Prediction of Organ Damage Accrual in Systemic Lupus Erythematosus Using a Frailty Index

Alexandra Legge¹, Susan Kirkland ¹, Kenneth Rockwood ¹, Pantelis Andreou ¹, Sang-Cheol Bae ², Caroline Gordon ³, Juanita Romero-Diaz ⁴, Jorge Sanchez-Guerrero ⁵, Daniel J Wallace ⁶, Sasha Bernatsky ⁷, Ann E Clarke ⁸, Joan Merrill ⁹, Ellen M Ginzler ¹⁰, Paul Fortin ¹¹, Dafna Gladman ¹², Murray Urowitz ¹³, Ian Bruce ¹⁴, David A Isenberg ¹⁵, Anisur Rahman ¹⁶, Graciela Alarcón ¹⁷, Michelle Petri ¹⁸, Munther A Khamashta ¹⁹, MA Dooley ²⁰, Rosalind Ramsey-Goldman ²¹, Susan Manzi ²², Kristjan Steinsson ²³, Asad A Zoma ²⁴, Cynthia Aranow ²⁵, Meggan Mackay ²⁶, Guillermo Ruiz-Irastorza ²⁷, S Sam Lim ²⁸, Murat Inanc ²⁹, Ronald F Van Vollenhoven ³⁰, Andreas Jönsen ³¹, Ola Nived ³¹, Manuel Ramos-Casals ³², Diane Kamen ³³, Kenneth C Kalunian ³⁴, Soren Jacobsen ³⁵, Christine Peschken ³⁶, Anca Askanase ³⁷ and John G Hanly ¹, ¹Dalhousie University, Halifax, NS, Canada, ²Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea, ³University of Birmingham, Birmingham, United Kingdom, ⁴Instituto Nacional de Ciencias Medicas y Nutricion Salvador, Zubiran Vasco de Quiroga, Mexico City, Mexico, ⁵Toronto Western Hospital, Toronto, ON, Canada, ⁶Cedars-Sinai Medical Centre, Beverly Hills, CA, ⁷Research Institute of the McGill University Health Centre, Montreal, QC, Canada, ⁸University of Calgary, Calgary, AB, Canada, ⁹Oklahoma Medical Research Foundation, Oklahoma City, ¹⁰State University of New York Downstate Medical Center, Brooklyn, NY, ¹¹Division de Rhumatologie, Département de Médecine, CHU de Québec – Université Laval, Axe maladies infectieuses et inflammatoires, Centre de recherche du CHU de Québec – Université Laval, Canada, Quebec, QC, Canada, ¹²University of Toronto, Toronto, ON, Canada, ¹³University Health Network, University of Toronto, Toronto, ON, Canada, ¹⁴University of Manchester, Manchester, United Kingdom, Manchester, England, United Kingdom, ¹⁵Centre for Rheumatology, London, United Kingdom, ¹⁶University College London, London, United Kingdom, ¹⁷University of Alabama at Birmingham, Birmingham, ¹⁸Johns Hopkins University School of Medicine, Baltimore, MD, ¹⁹King's College London School of Medicine, London, United Kingdom, ²⁰UnC Kidney Centre, Chapel Hill, NC, ²¹Northwestern University, Chicago, IL, ²²Allegheny Health Network, Pittsburg, PA, ²³Landspitali, University Hospital, Reykjavik, Iceland, ²⁴University of Glasgow, East Kilbride, United Kingdom, ²⁵Feinstein Institute for Medical Research, Manhasset, NY, ²⁶Feinstein Institute for Medical Research, New York, ²⁷Unidad de Enfermedades Autoinmunes, BioCruces Health Research Institute, Barakaldo, Spain, ²⁸Emory University, Atlanta, GA, ²⁹Istanbul University, Istanbul Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Istanbul, Turkey, ³⁰Amsterdam Rheumatology & Immunology Center, Amsterdam, Netherlands, ³¹Lund University, Lund, Sweden, ³²Department of Autoimmune Diseases, ICMiD. Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX. Department of Medicine, University of Barcelona, Hospital Clínic, Barcelona, Spain., Barcelona, Spain, ³³Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA., Charleston, SC, ³⁴UC San Diego School of Medicine, LaJolla, CA, ³⁵Copenhagen Lupus and Vasculitis Clinic, Copenhagen, Denmark, ³⁶University of Manitoba, Winnipeg, Canada, ³⁷Columbia University Medical Center, New York, NY

