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Abstract Number: 2562

Glucocorticosteroid Usage and Major Organ Damage in Patients with Systemic Lupus Erythematosus – Meta-analyses of Observational Studies Published Between 1979 and 2018

Anselm Mak1, Mike W.L.- Cheung 1, Wai Yee Joanna Leong 2, Bhushan Dharmadhikari 3, Nien Yee Kow 3, Michelle Petri 4, Susan Manzi 5, Ann Clarke 6, Cynthia Aranow 7, Laurent Arnaud 8, Anca Askanase 9, Sang-Cheol Bae 10, Sasha Bernatsky 11, Ian Bruce 12, Jill Buyon 13, W. Winn Chatham 14, Nathalie Costedoat-Chalumeau 15, MA Dooley 16, Paul Fortin 17, Ellen M Ginzler 18, Dafna Gladman 19, Caroline Gordon 20, John G Hanly 21, Murat Inanc 22, David A Isenberg 23, Soren Jacobsen 24, Judith James 25, Andreas Jönsen 26, Kenneth C Kalunian 27, Diane Kamen 28, S Sam Lim 29, Eric Morand 30, Christine Peschken 31, Bernardo A. Pons-Estel 32, Anisur Rahman 33, Rosalind Ramsey-Goldman 34, Juanita Romero-Diaz 35, Guillermo Ruiz-Irastorza 36, Jorge Sanchez-Guerrero 37, Kristjan Steinsson 38, Elisabet Svenungsson 39, Murray Urowitz 40, Ronald van Vollenhoven 41, Evelyne Vinet 42, Alexandre Voskuyl 43, Daniel J Wallace 44 and Graciela Alarcón 45, 1National University of Singapore, Singapore, Singapore, 2Changi General Hospital, Singapore, Singapore, 3National University of Singapore, Singapore, 4Johns Hopkins University School of Medicine, Baltimore, MD, 5Allegheny Health Network, Pittsburg, PA, 6University of Calgary, Calgary, AB, Canada, 7Feinstein Institute for Medical Research, Manhasset, NY, 8Service de Rhumatologie, Centre National de Référence des Maladies Autoimmunes Systemiques Rares (RESO), Hôpitaux Universitaires de Strasbourg, Strasbourg, France, Strasbourg, France, 9Columbia University Medical Center, New York, NY, 10Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea, 11Research Institute of the McGill University Health Centre, Montreal, QC, Canada, 12University of Manchester, Manchester, United Kingdom, Manchester, England, United Kingdom, 13NYU School of Medicine, New York, 14University of Alabama Medical Center, Birmingham, AL, 15Cochin University Hospital, Paris, France, 16UnC Kidney Centre, Chapel Hill, NC, 17Division 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, 18State University of New York Downstate Medical Center, Brooklyn, NY, 19Toronto Western Hospital, Toronto, Canada, Toronto, ON, Canada, 20University of Birmingham, Birmingham, United Kingdom, 21Dalhousie University, Halifax, NS, Canada, 22Istanbul University, Istanbul Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Istanbul, Turkey, 23Centre for Rheumatology, London, United Kingdom, 24Copenhagen Lupus and Vasculitis Clinic, Copenhagen, Denmark, 25Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 26Lund University, Lund, Sweden, 27UC San Diego School of Medicine, LaJolla, CA, 28Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA., Charleston, SC, 29Emory University, Atlanta, GA, 30Monash University, Melbourne, Victoria, Australia, 31University of Manitoba, Winnipeg, Canada, 32Centro Regional de Enfermedades Autoinmunes y Reumáticas (CREAR), Grupo Oroño, Rosario, Rosario, Argentina, 33University College London, London, United Kingdom, 34Northwestern University, Chicago, IL, 35Instituto Nacional de Ciencias Medicas y Nutricion Salvador, Zubiran Vasco de Quiroga, Mexico City, Mexico, 36Autoimmune Diseases Unit, Hospital Universitario Cruces, Barakaldo, Spain, Barakaldo, Spain, 37Toronto Western Hospital, Toronto, ON, Canada, 38Landspitali, University Hospital, Reykjavik, Iceland, 39Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden, 40University Health Network, University of Toronto, Toronto, ON, Canada, 41Amsterdam Rheumatology and Immunology Center ARC, Amsterdam, the Netherlands, Amsterdam, Netherlands, 42McGill University Health Centre, Montreal, QC, Canada, 43Amsterdam Rheumatology and Immunology Center, Amsterdam, Netherlands, 44Cedars-Sinai Medical Centre, Beverly Hills, CA, 45University of Alabama at Birmingham, Birmingham

