Prediction of Damage Accrual in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index

Background:The Systemic Lupus International Collaborating Clinics (SLICC) Frailty Index (SLICC-FI) has been developed as a predictor of outcomes in SLE patients1-3. It combines disease activity, damage, comorbidities and health-related quality of life measures.Objectives:To evaluate the SLICC-FI as a predictor of damage accrual in systemic lupus erythematosus (SLE) patients.Methods:Patients from a multi-ethnic, multi-center US lupus cohort were included. Damage was ascertained with the SLICC/American College of Rheumatology (ACR) damage index (SDI) at last visit. The first visit in which the SLICC-FI could be derived was considered as the baseline visit. Univariable and multivariable Poisson regression models were performed to determine the association between the baseline SLICC-FI and last SDI, adjusted for sex, age at diagnosis, ethnicity, insurance, prednisone daily dose, antimalarial and immunosuppressive drug use at baseline. Age and gender were included a priori in the multivariable model, the other variables were included if they had a p<0.10 in the univariable models.Results:Of the 503 patients included, 454 (90.3%) were female with mean (SD) age 37.1 (12.5) years at diagnosis; 174 (34.6%) were African-American, 144 (28.6%) were Caucasians, 86 (17.1%) Hispanics (Texas), and 99 (19.7%) were Hispanics (Puerto Rico). The mean (SD) baseline SLICC-FI was 0.26 (0.06). The final mean (SD) SDI score was 1.9 (2.2). Higher SLICC-FI scores at baseline predicted greater damage accrual in the univariable analysis [Estimate=5.058, (SE=0.498); p<0.0001]. The SLICC-FI remained associated with damage accrual in the multivariable model, after adjustment for possible confounders [Estimate= 3.561 (SE=0.538); p<0.0001].Conclusion:The SLICC-FI predicts damage accrual in SLE patients from a multi-ethnic cohort, supporting the importance of this index in the evaluation of SLE patients, combining several aspects of the disease.References:[1]Legge A, Kirkland S, Rockwood K, et al. Construction of a Frailty Index as a Novel Health Measure in Systemic Lupus Erythematosus. J Rheumatol. 2020; 47: 72-81[2]Legge A, Kirkland S, Rockwood K, et al. Evaluating the Properties of a Frailty Index and Its Association With Mortality Risk Among Patients With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019; 71: 1297-107[3]Legge A, Kirkland S, Rockwood K, et al. Prediction of Damage Accrual in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index (SLICC-FI). Arthitis Rheumatol. Epub ahead of print 2019 Oct 21.Disclosure of Interests:Manuel F. Ugarte-Gil Grant/research support from: Jannsen, Pfizer, Jyoti Dubey: None declared, Gerald McGwin: None declared, Luis Vila: None declared, Graciela S Alarcon: None declared

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SAT0237 THE SYSTEMIC LUPUS INTERNATIONAL COLLABORATING CLINICS (SLICC) FRAILTY INDEX (SLICC-FI) PREDICTS DAMAGE ACCRUAL IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) PATIENTS. DATA FROM A LATIN AMERICAN MESTIZO COHORT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3997 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1061.1-1062

Author(s):

