Construction and Validation of a Frailty Index As a Novel Health Measure in Systemic Lupus Erythematosus

Alexandra Legge¹, Susan Kirkland², Kenneth Rockwood³, Pantelis Andreou², Sang-Cheol Bae⁴, Caroline Gordon⁵, Juanita Romero-Díaz⁶, Jorge Sanchez-Guerrero⁷, Daniel J. Wallace⁸, Sasha Bernatsky⁹, Ann E. Clarke¹⁰, Joan T. Merrill¹¹, Ellen M. Ginzler¹², Paul R. Fortin¹³, Dafna D Gladman¹⁴, Murray Urowitz⁷, Ian N. Bruce¹⁵, David A. Isenberg¹⁶, Anisur Rahman¹⁷, Graciela S. Alarcón¹⁸, Michelle Petri¹⁹, Munther A Khamashta²⁰, Mary Dooley²¹, Rosalind Ramsey-Goldman²², Susan Manzi²³, Kristján Steinsson²⁴, Asad A Zoma²⁵, Cynthia Aranow²⁶, Meggan Mackay²⁶, Guillermo Ruiz-Irastorza²⁷, S. Sam Lim²⁸, Murat Inanc²⁹, Ronald F van Vollenhoven³⁰, Andreas Jönsen³¹, Ola Nived³¹, Manuel Ramos-Casals³², Diane L. Kamen³³, Kenneth C. Kalunian³⁴, Søren Jacobsen³⁵, Christine A. Peschken³⁶, Anca Askanase³⁷ and John G. Hanly³⁸, ¹Department of Medicine, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, NS, Canada, ²Department of Community Health & Epidemiology, Dalhousie University, Halifax, NS, Canada, ³Department of Medicine, Division of Geriatric Medicine, Dalhousie University, Halifax, NS, Canada, ⁴Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, Republic of (South), ⁵Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom, ⁶Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico, ⁷University of Toronto Lupus Research Program, Toronto Western Hospital, Toronto, ON, Canada, ⁸Cedars-Sinai/David Geffen School of Medicine at UCLA, Los Angeles, CA, ⁹Divisions of Rheumatology and Clinical Epidemiology, The Research Institute of the McGill University Health Centre, Montreal, QC, Canada, ¹⁰Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada, ¹¹University of Oklahoma Health Sciences Center, Oklahoma City, OK, ¹²Rheumatology, SUNY Downstate Medical Center, Brooklyn, NY, ¹³Medicine, CHU de Québec - University of Laval, Quebec, QC, Canada, ¹⁴Krembil Research Institute, Toronto Western Hospital, Toronto, ON, Canada, ¹⁵Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester, United Kingdom, ¹⁶University College London, London, United Kingdom, ¹⁷Rayne Institute, University College London, London, United Kingdom, ¹⁸University of Alabama at Birmingham, Birmingham, AL, ¹⁹Johns Hopkins University School of Medicine, Baltimore, MD, ²⁰Graham Hughes Lupus Research Laboratory, The Rayne Institute, London, United Kingdom, ²¹Dooley Rheumatology, Chapel Hill Doctors, Chapel Hill, NC, ²²FSM, Northwestern University, Chicago, IL, ²³Autoimmunity Institute and Medicine Institute, Allegheny Health Network, Pittsburgh, PA, ²⁴Rheumatology, Univ. Hospital, Reykjavik, Iceland, ²⁵Lanarkshire Center for Rheumatology, Hairmyres Hospital, East Kilbride, East Kilbride, Scotland, United Kingdom, ²⁶The Feinstein Institute for Medical Research, Manhasset, NY, ²⁷Autoimmune Diseases Research Unit, Department of Internal Medicine, BioCruces Health Research Institute, Hospital Universitario Cruces, University of the Basque Country, Barakaldo, Spain, ²⁸Emory University School of Medicine, Atlanta, GA, ²⁹Department of Internal Medicine, Division of Rheumatology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey, ³⁰Unit for clinical therapy research (ClinTRID), Karolinska Institute, Stockholm, Sweden, ³¹Rheumatology, Lund University, Department of Clinical Sciences, Lund, Sweden, ³²Laboratory of Systemic Autoimmune Diseases “Josep Font”, CELLEX, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Systemic Autoimmune Diseases, ICMID, Hospital Clinic, Barcelona, Spain, Barcelona, Spain, ³³Medicine/Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC, ³⁴Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, La Jolla, CA, ³⁵Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, ³⁶RR 149G, University of Manitoba, Winnipeg, MB, Canada, ³⁷Rheumatology, Columbia University, College of Physician and Surgeons, New York, NY, ³⁸Division of Rheumatology, Department of Medicine and Department of Pathology, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, NS, Canada

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: outcome measures and systemic lupus erythematosus (SLE)

Session Information

Date: Monday, October 22, 2018

Title: Systemic Lupus Erythematosus – Clinical Poster II: Biomarkers and Outcomes

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Clinical outcomes in SLE are challenging to predict. In non-SLE populations, susceptibility to adverse outcomes has been measured using a frailty index (FI), which quantifies vulnerability via the accumulation of health deficits. Using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort, we constructed and validated a frailty index for patients with SLE.

