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Abstract Number: 2785

Cancer Risk in a Large Inception SLE Cohort: Effects of Age, Smoking, and Medications

Sasha Bernatsky1, Rosalind Ramsey-Goldman 2, Murray Urowitz 3, John Hanly 4, Caroline Gordon 5, Michelle Petri 6, Ellen M Ginzler 7, Daniel J Wallace 8, Sang-Cheol Bae 9, Juanita Romero-Diaz 10, MA Dooley 11, Christine Peschken 12, David A Isenberg 13, Anisur Rahman 14, Susan Manzi 15, Soren Jacobsen 16, S Sam Lim 17, Ronald F Van Vollenhoven 18, Ola Nived 19, Diane Kamen 20, Cynthia Aranow 21, Jill Buyon 22, Guillermo Ruiz-Irastorza 23, Ian Bruce 24, Dafna Gladman 25, Paul Fortin 26, Joan T. Merrill 27, Jorge Sanchez-Guerrero 28, Kenneth C Kalunian 29, Kristjan Steinsson 30, Manuel Ramos 31, Asad Zoma 32, Thomas Stoll 33, Munther A Khamashta 34, Murat Inanc 35 and Ann E Clarke 36, 1Research Institute of the McGill University Health Centre, Montreal, QC, Canada, 2Northwestern University, Chicago, IL, 3University Health Network, University of Toronto, Toronto, ON, Canada, 4Queen Elizabeth II Health Science Centre (Nova Scotia Rehab Site), Halifax, NS, Canada, 5University of Birmingham, Birmingham, United Kingdom, 6Johns Hopkins University School of Medicine, Baltimore, MD, 7State University of New York Downstate Medical Center, Brooklyn, NY, 8Cedars-Sinai Medical Centre, Beverly Hills, CA, 9Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea, 10Instituto Nacional de Ciencias Medicas y Nutricion Salvador, Zubiran Vasco de Quiroga, Mexico City, Mexico, 11UnC Kidney Centre, Chapel Hill, NC, 12University of Manitoba, Winnipeg, Canada, 13Centre for Rheumatology, London, United Kingdom, 14University College London, London, United Kingdom, 15Allegheny Health Network, Pittsburg, PA, 16Copenhagen Lupus and Vasculitis Clinic, Copenhagen, Denmark, 17Emory University, Atlanta, GA, 18Amsterdam Rheumatology & Immunology Center, Amsterdam, Netherlands, 19Lund University, Lund, Sweden, 20Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA., Charleston, SC, 21Feinstein Institute for Medical Research, Manhasset, NY, 22NYU School of Medicine, New York, 23Autoimmune Diseases Unit, Hospital Universitario Cruces, Barakaldo, Spain, Barakaldo, Spain, 24University of Manchester, Manchester, United Kingdom, Manchester, England, United Kingdom, 25Toronto Western Hospital, Toronto, Canada, Toronto, ON, Canada, 26Division 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, 27Okalahoma Medical Research Foundation, Oklahoma City, OK, 28Toronto Western Hospital, Toronto, ON, Canada, 29UC San Diego School of Medicine, LaJolla, CA, 30Landspitali, University Hospital, Reykjavik, Iceland, 31Department of Internal Medicine, Hospital Nuestra Señora del Prado, Talavera, Talavera, Spain, Talavera, Spain, 32Lanarkshire Centre for Rheumatology, Hairmyres Hospital, East Kilbride, Scotland, United Kingdom, 33University of Glasgow, Kilbride, Scotland, United Kingdom, 34King's College London School of Medicine, London, United Kingdom, 35Istanbul University, Istanbul Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology, Istanbul, Turkey, 36University of Calgary, Calgary, AB, Canada

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Cancer, Malignancy, medication and risk, Systemic lupus erythematosus (SLE)

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Session Information

Date: Tuesday, November 12, 2019

Session Title: 5T093: SLE – Clinical V: Emerging Knowledge of Current Treatments (2780–2785)

Session Type: ACR Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Many studies of cancer risk in SLE are limited by small sample size or use of administrative data, which rely on billing code diagnoses instead of clinical data. No studies to date focused on incident SLE. We studied cancer risk in the largest-ever cohort of clinically confirmed incident SLE patients.

Methods: Patients meeting ACR criteria for new-onset SLE (within 15 months of diagnosis) were enrolled into the SLICC Inception Cohort, across 32 centres. Patients are followed yearly using a standard protocol, with detailed data collection including SLE Disease Activity Index-2000 (SLEDAI-2K) and damage, and drugs in the past year. New cancer diagnoses are recorded by the examining physician at the annual study visit, and confirmed with chart review including pathology reports.

Multivariate proportional hazard regression was performed, using baseline variables for demographics (age at SLE onset, sex, race/ethnicity), and time-dependent variables for drugs (corticosteroids, anti-malarial drugs, immunosuppressive drugs), smoking, and SLEDAI-2K. As well as cancer over-all, we evaluated risk factors for the most common cancer types.

