Predictors of Remission (on and off Treatment) and Lupus Low Disease Activity State (LLDAS) in Systemic Lupus Erythematosus (SLE): Data from a Multinational, Multicenter SLICC (Systemic Lupus International Collaborating Clinics) Cohort

Manuel Ugarte-Gil¹, Guillermo Ruiz-Irastorza², Dafna Gladman³, Murray Urowitz⁴, Ann Clarke⁵, John Hanly⁶, Caroline Gordon⁷, Sang-Cheol Bae⁸, Juanita Romero-Diaz⁹, Jorge Sanchez-Guerrero¹⁰, Sasha Bernatsky¹¹, Daniel Wallace¹², David Isenberg¹³, Anisur Rahman¹⁴, Joan Merrill¹⁵, Paul R Fortin¹⁶, Ian N. Bruce¹⁷, Michelle Petri¹⁸, Ellen Ginzler¹⁹, Mary Anne Dooley²⁰, Rosalind Ramsey-Goldman²¹, Susan Manzi²², Andreas Jnsen²³, Ronald F van Vollenhoven²⁴, Cynthia Aranow²⁵, Meggan Mackay²⁵, S Sam Lim²⁶, Murat Inanc²⁷, Kenneth Kalunian²⁸, Soren Jacobsen²⁹, Christine Peschken³⁰, Diane Kamen³¹, Anca Askanase³², Bernardo A. Pons-Estel³³ and Graciela Alarcn³⁴, ¹Hospital Guillermo Almenara Irigoyen, Essalud/Universidad Científica del Sur, Lima, Peru, ²Hospital Universitario Cruces, University of the Basque Country, Bizkaia, Spain, ³Schroeder Arthritis Institute, Krembil Research Institute, Toronto Western Hospital, Toronto, ON, Canada, ⁴Center for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University of Toronto, Lupus Clinic, Toronto, ON, Canada, ⁵University of Calgary, Calgary, AB, Canada, ⁶Dalhousie University, Halifax, NS, Canada, ⁷Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom, ⁸Hanyang University Medical Center, Seoul, Republic of Korea, ⁹Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Ciudad de México, Federal District, Mexico, ¹⁰Instituto Nacional de Ciencias Médicas y Nutrición, Inmunología y Reumatología, Mexico City, Mexico, ¹¹McGill University, Montréal, QC, Canada, ¹²Cedars-Sinai, Los Angeles, CA, ¹³Centre for Rheumatology, University College London, London, United Kingdom, ¹⁴University College London, London, United Kingdom, ¹⁵Oklahoma Medical Research Foundation, Oklahoma City, OK, ¹⁶CHU de Quebec - Universite Laval, Québec City, QC, Canada, ¹⁷University of Manchester, Manchester, United Kingdom, ¹⁸Johns Hopkins University School of Medicine, Baltimore, MD, ¹⁹SUNY Downstate Health Sciences University, Brooklyn, NY, ²⁰Raleigh Neurology Associates, Chapel Hill, NC, ²¹Northwestern University, Chicago, IL, ²²Allegheny Health Network, Wexford, PA, ²³Lund University, Lund, Sweden, ²⁴Amsterdam University Medical Centers, Department of Rheumatology and Clinical Immunology, Rheumatology and Immunology Center ARC, Amsterdam, Netherlands, ²⁵Feinstein Institutes for Medical Research, Manhasset, NY, ²⁶Department of Medicine, Division of Rheumatology, Emory University School of Medicine, Atlanta, GA, ²⁷Istanbul University Faculty of Medicine, Istanbul, Turkey, ²⁸UC San Diego, La Jolla, CA, ²⁹Rigshospitalet, Copenhagen, Denmark, ³⁰University of Manitoba, Winnipeg, MB, Canada, ³¹Medical University of South Carolina, Charleston, SC, ³²Columbia University Medical Center, New York, NY, ³³Grupo Oroo - Centro Regional de Enfermedades Autoinmunes y Reumticas (GO-CREAR), Rosario, Argentina, ³⁴University of Alabama at Birmingham, Birmingham, AL

Meeting: ACR Convergence 2021

Keywords: Disease Activity, Outcome measures, risk factors, Systemic lupus erythematosus (SLE)

Session Information

Date: Monday, November 8, 2021

Title: SLE – Diagnosis, Manifestations, & Outcomes Poster III: Outcomes (1257–1303)

Session Type: Poster Session C

Session Time: 8:30AM-10:30AM

Background/Purpose: Remission and LLDAS have been proposed as the goals for the treatment of SLE patients. However, the predictors of each state remain unknown. The aim of this study was to determine predictors of remission and LLDAS.

