of life of patients with SLE is significantly worse and affects all health domains at an earlier age in comparison with patients with some other common chronic diseases (6). Previous studies have identified psychosocial (e.g., social support) and behavioral variables (e.g., helplessness, coping with illness) as being associated with quality of life in patients with SLE (7 11). However, inconsistent results have been reported regarding the influence of disease activity and damage on quality of life. Some studies have demonstrated a lack of correlation among these outcomes while others have shown disease variables to be strong predictors of quality of life (12 18). A recent review of quality of life in SLE concluded that there was no correlation with disease activity or damage (19). The use of different instruments to measure outcomes and the heterogeneity of patients examined may explain these conflicting results. Furthermore, most studies have been crosssectional and have examined quality of life at one point in time. Given that SLE is a recurrent relapsing disease, quality of life may show temporal variation. Therefore, longitudinal assessments may better reflect living with lupus over the long term. The goal of this study was to determine whether quality of life in patients with SLE, as measured by the SF-36, 181

2 182 Kuriya et al changes over time, and if so, to discern which patient- and disease-related factors influence such change. PATIENTS AND METHODS Patient selection. Outpatients attending the University of Toronto Lupus Clinic comprised the study population. All patients who met 4 of the American College of Rheumatology (ACR) criteria for classification of SLE (20,21) and had completed 6 SF-36 evaluations were included. Patients were followed in the clinic according to a standard protocol at 2 6-month intervals. Each assessment included demographic, clinical, and laboratory evaluations. All information was tracked on a computer database. Outcome measures. The standard version (4-week recall) of the MOS SF-36 was used. This self-administered questionnaire measures quality of life in 8 areas of perceived health: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. A ninth item relates to the change in health over time. Scores range from 0 to 100, with higher scores reflecting better quality of life. The SF-36 subscales can be summarized into 2 component scores: the physical component summary and the mental component summary. The summary scores are standardized to the Canadian population (mean SD score 50 10). Several advantages of the summary scores over the 8 subscales have been reported (3,22,23). In our clinic, patients complete the SF-36 once a year. Disease variables. Disease duration was defined as the time from the diagnosis of SLE made by a physician. Disease activity was measured both by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (24) and the adjusted mean SLEDAI (AMS) (25), which takes into account variable intervals between visits. The SLICC/ACR Damage Index (SDI) was used to score accumulated damage (26). Predictive and associated factors. Predictive factors at the time of the first SF-36 completion included age, education, ethnicity, disease duration, disease activity (SLEDAI-2K), disease damage (SDI), and medications (corticosteroids, antimalarials, immunosuppressive/cytotoxic drugs). Associated factors (in the interval from first to last SF-36 completion) included AMS, change in SDI, cumulative dose of steroids, percentage of interval on steroids, use of antimalarials, use of immunosuppressive agents, and presence of fibromyalgia (defined as diffuse pain associated with 11 classic fibromyalgia tender points) (27). Statistical analysis. The SF-36 over time was analyzed by running a linear regression model for each patient and each domain separately from which we obtained a slope and a P value. If the P value was not significant, we considered the patient unchanged. If the P value was 0.05 and the slope was 0, we considered the patient improved. If the P value was 0.05 and the slope was 0, we considered the patient worsened. We analyzed the results in 2 ways: slope as a continuous variable (irrespective of the P value) and categorical pattern of clinical change (unchanged, improved, or worsened as defined above). Linear regression models were used to test the contribution of predictive and associated factors to slopes. Nonparametric tests (Kruskal-Wallis, Mantel-Haenszel chi-square) were used to evaluate predictive and associated factors between patterns of clinical change. RESULTS Table 1. Characteristics of the systemic lupus erythematosus cohort* Characteristic At first SF-36 completion At end of interval Female sex 132 (90.4) Ethnicity White 110 (75.3) Other 36 (24.7) Secondary school 83 (59.3) education or higher Age at time of SF-36, mean