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: glucocorticoids and meta-analysis, Systemic lupus erythematosus (SLE)

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Session Information

Date: Tuesday, November 12, 2019

Session Title: SLE – Clinical Poster III: Treatment

Session Type: Poster Session (Tuesday)

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

Background/Purpose: The impact of glucocorticoid (GC) use on major organ damage in SLE patients has not been formally studied by amalgamating the relevant data published in the literature over the past 40 years. We aimed to study the association between GC use and the occurrence of major organ damage in SLE patients by performing meta-analyses of observational studies published between 1970 and December 2018.

Methods: Literature search on PubMed (from 1966 to December 2018) for prevalence and longitudinal studies which reported GC exposure (proportion of GC users in the cohort [%GC use] and/or GC use in defined doses) and the occurrence (prevalence/incidence) of major organ damage in SLE patients using the keywords “cataract”, “cerebrovascular” (CVA), “stroke”, “cardiovascular” (CVS), “angina”, “myocardial infarction” (MI), “coronary artery bypass”, “osteoporosis”,  “avascular necrosis” (AVN) and “osteonecrosis” in respective combinations with “lupus” was conducted. Studies with sample size < 50 and observation duration < 12 months were excluded. The logit of the proportion of patients with disease damage was modelled as a random effect in the meta-analysis, which was employed to study the association between the proportion of patients with organ damage and variables of GC use (mean daily [mg/day] and cumulative [gm] prednisone [PDN] doses and %GC use). A 2-stage estimation of the random-effects logistic regression models was used with restricted maximum likelihood estimation. Univariate associations between organ damage and moderators were examined for statistical significance, and variables related to GC use were adjusted for SLE disease duration in multivariate models if their univariate P values were < 0.2.

Results: Out of 8,882 publications screened, 212 articles involving 205,619 SLE patients were eligible for the meta-analyses (Figure 1), of which 97 were prevalence and 115 were longitudinal studies. Univariate analyses of prevalence studies revealed that mean daily PDN dose (odds ratio [OR]=1.10, p=0.007) and lower proportion of female in the cohort (OR=0.002, p=0.002) were associated with the prevalence of overall CVS events. Mean daily PDN dose (OR=1.52, p< 0.001) and %GC use (OR=2,255.2, p< 0.001) were associated with the prevalence of AVN. A significant association between cumulative PDN dose and prevalence of CVA was found after multivariate adjustment for SLE disease duration (OR=1.07, p=0.017). In longitudinal studies, a significant association was identified between cumulative PDN dose and incidence of cataracts after adjustment for SLE disease duration (OR=1.04, p=0.013). While the incidence of MI in SLE patients has dropped over the past 40 years (OR=0.94, p=0.002), it was associated with % GC use after adjustment for SLE disease duration (OR=8.18, p=0.012). Interestingly, significant univariate associations were found between antimalarial use and lower prevalence of MI (OR=0.05, p=0.002) and lower incidence of CVA (OR=0.20, p=0.032).

Conclusion: Independent of SLE disease duration, cumulative PDN dose was associated with higher prevalence of CVA and incidence of cataracts, and higher incidence of MI was associated with overall GC use.