M. F. Ugarte-Gil ◽

R. V. Gamboa Cárdenas ◽

C. Reategui Sokolova ◽

V. Pimentel-Quiroz ◽

M. Medina Chinchon ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Latin American ◽

Lupus Erythematosus ◽

Disease Duration ◽

Negative Binomial ◽

Frailty Index ◽

Systemic Lupus ◽

Research Support ◽

Damage Accrual

Background:The Systemic Lupus International Collaborating Clinics (SLICC) Frailty Index (SLICC-FI) has been developed as a predictor of outcomes in SLE patients1-3. However, it needs to be validated in several populations.Objectives:To evaluate the SLICC-FI as a predictor of future damage accrual in systemic lupus erythematosus (SLE) patients.Methods:Patients from a single-center prevalent cohort were included. Damage accrual was defined as the increase in SLICC/American College of Rheumatology (ACR) damage index (SDI) scores between the baseline and last visits. The SLICC-FI was measured at baseline. Univariable and multivariable negative binomial regression were performed to determine the association between the baseline SLICC-FI (per 0.05 increase) and damage accrual during follow-up, adjusted for sex, age at diagnosis, socioeconomic status, disease duration, SLE Disease Activity Index 2000 (SLEDAI-2K), SDI, prednisone daily dose, antimalarial and immunosuppressive drug use at baseline, and duration of follow-up.Results:Of the 265 patients included, 248 (93.6%) were female with mean (SD) age 35.1 (13.6) years at diagnosis. At baseline, mean (SD) SLE disease duration was 7.3 (6.5) years, SDI was 1.1 (1.3) and SLEDAI-2K was 5.3 (4.6). The mean (SD) baseline SLICC-FI was 0.22 (0.05). After a mean (SD) of 5.2 (2.2) years of follow-up, the SDI increased in 126 (47.5%) patients, and the final mean (SD) SDI score was 1.7 (1.7). Higher SLICC-FI scores at baseline predicted greater damage accrual in the univariable analysis [Incidence Rate Ratio (IRR)=1.283, (CI95% 1.072-1.536); p=0.007]. The SLICC-FI remained associated with damage accrual in the multivariable model, after adjustment for possible confounders [IRR= 1.224 (CI95% 1.007-1.488); p=0.042].Conclusion:The SLICC-FI predicts damage accrual in prevalent SLE, supporting the relevance of this index in the evaluation of SLE patients. This is the first study validating the SLICC-FI in South American populationReferences:[1]Legge A, Kirkland S, Rockwood K, et al. Construction of a Frailty Index as a Novel Health Measure in Systemic Lupus Erythematosus. J Rheumatol. 2020; 47: 72-81[2]Legge A, Kirkland S, Rockwood K, et al. Evaluating the Properties of a Frailty Index and Its Association With Mortality Risk Among Patients With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019; 71: 1297-107[3]Legge A, Kirkland S, Rockwood K, et al. Prediction of Damage Accrual in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index (SLICC-FI). Arthitis Rheumatol. Epub ahead of print 2019 Oct 21.Disclosure of Interests:Manuel F. Ugarte-Gil Grant/research support from: Jannsen, Pfizer, Rocío Violeta Gamboa Cárdenas Grant/research support from: Pfizer, Cristina Reategui Sokolova: None declared, Victor Pimentel-Quiroz: None declared, Mariela Medina Chinchon: None declared, Claudia Elera-Fitzcarrald Consultant of: Tecnofarma, Jose Alfaro Lozano Speakers bureau: Lilly, Zoila Rodriguez Bellido: None declared, Cesar Pastor Asurza: None declared, Risto Perich Campos Consultant of: Pfizer, Speakers bureau: Pfizer, Graciela S Alarcon: None declared

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The Main Challenges in Systemic Lupus Erythematosus: Where Do We Stand?

Journal of Clinical Medicine ◽

10.3390/jcm10020243 ◽

2021 ◽

Vol 10 (2) ◽

pp. 243

Author(s):

Matteo Piga ◽

Laurent Arnaud

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Systemic Disease ◽

Unmet Need ◽

Clinical Manifestations ◽

New Drugs ◽

Systemic Lupus ◽

Major Step ◽

Damage Accrual

Systemic lupus erythematosus (SLE) is an immune-mediated multi-systemic disease characterized by a wide variability of clinical manifestations and a course frequently subject to unpredictable flares. Despite significant advances in the understanding of the pathophysiology and optimization of medical care, patients with SLE still have significant mortality and carry a risk of progressive organ damage accrual and reduced health-related quality of life. New tools allow earlier classification of SLE, whereas tailored early intervention and treatment strategies targeted to clinical remission or low disease activity could offer the opportunity to reduce damage, thus improving long-term outcomes. Nevertheless, the early diagnosis of SLE is still an unmet need for many patients. Further disentangling the SLE susceptibility and complex pathogenesis will allow to identify more accurate biomarkers and implement new ways to measure disease activity. This could represent a major step forward to find new trials modalities for developing new drugs, optimizing the use of currently available therapeutics and minimizing glucocorticoids. Preventing and treating comorbidities in SLE, improving the management of hard-to-treat manifestations including management of SLE during pregnancy are among the remaining major unmet needs. This review provides insights and a research agenda for the main challenges in SLE.