SD years Disease duration, mean SD years SLEDAI-2K score, mean SD AMS score, mean SD SDI score, mean SD Steroid use ever 124 (84.9) 130 (89.0) Cumulative steroid dose, mean SD gm Antimalarial use 108 (74.0) 126 (86.3) Immunosuppressive agent use 69 (47.3) 90 (61.6) * Values are the number (percentage) unless otherwise indicated. SF-36 Short Form 36; SLEDAI-2K Systemic Lupus Erythematosus Disease Activity Index 2000; AMS adjusted mean SLEDAI; SDI Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. The descriptive characteristics of the 146 patients who had completed 6 SF-36 evaluations spanning a mean SD interval of years are shown in Table 1. More than 90% were women, and most were white; a large proportion had completed high school or a higher form of education. Mean SD age at diagnosis was years. Most patients were well into their disease, with a mean disease duration of 13.0 years at first SF-36 completion, and most had accrued damage, with a mean SDI score of The SLEDAI-2K score was 4.26 on average, suggesting mild-moderate disease activity requiring treatment. Indeed, the majority of patients had taken or were taking corticosteroids at the time of first SF-36 completion, with an average cumulative dosage of 38.6 gm. Three-quarters of the patients had taken or were taking antimalarial therapy and almost half of the patients had taken or were taking immunosuppressive drugs. During the interval, disease activity was stable while the SDI score increased by an average of 1.08 in 54.8% of the

3 Quality of Life in Patients With SLE 183 Table 2. Associated factors during the interval between the first and last Short Form 36 completion* Characteristic Value Disease duration, years Steroid use, no. (%) 110 (75.3) Cumulative steroid dose, gm Percentage of interval on steroids Antimalarial use, no. (%) 115 (78.8) Immunosuppressive agent use, no. (%) 83 (56.9) AMS score Worsened SDI score, no. (%) 80 (54.8) SDI accrued * Values are the mean SD unless otherwise indicated. See Table 1 for definitions. patients, from a mean of 1.30 at first SF-36 completion to 2.38 by last SF-36 completion. Steroid use decreased from 84.9% of patients to 75.3%, while antimalarial and immunosuppressive use increased (Table 2). At baseline, patients with SLE had a lower quality of life over all domains when compared with the general public (Figure 1). According to the slopes of the domains and summary scores, only physical function showed a significant decrease over time (Figure 2). The negative slope represents a worsening in quality of life in the physical function domain. Using the pattern of clinical change as unchanged, improved, or worsened quality of life, domains were unchanged over the interval (Figure 3). Figure 2. Mean slope and 95% confidence intervals for each of the 8 Short Form 36 (SF-36) domains and summary scores over the study period. PF physical functioning; RP role physical; BP bodily pain; GH general health; VT energy/vitality; SF social functioning; RE role emotional; MH mental health; PCS physical component summary; MCS mental component summary. Changes in the physical function domain were not affected by any demographic characteristics at onset or during the interval, except for ethnicity (Table 3). There was no statistically significant difference between white and nonwhite patients in the physical function component at first completion of the SF-36 (mean SD versus ; P 0.37). However, there was a difference in the slope of the SF-36 physical function component between white and nonwhite patients ( versus ; P 0.002). Disease activity and damage were also not predictive of worsening physical function. The same was true for all other domains and summary scores. Similarly, physical function at the last SF-36 completion was not affected by any of the associated features during the interval. Thus, the length of the interval, disease du- Figure 1. Radar plot comparing mean Short Form 36 (SF-36) scores of patients with systemic lupus erythematosus (SLE) and published norms for Canadian men and women (all ages). Each spoke on the plot represents a subcategory of the SF-36. Plots are read from the center outward along each spoke, with scores beginning with 0 and increasing to 100. PF physical functioning; RP role physical; BP bodily pain; GH general health; VIT energy/vitality; SF social functioning; RE role emotional; MH mental health. Circles all Canadians; squares patients with SLE. Figure 3. Patterns of change in domain and summary scores of the Short Form 36 (SF-36) over the 8-year interval. PF physical functioning; RP role physical; BP bodily pain; GH general health; VT energy/vitality; SF social functioning; RE role emotional; MH mental health; PCS physical component summary; MCS mental component summary. Solid bars improved; hatched bars unchanged; shaded bars worsened.