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: outcome measures and cohort, Systemic lupus erythematosus (SLE)

Session Information

Date: Monday, November 11, 2019

Title: SLE – Clinical Poster II: Comorbidities

Session Type: Poster Session (Monday)

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

Background/Purpose: We previously constructed a frailty index (FI) as a measure of susceptibility to adverse outcomes among patients with systemic lupus erythematosus (SLE). In this work, higher baseline FI values were associated with increased mortality risk during follow-up. However, the association with other clinically important health outcomes has not been described. Therefore, the objective of the current study was to estimate the association of baseline FI values with the risk of subsequent organ damage accrual in a large, prospective, international, inception cohort of SLE patients.

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 as both instruments, in addition to other variables, were used to generate the baseline FI scores. We determined organ damage accrual during follow-up by subtracting the baseline SDI score from the SDI score at the final study visit. Any change in SDI ≥ 1 defined damage accrual.

Multivariable negative binomial regression was used to estimate the association between baseline FI values and the rate of change in SDI scores per patient-year of follow-up, adjusting for relevant demographic and clinical characteristics. Model fit was evaluated using likelihood ratio (LR) tests and Akaike information criterion (AIC) values.

Results: The 1,549 SLE patients (84.8% of the cohort) eligible for this analysis were mostly female (88.7%) with mean (SD) age 35.7 (13.3) years and median (IQR) disease duration 1.2 (0.9-1.5) years at baseline. Mean (SD) baseline FI score was 0.17 (0.08) with a range from 0 to 0.51.

Over a mean (SD) follow-up of 7.2 (3.7) years, 653 patients (42.2%) had an increase in SDI score. Higher baseline FI values (per 0.05 increment) were associated with higher rates of change in SDI scores during follow-up (Incidence Rate Ratio [IRR] 1.19; 95% CI 1.13-1.25), after adjusting for age, sex, ethnicity/region, post-secondary education, baseline SLEDAI-2K, baseline SDI, and baseline use of corticosteroids, antimalarials, and immunosuppressives.

The addition of the baseline FI to the multivariable model was associated with significant improvement in model fit (LR test statistic 40.49 [p< 0.001]) and relative predictive quality (change in AIC = 3563.60 – 3602.09 = -38.49). Furthermore, the association between the baseline FI and subsequent damage accrual persisted when overlapping damage items were omitted from the FI (IRR 1.12; 95% CI 1.08-1.16) and when the analysis was restricted to the subgroup of patients without organ damage (SDI=0) at the baseline visit (IRR 1.21; 95% CI 1.14-1.30).

Conclusion: Frailty, measured using an FI, predicts organ damage accrual among SLE patients and provides added prognostic value when considered in addition to existing SLE measures. This further supports the FI as a valid and robust health measure in SLE.