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Disease Damage Accrual and Low Bone Mineral Density in Female Patients with Systemic Lupus Erythematosus

Biological Research For Nursing ◽

10.1177/10998004211005550 ◽

2021 ◽

pp. 109980042110055

Author(s):

María Correa-Rodríguez ◽

Gabriela Pocovi-Gerardino ◽

José-Luis Callejas-Rubio ◽

Raquel Ríos-Fernández ◽

Blanca Rueda-Medina ◽

...

Keyword(s):

Bone Mineral Density ◽

Systemic Lupus Erythematosus ◽

Lumbar Spine ◽

Bone Mass ◽

Disease Activity ◽

Lupus Erythematosus ◽

Mineral Density ◽

Systemic Lupus ◽

Damage Accrual ◽

Disease Damage

Osteoporosis is a common comorbidity in patients with systemic lupus erythematosus (SLE), but the potential contribution of disease-associated factors to bone status in SLE is not well known because the reported risk factors from different studies differ greatly. We aimed to examine frequency of reduced bone mass in women with SLE, and determine their potential associations with disease activity, damage accrual and SLE-related clinical markers. A cross-sectional study including 121 Caucasian pre-menopausal and postmenopausal women was conducted (mean age 49.2 ± 12.4 years). The SLE Disease Activity Index (SLEDAI-2 K) and the SDI Damage Index were used to assess disease activity and disease-related damage, respectively. Bone mineral density (BMD) of the left femoral neck and lumbar spine (L2–L4) were measured by dual-energy X-ray absorptiometry. Ten patients (8.3%) had osteoporosis, 63 (52.1%) patients had osteopenia and 6.8% of women had history of previous fracture. Patients with low bone mass had a significantly higher mean SDI (1.3 ± 1.2 versus 0.7 ± 1.0 p = 0.003). T-score at lumbar spine was inversely correlated with SDI score (r = -0.222, p = 0.014) and complement C3 level ( r = −0.206, p = .024). SDI scores were significantly different between patients with osteoporosis, osteopenia, and normal BMD after adjusting for covariates ( p = .004). There is a high prevalence of low BMD in Caucasian women with SLE, and this status was associated with higher damage accrual scores, supporting that disease damage may itself be a major contributor to the low BMD. Women with SLE with organ damage require regular bone status monitoring to prevent further musculoskeletal damage.

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Longterm Outcomes and Damage Accrual in Patients with Childhood Systemic Lupus Erythematosus with Psychosis and Severe Cognitive Dysfunction

The Journal of Rheumatology ◽

10.3899/jrheum.121096 ◽

2013 ◽

Vol 40 (4) ◽

pp. 513-519 ◽

Cited By ~ 20

Author(s):