4 184 Kuriya et al Table 3. Baseline demographic and clinical predictors of change in physical function (linear regression model)* Characteristic at first SF-36 completion Female sex 0.44 White ethnicity Secondary school education or higher 0.71 Age at diagnosis 0.85 Age at first SF-36 completion 0.12 Disease duration 0.06 Fibromyalgia 0.02 Tender point count 0.04 SLEDAI-2K score 0.13 SDI score 0.62 Steroid use 0.45 Cumulative steroid dose 0.50 Antimalarial use 0.45 Immunosuppressive agent use 0.43 * See Table 1 for definitions. SF-36 physical functioning decreased in whites and increased in nonwhites. ration at last SF-36 completion, AMS, SDI at last SF-36 completion, and use of steroids, antimalarials, and immunosuppressive medications were not associated with change in SF-36. However, fibromyalgia did have an effect on quality of life. A total of 102 patients (69.9%) had a tender point count of 0 and 44 patients (30.1%) had tender point counts between 1 and 18. Of the latter, 27 (18.5%) had a tender point count 11. The correlation between tender point count and physical function was significant (r 0.17, P 0.04). When tender point count was classified as 11 or 11, then the slopes were significantly different (mean SD versus ; P 0.02). DISCUSSION SLICC has recommended the SF-36 as the measure of quality of life in SLE (2). At one point in time, healthrelated quality of life is an independent domain in the assessment of patients with SLE, and indeed has been shown to be lower in patients with SLE than in patients with other chronic diseases (6). We have confirmed this in the current study (Figure 1). Many studies have found no correlation between the SF-36 and disease activity (12,15,16). Others have found a relationship between the SF-36 and disease activity using the Systemic Lupus Activity Measure, or British Isles Lupus Assessment Group (18,24,25). Our study of patients with longstanding disease with low disease activity demonstrates that the majority of quality of life domains, as measured by the SF-36, do not change over time. This is similar to the study by Panopalis et al (28). The only domain that showed a decline over time was physical function. Changes in this domain were affected by ethnicity, with nonwhite patients showing slight improvement and white patients showing slight deterioration, but were not affected by other patient demographics or disease- or treatment-related factors. Another potential factor that P may have an impact is fibromyalgia (29,30). Our study indicates that patients with fibromyalgia with tender point counts 11, i.e., clinically important fibromyalgia, have greater deterioration of their physical function than patients with tender point counts 11. The strength of our study is that it represents a large cohort, and is one of the first to longitudinally assess quality of life. A potential weakness is that we assessed quality of life with a single instrument, the SF-36, an instrument that assesses status in the preceding month, whereas the patients were surveyed yearly. Thus we are describing landmark outcomes rather than outcomes over time. However, by choosing patients with a minimum of 6 SF-36 assessments and assessing slopes over the followup period, we are observing changes over time. We are also describing a select population of patients with established disease of 13 years duration and therefore results may not reflect what happens in early disease. However, the SF-36 was not found to be sensitive to change over 3 months in a cohort of patients from Singapore, where a new diseasespecific instrument, the SLE Quality of Life instrument, was developed and found to be sensitive to change (31). Furthermore, it is not possible to extrapolate these results to therapeutic trials in which patients are admitted with high disease activity and evaluated over a short period. Indeed, in at least 1 trial there was a significant difference in health-related quality of life measured by the SF-36 between drug-treated and placebo-treated patients (32). Nonetheless, at the late stage of the disease, quality of life remains low, even with a low level of disease activity. Therefore, health-related quality of life measured by the SF-36 is an important domain in the assessment of patients with SLE. It is not correlated with disease activity or damage at one point in time, but physical function may be adversely affected by the presence of fibromyalgia. In latestage disease, the SF-36 is not sensitive to change over a period of 8 years. However, in short-term clinical trials and in early disease the SF-36 may be sensitive to change. 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