Outcomes After Hydroxychloroquine Reduction or Discontinuation in a Multinational Inception Cohort of Systemic Lupus

Celline Almeida-Brasil¹, John Hanly², Murray Urowitz³, Ann Clarke⁴, Rosalind Ramsey-Goldman⁵, Caroline Gordon⁶, Michelle Petri⁷, Ellen M Ginzler⁸, Daniel J Wallace⁹, Sang-Cheol Bae¹⁰, Juanita Romero-Diaz¹¹, Mary Ann Dooley¹², Christine A. Peschken¹³, David Isenberg¹⁴, Anisur Rahman¹⁴, Susan Manzi¹⁵, Søren Jacobsen¹⁶, S. Sam Lim¹⁷, Ronald Van Vollenhoven¹⁸, Ola Nived¹⁹, Andreas Jönsen¹⁹, Diane Kamen²⁰, Cynthia Aranow²¹, Guillermo Ruiz-Irastorza²², Jorge Sanchez-Guerrero²³, Dafna Gladman²⁴, Paul Fortin²⁵, Graciela Alarcón²⁶, Joan Merrill²⁷, Kenneth Kalunian²⁸, Manuel Ramos-Casals²⁹, Kristjan Steinsson³⁰, Asad Zoma³¹, Anca Askanase³², Munther Khamashta³³, Ian Bruce³⁴, Murat Inanc³⁵ and Sasha Bernatsky³⁶, ¹McGill University, Montreal, Canada, ²QEII Health Sciences Centre, Halifax, Canada, ³University Health Network, University of Toronto, Toronto, ON, Canada, ⁴University of Calgary, Calgary, Canada, ⁵Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, ⁶University of Birmingham, Birmingham, England, United Kingdom, ⁷Johns Hopkins University School of Medicine, Baltimore, ⁸SUNY Downstate Health Sciences University, Brooklyn, ⁹Cedars-Sinai Medical Center, Beverly Hills, CA, ¹⁰Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea, ¹¹Salvador Zubirán National Institute of Health Sciences and Nutrition, Mexico City, Mexico, ¹²UNC Health, Chapel Hil, ¹³University of Manitoba, Winnipeg, Canada, ¹⁴University College London, London, United Kingdom, ¹⁵Temple University, Philadelphia, ¹⁶University of Copenhagen, Copenhagen, Denmark, ¹⁷Emory University, Atlanta, GA, ¹⁸University of Amsterdam, Amsterdam, Netherlands, ¹⁹Lund University, Lund, Sweden, ²⁰Medical University of South Carolina, Charleston, SC, ²¹Feinstein Institutes for Medical Research, Manhasset, NY, ²²Hospital Universitario Cruces, Bizkaia, Spain, ²³University of Toronto, Toronto, Canada, ²⁴Krembil Research Institute, Toronto Western Hospital, Toronto, ON, Canada, ²⁵CHU de Quebec - Universite Laval, Quebec, Canada, ²⁶Division of Clinical Immunology and Rheumatology, Department of Medicine, School of Medicine, The University of Alabama at Birmingham; Department of Medicine, School of Medicine; Universidad Peruana Cayetano, Heredia, Alabama, ²⁷New York University, New York, ²⁸University of California San Diego, La Jolla, CA, ²⁹University of Barcelona, Barcelona, Spain, ³⁰Reykjavik University, Reykjavik, Iceland, ³¹University of Glasgow, Glasgow, United Kingdom, ³²Columbia University College of Physicians & Surgeons, New York, NY, ³³King's College London, London, United Kingdom, ³⁴The University of Manchester, Manchester, United Kingdom, ³⁵Department of Rheumatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey, ³⁶The Research Institute of the McGill University Health Centre, Montreal, ON, Canada

Meeting: ACR Convergence 2020

Keywords: Cohort Study, Disease-Modifying Antirheumatic Drugs (Dmards), Epidemiology, risk factors, Systemic lupus erythematosus (SLE)

Session Information

Date: Monday, November 9, 2020

Title: SLE – Treatment Poster II

Session Type: Poster Session D

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

Background/Purpose: Hydroxychloroquine (HCQ) is a cornerstone treatment for several autoimmune diseases including Systemic Lupus Erythematosus (SLE). Recently, concerns arose regarding HCQ shortages for SLE patients, due to its use as a potential COVID-19 treatment. Although some patients may remain well after reducing or stopping therapy, others will have potentially life-threatening complications related to SLE flares. We evaluated if HCQ reduction or discontinuation is associated with increased risk of poor outcomes.

Methods: We analyzed prospective data from the Systemic Lupus International Collaborating Clinics (SLICC) cohort, which includes SLE patients from 33 sites in Europe, Asia, and North America, enrolled within 15 months of diagnosis and followed annually, from 1999 to 2019. In patients receiving HCQ, we identified two sub-cohorts, one who reduced HCQ and one who stopped HCQ. We did not require patients to be in disease remission at the time of HCQ reduction/discontinuation for these analyses. Time zero for these sub-cohorts was the date of the first HCQ reduction/discontinuation. For comparison, we identified a third group of patients remaining on HCQ. A poor outcome was defined as either subsequent need for SLE therapy augmentation (steroids or other immunosuppressives), increase of ≥4 points in the SLE Disease Activity Index-2000 (SLEDAI-2K) or hospitalization for SLE. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for poor outcomes among the three HCQ exposure groups. Models were adjusted for demographics and baseline clinical characteristics.

