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)

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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