Lily Siok Hoon Lim ◽

Arlette Lefebvre ◽

Susanne Benseler ◽

Earl D. Silverman

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Cognitive Dysfunction ◽

Lupus Erythematosus ◽

Clinical Course ◽

Immunosuppressive Treatment ◽

Damage Index ◽

Response To Treatment ◽

Systemic Lupus ◽

Damage Accrual

Objective.(1) To describe the clinical course and response to treatment; and (2) to evaluate and compare damage accrual of distinct phenotypic subgroups of patients with clinically important psychiatric illness of pediatric systemic lupus erythematosus (pSLE).Methods.A single-center cohort study of patients with pSLE followed at a pediatric lupus clinic from 1985 to July 2009. Clinical course and response to treatment were studied. Remission was defined by absence of psychiatric/cognitive symptoms while receiving minimal doses of prednisone. Disease activity and damage were measured using SLE Disease Activity Index and SLE Damage Index.Results.Fifty-three children were included: 40 with psychosis and cognitive dysfunction (PSYC group) and 13 with isolated cognitive dysfunction (COG group). All received immunosuppressive treatment. Eighteen of 32 treated with azathioprine required a change to cyclophosphamide for poor response but none on cyclophosphamide required a change. The median times to remission were 72 weeks (PSYC) and 70 weeks (COG). Eight patients (7 PSYC, 1 COG) experienced flare following response/remission. New damage was noted in 50% of children at a median of 11 months: 57% of PSYC group, 31% of COG group. Persistent cognitive dysfunction was seen in 16% of PSYC patients and 15% of COG patients.Conclusion.Most patients responded to immunosuppressive treatment, although median time to remission was > 1 year. Roughly half the patients acquired a new damage item, most of which did not interfere with functional abilities. Fewer than 20% of patients developed neuropsychiatric damage. Both phenotypes of psychiatric pSLE responded equally well to current treatment.

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Mitochondrial DNA damage is associated with damage accrual and disease duration in patients with Systemic Lupus Erythematosus

Lupus ◽

10.1177/0961203314537697 ◽

2014 ◽

Vol 23 (11) ◽

pp. 1133-1141 ◽

Cited By ~ 10

Author(s):

L López-López ◽

M Nieves-Plaza ◽

M del R Castro ◽

YM Font ◽

CA Torres-Ramos ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Dna Damage ◽

Mitochondrial Dna ◽

Lupus Erythematosus ◽

Disease Duration ◽

Systemic Lupus ◽

Mitochondrial Dna Damage ◽

Damage Accrual

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The number of flares patients experience impacts on damage accrual in systemic lupus erythematosus: data from a multiethnic Latin American cohort

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2013-204620 ◽

2014 ◽

Vol 74 (6) ◽

pp. 1019-1023 ◽

Cited By ~ 42

Author(s):

Manuel F Ugarte-Gil ◽

Eduardo Acevedo-Vásquez ◽

Graciela S Alarcón ◽

Cesar A Pastor-Asurza ◽

José L Alfaro-Lozano ◽

...

Keyword(s):

Risk Factors ◽

Systemic Lupus Erythematosus ◽

Latin American ◽

Lupus Erythematosus ◽

Crossover Design ◽

Systemic Lupus ◽

Case Crossover ◽

Damage Accrual ◽

The Mean ◽

Patients Experience

PurposeTo determine the association between the number of flares systemic lupus erythematosus (SLE) patients experience and damage accrual, independently of other known risk factors.MethodsSLE patients (34 centres, nine Latin American countries) with a recent diagnosis (≤2 years) and ≥3 evaluations were studied. Disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and damage with the SLICC/ACR Damage Index (SDI). Flare was defined as an increase ≥4 points in the SLEDAI between two study visits. An ambidirectional case- crossover design was used to determine the association between the number of flares and damage accrual.Results901 patients were eligible for the study; 500 of them (55.5%) experienced at least one flare, being the mean number of flares 0.9 (SD: 1.0). 574 intervals from 251 patients were included in the case-crossover design since they have case and control intervals, whereas, the remaining patients did not. Their mean age at diagnosis was 27.9 years (SD: 11.1), 213 (84.9%) were women. The mean baseline SDI and SLEDAI were 1.3 (1.3) and 13.6 (8.1), respectively. Other features were comparable to those of the entire sample. After adjusting for possible confounding variables, the number of flares, regardless of their severity, was associated with damage accrual (SDI) OR 2.05, 95% CI 1.43 to 2.94, p<0.001 (OR 2.62, 95% CI 1.31 to 5.24, p=0.006 for severe and OR 1.91, 95% CI 1.28 to 2.83, p=0.001for mild-moderate).ConclusionsThe number of flares patients experience, regardless of their severity, increases the risk of damage accrual, independently of other known risk factors.