Results: A total of 1460 patients were included (89% female, 52% Caucasian). Patients in the HCQ reduction group contributed 1087 person-years, those discontinuing HCQ contributed 677 person-years, and those maintaining HCQ contributed 1649 person-years. HCQ dose reduction or discontinuation occurred in many patients (40%) with a SLEDAI-2K >4. The crude poor outcome rate was significantly lower in the HCQ maintenance group (31.6 events per 100 person-years, 95% CI 29.0, 34.5) than in the reduction (43.0, 95% CI 39.3, 47.1) and in the discontinuation (43.0, 95% CI 38.3, 48.2) groups. Patients reducing or discontinuing HCQ had higher adjusted HRs for poor outcomes versus those maintaining HCQ (Table 1). Other factors independently associated with poor outcomes included active SLE and use of prednisone or immunosuppressive drugs, all measured at time zero.

Conclusion: Patients reducing or discontinuing HCQ are at greater risk of having a poor outcome versus those maintaining the drug. These analyses do not account for reasons HCQ was reduced/discontinued. Regardless, baseline disease activity, prednisone and immunosuppressive drugs were associated with the risk of poor outcomes in SLE patients reducing, discontinuing, or maintain HCQ.

Hazard ratios (HRs), and 95% confidence intervals (CIs) for poor outcomes in HCQ-exposed SLE patients

Disclosure: C. Almeida-Brasil, None; J. Hanly, None; M. Urowitz, None; A. Clarke, AstraZenca, 5, Exagen Diagnostics, 5; R. Ramsey-Goldman, None; C. Gordon, UCB, 1, 2, 3, 4, CDC, 1, MGP, 1; M. Petri, AbbVie, 5, Amgen, 5, AstraZeneca, 2, 5, BMS, 5, Decision Resources, 5, GSK, 2, 5, INOVA, 5, IQVIA, 5, Janssen, 5, Eli Lilly, 2, 5, Merck EMD Serono, 5, Sanofi Japan, 5, Thermofisher, 5, UCB, 5, Exagen, 2; E. Ginzler, Aurinia Pharmaceuticals, Inc., 2; D. Wallace, Exagen, 1, 2, Exagen, 1, 2; S. Bae, None; J. Romero-Diaz, None; M. Dooley, None; C. A. Peschken, None; D. Isenberg, None; A. Rahman, None; S. Manzi, None; S. Jacobsen, BMS, 2; S. Lim, None; R. Van Vollenhoven, None; O. Nived, None; A. Jönsen, None; D. Kamen, None; C. Aranow, None; G. Ruiz-Irastorza, None; J. Sanchez-Guerrero, None; D. Gladman, AbbVie, 2, 5, Amgen, 2, 5, Janssen, 2, 5, Novartis, 2, 5, Pfizer, 2, 5, UCB, 2, 5, Bristol-Myers Squibb, 5, Gilead, 5, Galapagos, 5, Celgene, 2, 5, Eli Lilly, 2, 5; P. Fortin, None; G. Alarcón, None; J. Merrill, None; K. Kalunian, Roche, 5, Biogen, 5, Janssen, 5, AstraZeneca, 5, Lupus Research Alliance, 2, Pfizer, 2, Sanford Consortium, 2, Eli Lilly, 5, Genetech, 5, Gilead, 5, ILTOO, 5, Nektar, 5, Viela, 5, Equillium, 5, Bristol-Meyers Squibb, 5; M. Ramos-Casals, None; K. Steinsson, None; A. Zoma, None; A. Askanase, Glaxo Smith Kline, 2, Astra Zeneca, 2, Janssen, 2, Eli Lilly and Company, 2, Abbvie, 5, Mallinckrodt, 2, Regeneron, 9, Pfizer, 2, Bristol Myers Squibb, 9; M. Khamashta, None; I. Bruce, None; M. Inanc, None; S. Bernatsky, None.

To cite this abstract in AMA style:

Almeida-Brasil C, Hanly J, Urowitz M, Clarke A, Ramsey-Goldman R, Gordon C, Petri M, Ginzler E, Wallace D, Bae S, Romero-Diaz J, Dooley M, A. Peschken C, Isenberg D, Rahman A, Manzi S, Jacobsen S, Lim S, Van Vollenhoven R, Nived O, Jönsen A, Kamen D, Aranow C, Ruiz-Irastorza G, Sanchez-Guerrero J, Gladman D, Fortin P, Alarcón G, Merrill J, Kalunian K, Ramos-Casals M, Steinsson K, Zoma A, Askanase A, Khamashta M, Bruce I, Inanc M, Bernatsky S. Outcomes After Hydroxychloroquine Reduction or Discontinuation in a Multinational Inception Cohort of Systemic Lupus [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/outcomes-after-hydroxychloroquine-reduction-or-discontinuation-in-a-multinational-inception-cohort-of-systemic-lupus/. Accessed .

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