Methods: We studied patients from a long-term longitudinal multinational, multiethnic SLE inception cohort followed for a mean of 6.5 years; eligible patients were those completing at least two annual visits. Three outcomes were established: 1. Remission off treatment, defined as a SLEDAI-2K (excluding serology) =0, without prednisone (PDN) and immunosuppressive drugs (IS). 2. Remission on treatment, defined as a SLEDAI-2K (excluding serology) =0, PDN≤5 mg/d and maintenance IS drugs (based on the 2017 DORIS definition). 3. LLDAS, defined as a SLEDAI-2K≤4 with no activity in major organ systems, with no new features of lupus disease activity compared to the previous assessment, PDN≤7.5 mg/d and maintenance IS drugs (based on the Asia Pacific Lupus Consortium definition). Antimalarials were allowed in all groups. Possible predictors included were sex, age at diagnosis, ethnicity, educational level, SLEDAI-2K at cohort entry, disease duration at baseline, highest PDN dose before baseline, number of methylprednisolone (MP) IV pulses as well as mean dose per pulse before baseline. Antimalarial use and the SLICC/ACR damage index (SDI) were time-dependent covariates. Three outcome groups were defined after exclusion of patients who had already achieved the outcome at baseline. Univariable and multivariable interval-censored survival regression models for each outcome (stepwise selection procedure, including age at diagnosis and sex in all models) were used. Alternative models including SLEDAI-2K’s domains instead of the global score were performed.

Results: Remission off treatment was achieved in 367 of 1243 patients (29.5%), remission on treatment in 749 of 1185 patients (63.2%), and LLDAS in 833 of 1151 patients (72.4%). Non-Caucasian ethnicity (in particular African) as well as a higher SLEDAI-2K scores and glucocorticoid (GC) dose (oral PDN as well as MP pulses) were associated with a lower probability of achieving these states. Older age at diagnosis and antimalarial use during the follow-up period were associated with a higher probability of remission on treatment and LLDAS. Disease duration at baseline was associated with a lower probability of remission off treatment. Sex, educational level, and the SDI were not associated with any of these states. These data are summarized in Table 1. In the alternative models, the SLEDAI-2K domains associated with a lower probability of achieving at least one of the outcomes were mucocutaneous (all outcomes), renal (remission off treatment and LLDAS), fever (remission off treatment) and musculoskeletal and neurological (LLDAS).

Conclusion: Older age at diagnosis and antimalarial use during follow-up were associated with a higher probability of achieving these treatment goals; on the other hand, non-Caucasian ethnicity (in particular African), a higher SLEDAI-2K, a longer disease duration at baseline and a higher dose of GC (PDN or MP pulses) early in the course of the disease were associated with a lower probability of achieving these treatment goals.