Figure 1. Result of literature search


Disclosure: A. Mak, None; M. Cheung, None; W. Leong, None; B. Dharmadhikari, None; N. Kow, None; M. Petri, Eli Lilly and Company, 5, Exagen, 2, 5; S. Manzi, Allegheny Health Network, 3, AstraZeneca, 2, 5; A. Clarke, AstraZeneca/MedImmune, 5, Bristol-Myers Squibb, 5, Exagen Diagnostics, 5; C. Aranow, EMD Serrono, 2, GlaxoSmithKline, 2, Janssen, 2, Takeda, 2, UCB, Inc, 2, Xencor, 2; L. Arnaud, None; A. Askanase, None; S. Bae, None; S. Bernatsky, None; 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; J. Buyon, Bristol Myers Squibb, 5, Exagen Diagnostics, 2; W. Chatham, AstraZeneca, 2; N. Costedoat-Chalumeau, None; M. Dooley, None; P. Fortin, None; E. Ginzler, Ablynx, 5, Aurinia, 2, Genentech, 2, GlaxoSmithKline, 2, Guidepoint Global Gerson Lerman Group, 5, Janssen, 5; D. Gladman, AbbVie, 2, 5, Amgen, 2, 5, BMS, 5, Celgene, 2, 5, Eli Lilly, 2, 5, Galapagos, 5, Galapagos NV, 5, Gilead, 5, GSI, 5, Janssen, 5, Janssen Research & Development, LLC, 2, Novartis, 2, 5, Pfizer, 2, 5, UCB, 2, 5; 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. Hanly, None; M. Inanc, None; D. Isenberg, None; S. Jacobsen, None; J. James, Abbvie, 5, Janssen, 5, Progentec, 2, Progentec Diagnostics, Inc., 2, Xencor, 2, Xencor, Inc., 2; A. Jönsen, 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; D. Kamen, None; S. Lim, None; E. Morand, AstraZeneca, 2, 5, 8, Bristol Myers Squibb, 2, Eli Lilly, 5, Janssen, 2, 5, Merck Serono, 2, 5, UCB, 2; C. Peschken, Astra Zeneca, 2, Celgene, 2, Janssen, 2; B. Pons-Estel, None; A. Rahman, None; R. Ramsey-Goldman, Exagen, 2; J. Romero-Diaz, None; G. Ruiz-Irastorza, None; J. Sanchez-Guerrero, None; K. Steinsson, None; E. Svenungsson, None; M. Urowitz, Janssen Research & Development, LLC, 2, UCB Pharma, 9; R. van Vollenhoven, AbbVie, 2, 9, Arthrogen, 2, AstraZeneca, 9, Biotest, 9, BMS, 2, 9, Celgene, 9, GSK, 2, 9, Janssen, 9, Lilly, 2, 9, medac, 9, Merck, 9, Novartis, 9, Pfizer, 2, 9, Roche, 9, UCB, 2, 9; E. Vinet, None; A. Voskuyl, None; D. Wallace, None; G. Alarcón, None.

To cite this abstract in AMA style:

Mak A, Cheung M, Leong W, Dharmadhikari B, Kow N, Petri M, Manzi S, Clarke A, Aranow C, Arnaud L, Askanase A, Bae S, Bernatsky S, Bruce I, Buyon J, Chatham W, Costedoat-Chalumeau N, Dooley M, Fortin P, Ginzler E, Gladman D, Gordon C, Hanly J, Inanc M, Isenberg D, Jacobsen S, James J, Jönsen A, Kalunian K, Kamen D, Lim S, Morand E, Peschken C, Pons-Estel B, Rahman A, Ramsey-Goldman R, Romero-Diaz J, Ruiz-Irastorza G, Sanchez-Guerrero J, Steinsson K, Svenungsson E, Urowitz M, van Vollenhoven R, Vinet E, Voskuyl A, Wallace D, Alarcón G. Glucocorticosteroid Usage and Major Organ Damage in Patients with Systemic Lupus Erythematosus – Meta-analyses of Observational Studies Published Between 1979 and 2018 [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/glucocorticosteroid-usage-and-major-organ-damage-in-patients-with-systemic-lupus-erythematosus-meta-analyses-of-observational-studies-published-between-1979-and-2018/. Accessed April 13, 2021.
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