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The Early Protective Effect of Hydroxychloroquine on the Risk of Cumulative Damage in Patients with Systemic Lupus Erythematosus

The Journal of Rheumatology ◽

10.3899/jrheum.120572 ◽

2013 ◽

Vol 40 (6) ◽

pp. 831-841 ◽

Cited By ~ 60

Author(s):

Pooneh S. Akhavan ◽

Jiandong Su ◽

Wendy Lou ◽

Dafna D. Gladman ◽

Murray B. Urowitz ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Conditional Logistic Regression ◽

Univariate Analysis ◽

Damage Index ◽

Immunosuppressive Drugs ◽

Clinical Effects ◽

Systemic Lupus ◽

Steroid Dose ◽

Damage Accrual

Objective.To assess whether hydroxychloroquine (HCQ) prevents early damage in patients with systemic lupus erythematosus (SLE).Methods.We updated an existing systematic review of literature on clinical effects of HCQ in patients with SLE. We conducted a nested case-control study embedded in an inception cohort of patients with SLE. Systemic Lupus International Collaborating Clinics Damage Index (SDI) at 3 years was considered as our primary outcome. Patients with SDI > 0 at 3 years were considered cases and patients with SDI = 0 were controls. Cases and controls were first compared by univariate analysis. Then conditional logistic regression models adjusting for potential confounders were done to study the effect of HCQ on damage accrual.Results.Included in the analysis were 481 patients who had 3 or more years of followup. Out of this cohort, we could match 151 cases with 151 controls. Univariate analysis identified age, the use of any immunosuppressive drugs, HCQ, and cumulative dose of steroids as significant covariates associated with damage accrual. In multivariate analysis, the use of HCQ remained significantly associated with less damage (OR 0.34, 95% CI 0.132–0.867), while age (OR 1.05, 95% CI 1.027–1.078) and a variable combining SLE activity and steroid dose (OR 1.73, 95% CI 1.306–2.295) were associated with damage at 3 years.Conclusion.We demonstrated that HCQ use was associated with less damage at 3 years after diagnosis of SLE when attention was given and adjustment done for disease activity and steroid dose, duration of disease, and calendar year of diagnosis.

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Seventy years after Hench’s Nobel prize: revisiting the use of glucocorticoids in systemic lupus erythematosus

Lupus ◽

10.1177/0961203320930099 ◽

2020 ◽

Vol 29 (10) ◽

pp. 1155-1167 ◽

Cited By ~ 3

Author(s):

Guillermo Ruiz-Irastorza ◽

Amaia Ugarte ◽

Ioana Ruiz-Arruza ◽

Munther Khamashta

Keyword(s):

Systemic Lupus Erythematosus ◽

Nobel Prize ◽

Lupus Erythematosus ◽

Therapeutic Use ◽

High Dose ◽

Dependent Manner ◽

Systemic Lupus ◽

Early Therapy ◽

Damage Accrual

In 1950, Hench, Kendall and Reichstein were awarded with the Nobel Prize in Physiology and Medicine for the isolation and first therapeutic use of glucocorticoids. Since then, they have become one of the main agents in the treatment of systemic lupus erythematosus (SLE). The use of high-dose oral glucocorticoids (usually 1 mg/kg/day of prednisone equivalent) have become the rule for treating moderate to severe lupus activity. In addition, tapering schemes have not been well defined, all this leading to prolonged exposures to potentially damaging amounts of glucocorticoids. Several studies have shown that glucocorticoids are a major cause of toxicity in SLE in a dose-dependent manner, with prolonged doses greater than 7.5 mg/day being associated with damage accrual. Thus, there is an urgent need for different therapeutic schedules that can achieve a rapid and durable control of lupus activity while reducing the many unwanted effects of glucocorticoids. Recent data show that pulses of methyl-prednisolone are an effective first-line therapy to treat lupus flares (not only severe ones) without major short or long-term toxicity and allowing a reduction in oral prednisone doses. Universal use of hydroxychloroquine – always recommended, infrequently accomplished – and early therapy with immunosuppressive drugs also help control SLE and reduce prednisone load. Results from observational studies confirm the more rapid achievement of remission and the reduction of long-term damage using these combination schedules with reduced prednisone doses. Seventy years after their first therapeutic use, we are learning to use glucocorticoids in a more efficient and safe manner.

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