Disclosure: A. Legge, None; S. Kirkland, None; K. Rockwood, None; P. Andreou, None; S. Bae, None; C. Gordon, Bristol-Myers Squibb, 5, 8, Centers for Disease Control and Prevention, 5, Eli Lilly, 5, 8, EMD Serono, 5, EMD Serono, UCB, 5, GlaxoSmithKline, 5, 8, Merck Serono, 5, 8, UCB, 2, 5, 8, Versus Arthritis/GSK, 2; J. Romero-Diaz, None; J. Sanchez-Guerrero, None; D. Wallace, None; S. Bernatsky, None; A. Clarke, AstraZeneca/MedImmune, 5, Bristol-Myers Squibb, 5, Exagen Diagnostics, 5; J. Merrill, Xencor, 2; E. Ginzler, Ablynx, 5, Aurinia, 2, Genentech, 2, GlaxoSmithKline, 2, Guidepoint Global Gerson Lerman Group, 5, Janssen, 5; P. Fortin, None; D. Gladman, AbbVie, 2, 5, AbbVie, Amgen, BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB, 2, 5, Amgen, 2, 5, BMS, 5, Celgene, 2, 5, Eli Lilly, 2, 5, Galapagos, 5, Gilead, 5, GlaxoSmithKline, 5, 8, Janssen, 5, Novartis, 2, 5, Pfizer Inc, 2, 5, UCB, 2, 5; M. Urowitz, Janssen Research & Development, LLC, 2, UCB Pharma, 9; I. Bruce, Astra Zenica, 5, AstraZeneca, 5, Eli Lilly, 5, 8, Genzyme Sanofi, 2, GlaxoSmithKline, 2, 5, 8, GSK, 2, 5, 8, ILTOO, 5, Iltoo, 5, MedImmune, 5, 8, Medimmune, 5, Merck Serono, 5, 8, Merk Serono, 5, Roche, 5, 8, Sanofi Genzyme, 2, UCB, 2, 5, 8, UCB Pharma, 5, 8; D. Isenberg, None; A. Rahman, None; G. Alarcón, None; M. Petri, Eli Lilly and Company, 5, Exagen, 2, 5; M. Khamashta, None; M. Dooley, None; R. Ramsey-Goldman, Exagen, 2; S. Manzi, Allegheny Health Network, 3, AstraZeneca, 2, 5; K. Steinsson, None; A. Zoma, None; C. Aranow, EMD Serrono, 2, GlaxoSmithKline, 2, Janssen, 2, Takeda, 2, UCB, Inc, 2, Xencor, 2; M. Mackay, None; G. Ruiz-Irastorza, None; S. Lim, None; M. Inanc, None; R. Van Vollenhoven, Abbvie, 5, 8, Astra-Zeneca, 5, 8, Biotest, 5, 8, BMS, 2, 5, 8, Celgene, 5, 8, GSK, 2, 5, 8, Janssen, 5, 8, Lilly, 2, 5, 8, Novartis, 5, 8, Pfizer, 5, 8, Roche, 5, 8, UCB, 2, 5, 8; A. Jönsen, None; O. Nived, None; M. Ramos-Casals, None; D. Kamen, None; K. Kalunian, Ablynx, 2, Anthera, 5, Bristol-Myers Squibb, 2, 5, Eli Lilly, 5, Equillium, 5, Exagen Diagnostics, 5, Genentech, 5, Human Genome Sciences/GlaxoSmithKline, 2, Kyowa Hakko Kirin, 2, Pfizer, 2, Takeda, 2, UCB, 2; S. Jacobsen, None; C. Peschken, Astra Zeneca, 2, Celgene, 2, Janssen, 2; A. Askanase, None; J. Hanly, None.

To cite this abstract in AMA style:

Legge A, Kirkland S, Rockwood K, Andreou P, Bae S, Gordon C, Romero-Diaz J, Sanchez-Guerrero J, Wallace D, Bernatsky S, Clarke A, Merrill J, Ginzler E, Fortin P, Gladman D, Urowitz M, Bruce I, Isenberg D, Rahman A, Alarcón G, Petri M, Khamashta M, Dooley M, Ramsey-Goldman R, Manzi S, Steinsson K, Zoma A, Aranow C, Mackay M, Ruiz-Irastorza G, Lim S, Inanc M, Van Vollenhoven R, Jönsen A, Nived O, Ramos-Casals M, Kamen D, Kalunian K, Jacobsen S, Peschken C, Askanase A, Hanly J. Prediction of Organ Damage Accrual in Systemic Lupus Erythematosus Using a Frailty Index [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/prediction-of-organ-damage-accrual-in-systemic-lupus-erythematosus-using-a-frailty-index/. Accessed .

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