Disclosures: M. Ugarte-Gil, Pfizer, 5, Janssen, 5; G. Ruiz-Irastorza, None; D. Gladman, AbbVie, 2, 5, Amgen, 2, 5, Eli Lilly, 2, 5, Galapagos, 2, 5, Gilead, 2, 5, Janssen, 2, 5, Novartis, 2, 5, Pfizer, 2, 5, UCB, 2, 5, Celgene, 2, 5, Bristol Myers Squibb, 2, 5; M. Urowitz, GlaxoSmithKline, 2, 5, 6, UCB, 2, Lilly, 6, AstraZeneca, 2; A. Clarke, AstraZeneca, 2, GSK, 6, BMS, 2, Exagen Diagnostics, 2; J. Hanly, None; C. Gordon, Centre for Disease Control, 2, 6, Astra-Zeneca, 2, 6, MGP, 2, 6, Sanofi, 2, 6, UCB, 2, UCB, 5, 6; S. Bae, None; J. Romero-Diaz, None; J. Sanchez-Guerrero, None; S. Bernatsky, None; D. Wallace, GlaxoSmithKline, 2, 6, Eli Lilly and Company, 2, 6, AstraZeneca, 2, 6, Aurunia, 2, 6, EMD Serono, 2; D. Isenberg, None; A. Rahman, Lilly, 6; J. Merrill, GlaxoSmithKline, 2, 5, UCB, 2, AbbVie, 2, EMD Serono, 2, Remegen, 2, Celgene/Bristol Myers Squibb, 2, AstraZeneca, 2, 5, Daiichi Sankyo, 2, Servier, 2, Immupharma, 2, Amgen, 2, Janssen, 2, Lilly, 2, Genentech, 2, Resolve, 2, Alpine, 2, Aurinia, 2, Astellas, 2, Alexion, 2, Provention, 2; P. Fortin, Lilly, 1, AbbVie, 1, AstraZeneca, 1; I. Bruce, None; M. Petri, Alexion, 1, Amgen, 1, Astrazeneca, 1, 5, Aurinia, 5, 6, Eli Lilly, 5, Emergent Biosolutions, 1, Exagen, 5, Gilead Biosciences, 2, GSK, 1, 5, IQVIA, 1, Idorsia Pharmaceuticals, 2, Janssen, 1, 5, Merck EMD Serono, 1, Momenta Pharmaceuticals, 2, PPD Development, 1, Sanofi, 2, Thermofisher, 5, UCB Pharmaceuticals, 2; E. Ginzler, None; M. Dooley, None; R. Ramsey-Goldman, None; S. Manzi, Astra Zenecs, 2, 5, Cugene, 2, Eli Lilly, 2, Exagen, 2, 5, 10, UCB, 2, GSK, 2; A. Jnsen, None; R. van Vollenhoven, Bristol-Myers Squibb, 2, 5, 6, GlaxoSmithKline, 2, 5, 6, Eli Lilly, 5, Pfizer, 2, 5, 6, Roche, 5, UCB, 2, 5, 6, AbbVie, 2, 6, AstraZeneca, 2, 6, Biogen, 2, 6, Biotest,, 2, 6, Galapagos, 2, 6, Gilead, 2, 6, Janssen, 2, 6, Sanofi, 2, 6, Servier, 2, 6, Velabio, 2, 6, BMS, 5, GSK, 5, Celgene, 2, 6; C. Aranow, GlaxoSmithKline, 2, 5; M. Mackay, None; S. Lim, Bristol Myers Squibb, 5, GlaxoSmithKline, 2, ACR, 4, AstraZeneca, 5, Pfizer, 2, UCB, 2; M. Inanc, None; K. Kalunian, Amgen, 2, AbbVie, 2, AstraZeneca, 2, Biogen, 2, Bristol Myers Squibb, 2, Eli Lilly, 2, Equillium, 2, Genentech/Roche, 2, Gilead, 2, Janssen, 2, Lupus Research, 5, Pfizer, 5, Sanford Consortium, 5, Vielabio, 2, Aurinia, 2, Alliance, 2, Nektar, 2; S. Jacobsen, None; C. Peschken, AstraZeneca, 2, GlaxoSmithKline, 2, Eli Lilly, 2; D. Kamen, None; A. Askanase, GSK, 2, 5, AstraZeneca, 1, 5, Amgen, 1, Aurinia, 2, Abbvie, 1, Pfizer, 5, Eli Lilly, 5, Idorsia, 5; B. Pons-Estel, Janssen, 5, Glaxo Smith Kline, 6; G. Alarcn, None.

To cite this abstract in AMA style:

Ugarte-Gil M, Ruiz-Irastorza G, Gladman D, Urowitz M, Clarke A, Hanly J, Gordon C, Bae S, Romero-Diaz J, Sanchez-Guerrero J, Bernatsky S, Wallace D, Isenberg D, Rahman A, Merrill J, Fortin P, Bruce I, Petri M, Ginzler E, Dooley M, Ramsey-Goldman R, Manzi S, Jnsen A, van Vollenhoven R, Aranow C, Mackay M, Lim S, Inanc M, Kalunian K, Jacobsen S, Peschken C, Kamen D, Askanase A, Pons-Estel B, Alarcn G. Predictors of Remission (on and off Treatment) and Lupus Low Disease Activity State (LLDAS) in Systemic Lupus Erythematosus (SLE): Data from a Multinational, Multicenter SLICC (Systemic Lupus International Collaborating Clinics) Cohort [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/predictors-of-remission-on-and-off-treatment-and-lupus-low-disease-activity-state-lldas-in-systemic-lupus-erythematosus-sle-data-from-a-multinational-multicenter-slicc-systemic-lupus-internat/. Accessed .

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