Methods: Patients fulfilling ≥4 ACR classification criteria for SLE were recruited within 15 months of diagnosis and were assessed annually for medication use, comorbidities, disease activity (SLEDAI-2K), organ damage [SLICC/ACR Damage Index (SDI)], health-related quality of life [Short-Form 36 (SF-36)] and other measures.

For our analysis, the baseline visit was defined as the first at which both SDI and SF-36 data were available. From this baseline dataset, health deficits were identified for inclusion in the SLICC frailty index (SLICC-FI). Using standard criteria, a health deficit was defined as any symptom, disease process, functional impairment, or laboratory abnormality that is: (i) acquired, (ii) associated with increasing age, (iii) associated with adverse outcomes, (iv) present in ≥1% and ≤80% of patients, and (v) missing values for <5% of patients. Once selected, the health deficits were used to calculate a baseline SLICC-FI score for each patient.

To assess validity, we estimated correlations of the SLICC-FI with existing SLE instruments, including the SDI and the SLEDAI-2K. Multivariable Cox regression was used to estimate associations between baseline SLICC-FI values and mortality risk, adjusting for relevant demographic and clinical variables.

Results: 1682 SLE patients (92.1% of the cohort) were eligible for inclusion and were predominantly female (89%) with mean (SD) age 35.7 (13.4) years and mean (SD) disease duration 18.8 (15.7) months at baseline. Of 222 candidate variables, 48 met the required criteria for inclusion as health deficits in the SLICC-FI. These included items related to organ damage, disease activity, comorbidities, and functional status. The mean (SD) baseline SLICC-FI score was 0.17 (0.08) with a range from 0 to 0.51. At baseline, SLICC-FI values were weakly correlated with both SDI (r=0.262; p<0.0001) and SLEDAI-2K (r=0.227; p<0.0001) scores. These correlations persisted after removing overlapping SDI and SLEDAI-2K items from the SLICC-FI.

Sixty-six deaths occurred during a mean (SD) follow-up of 6.7 (4.0) years. Higher baseline SLICC-FI values (per 0.05 increase) were associated with increased mortality risk (Hazard Ratio [HR] 1.59; 95% CI 1.35-1.87), after adjusting for age, sex, baseline steroid use, race/ethnicity, geographic region, and baseline SDI scores. The association between baseline SLICC-FI scores and mortality risk persisted when damage items were omitted from the SLICC-FI (HR 1.37; 95% CI 1.22-1.53) and when a subgroup of patients without baseline organ damage (SDI=0) was analyzed (HR 1.47; 95% CI 1.18-1.83).

Conclusion: The SLICC-FI is a relevant health measure in SLE. It predicts future mortality risk independent of the SDI and is a potentially valuable tool for identifying SLE patients who are most vulnerable to adverse outcomes.

Disclosure: A. Legge, None; S. Kirkland, None; K. Rockwood, None; P. Andreou, None; S. C. Bae, None; C. Gordon, None; J. Romero-Díaz, None; J. Sanchez-Guerrero, None; D. J. Wallace, None; S. Bernatsky, None; A. E. Clarke, None; J. T. Merrill, None; E. M. Ginzler, None; P. R. Fortin, None; D. D. Gladman, None; M. Urowitz, None; I. N. Bruce, None; D. A. Isenberg, None; A. Rahman, None; G. S. Alarcón, None; M. Petri, None; M. A. Khamashta, None; M. Dooley, None; R. Ramsey-Goldman, None; S. Manzi, None; K. Steinsson, None; A. A. Zoma, None; C. Aranow, None; M. Mackay, None; G. Ruiz-Irastorza, None; S. S. Lim, None; M. Inanc, None; R. F. van Vollenhoven, None; A. Jönsen, None; O. Nived, None; M. Ramos-Casals, None; D. L. Kamen, None; K. C. Kalunian, None; S. Jacobsen, None; C. A. Peschken, None; A. Askanase, None; J. G. Hanly, None.

To cite this abstract in AMA style:

Legge A, Kirkland S, Rockwood K, Andreou P, Bae SC, Gordon C, Romero-Díaz J, Sanchez-Guerrero J, Wallace DJ, Bernatsky S, Clarke AE, Merrill JT, Ginzler EM, Fortin PR, Gladman DD, Urowitz M, Bruce IN, Isenberg DA, Rahman A, Alarcón GS, Petri M, Khamashta MA, Dooley M, Ramsey-Goldman R, Manzi S, Steinsson K, Zoma AA, Aranow C, Mackay M, Ruiz-Irastorza G, Lim SS, Inanc M, van Vollenhoven RF, Jönsen A, Nived O, Ramos-Casals M, Kamen DL, Kalunian KC, Jacobsen S, Peschken CA, Askanase A, Hanly JG. Construction and Validation of a Frailty Index As a Novel Health Measure in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/construction-and-validation-of-a-frailty-index-as-a-novel-health-measure-in-systemic-lupus-erythematosus/. Accessed .

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