Results: Of 1848 new-onset SLE patients enrolled between 1999-2011, 1668 had at least one follow-up; these were the sample for the current analysis. End date was the first of death, last visit, or end of study interval for this analysis (Aug. 2015). Baseline demographics are shown in Table 1.

Over 14,215 years (mean 8.5 years) there were 60 cancers (incidence 4. 2 events per 1,000 patient-years). This included 12 breast cancers, 9 non-melanoma skin, 7 lung, 6 hematological, 5 melanoma, 5 prostate, 3 cervical, 3 renal, 2 gastric, 2 head and neck, 2 thyroid, and one each rectal, sarcoma, thymoma, and uterine.   Almost half of the cancer cases (including all of the lung cancers) were associated with baseline  smoking, versus only one-third of those patients who did not develop cancer. Univariate analyses of all cancer types suggested a higher risk of cancer among patients of white race/ethnicity and among those with the highest quartile of disease activity at cohort entry.

However, the multivariate proportional hazard regression indicated that among SLE patients, the over-all cancer risk was related primarily to male sex and older age at SLE diagnosis. In those analyses, the effect of race/ethnicity was not clearly evident, and the point estimate for highest quartile of disease activity actually reversed to suggest a non-significant trend towards lower cancer risk.

In the multivariate analyses specifically for breast cancer, age at SLE diagnoses remained a risk factor, and anti-malarials were associated with a decreased risk. This effect of anti-malarials was not clearly seen for any other cancer type. For non-melanoma skin cancer, both age at SLE diagnosis and cyclophosphamide were strongly linked with risk.

Conclusion: This is the first large, multicentre cohort study to clearly show how different cancer types in SLE are associated with specific risk factors.  Additional follow-up may allow additional determination of the possible effects of disease activity and drugs on cancer subtypes.

Table 1 SLE patients who later developed cancer and those remaining cancer-free

Table 2. Hazard Ratio for cancer in SLE -univariate, full model and partials models-


Disclosure: S. Bernatsky, None; R. Ramsey-Goldman, Exagen, 2; M. Urowitz, Janssen Research & Development, LLC, 2, UCB Pharma, 9; J. Hanly, 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; M. Petri, Eli Lilly and Company, 5, Exagen, 2, 5; E. Ginzler, Ablynx, 5, Aurinia, 2, Genentech, 2, GlaxoSmithKline, 2, Guidepoint Global Gerson Lerman Group, 5, Janssen, 5; D. Wallace, None; S. Bae, None; J. Romero-Diaz, None; M. Dooley, None; C. Peschken, Astra Zeneca, 2, Celgene, 2, Janssen, 2; D. Isenberg, None; A. Rahman, None; S. Manzi, Allegheny Health Network, 3, AstraZeneca, 2, 5; S. Jacobsen, None; S. Lim, 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; O. Nived, None; D. Kamen, None; C. Aranow, EMD Serrono, 2, GlaxoSmithKline, 2, Janssen, 2, Takeda, 2, UCB, Inc, 2, Xencor, 2; J. Buyon, Bristol Myers Squibb, 5, Exagen Diagnostics, 2; G. Ruiz-Irastorza, 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; 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; P. Fortin, None; J. Merrill, Abbvie, 5, Amgen, 5, Astellas, 5, AstraZeneca, 5, BMS, 2, 5, Celgene, 5, EMD Serono, 5, GSK, 2, 5, Idorsia, 5, ILTOO, 5, Immupharma, 5, Incyte, 5, Janssen, 5, Lilly, 5, Remegen, 5, Servier, 5, Xencor, Inc., 2; J. Sanchez-Guerrero, 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; K. Steinsson, None; M. Ramos, None; A. Zoma, None; T. Stoll, None; M. Khamashta, None; M. Inanc, None; A. Clarke, AstraZeneca/MedImmune, 5, Bristol-Myers Squibb, 5, Exagen Diagnostics, 5.

To cite this abstract in AMA style:

Bernatsky S, Ramsey-Goldman R, Urowitz M, Hanly J, Gordon C, Petri M, Ginzler E, Wallace D, Bae S, Romero-Diaz J, Dooley M, Peschken C, Isenberg D, Rahman A, Manzi S, Jacobsen S, Lim S, Van Vollenhoven R, Nived O, Kamen D, Aranow C, Buyon J, Ruiz-Irastorza G, Bruce I, Gladman D, Fortin P, Merrill J, Sanchez-Guerrero J, Kalunian K, Steinsson K, Ramos M, Zoma A, Stoll T, Khamashta M, Inanc M, Clarke A. Cancer Risk in a Large Inception SLE Cohort: Effects of Age, Smoking, and Medications [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/cancer-risk-in-a-large-inception-sle-cohort-effects-of-age-smoking-and-medications/. Accessed March 23, 2023.
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