OP0289 LLDAS (LOW LUPUS DISEASE ACTIVITY STATE), LOW DISEASE ACTIVITY (LDA) AND REMISSION (ON- OR OFF-TREATMENT) PREVENT DAMAGE ACCRUAL IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) PATIENTS IN A MULTINATIONAL MULTICENTER COHORT
Authors: M. F. Ugarte-Gil, J. Hanly, M. B. Urowitz, C. Gordon, S. C. Bae, J. Romero-Diaz, J. Sanchez-Guerrero, S. Bernatsky, A. E. Clarke, D. J. Wallace, D. Isenberg, A. Rahman, J. T. Merrill, P. Fortin, D. D. Gladman, I. N. Bruce, M. A. Petri, E. M. Ginzler, M. A. Dooley, R. Ramsey-Goldman, S. Manzi, A. Jonsen, R. Van Vollenhoven, C. Aranow, M. Mackay, G. Ruiz-Irastorza, S. S. Lim, M. Inanc, K. C. Kalunian, S. Jacobsen, C. Peschken, D. L. Kamen, A. Askanase, B. Pons-Estel, G. S. Alarcon
Journal: Annals of the Rheumatic Diseases (2021)

Background: Remission, LDA and LDAS have been proposed as treatment goals for SLE. However, the independent impact of these states on damage accrual has not been fully evaluated. Objectives: To determine the independent impact of remission (both off &amp; on treatment), LDA, and LLDAS on damage accrual. Methods: We studied a long-term longitudinal multinational SLE cohort, including patients completing at least two annual assessments. Remission off-treatment was defined as a SLEDAI (excluding serology) =0, without prednisone and immunosuppressive (IS) drugs. Remission on-treatment was defined as a SLEDAI (excluding serology) =0, prednisone daily dose&lt;=5 mg/d and maintenance IS drugs. LDA was defined as a SLEDAI (excluding serology) &lt;=2, without prednisone or IS drugs. LLDAS was defined as a SLEDAI &lt;=4 with no activity in major organ systems, with no new features of lupus disease activity compared to the previous assessment, prednisone daily dose&lt;=7.5 mg/d and maintenance IS drugs. Antimalarials were allowed in all groups. Damage accrual was ascertained with the SLICC/ACR damage index (SDI). Univariable and multivariable generalized estimated equation (GEE) negative binomial regression models were used. To create mutually exclusive groups, disease activity was divided into five states: remission off-treatment, remission on-treatment (minus remission off treatment), LDA (minus remission), LLDAS (minus remission and LDA) and not-optimally controlled. The proportion of the time that patients were in the specific state at each visit since cohort entry was determined. Possible effect modifiers and confounders adjusted for included sex, age at diagnosis, race/ethnicity, education, baseline disease duration, follow-up time, the highest-ever glucocorticoid dose prior to cohort entry, antimalarials and SDI. Time-dependent covariates were determined at the same annual visit as disease activity state; the outcome was the increase in the SDI and it was assessed at the subsequent visit. Results: There were 1,652 patients, 1464 (88.6%) were female, mean age at diagnosis was 34.6 (SD 13.4) years and mean baseline disease duration was 5.5 (SD 4.1) months. Patients had a mean follow-up of 6.5 (SD 4.3) years, 11686 visits were included. 763 patients (46.2%) had an increase in SDI score ≥1 during follow-up. 2483 (21.2%) of the visits were classified as remission off-treatment, 2276 (19.5%) as remission on-treatment, 544 (4.7%) as LDA, 657 (5.6%) as LLDAS and 5726 (49.0%) as not-optimally controlled. Being in remission off-treatment, remission on-treatment, LDA and LLDAS were predictive of a lower probability of damage accrual [remission off-treatment IRR=0.403, 95% CI 0.301-0.541); remission on-treatment IRR=0.313 (95% CI 0.218-0.451) LDA: IRR=0.469 (CI 95% CI 0.272-0.809); LLDAS IRR=0.440 (95% CI 0.241-0.803)]. The multivariable model is summarized in Table 1. Table 1. Multivariable GEE model of the impact of disease activity states on damage accrual. Incidence Rate Ratio 95% CI Disease activity state Remission off treatment 0.403 0.301-0.541 Remission on treatment 0.313 0.218-0.451 LDA 0.469 0.272-0.809 LLDAS 0.440 0.241-0.803 Gender, male 1.274 1.086-1.495 Age at diagnosis 1.024 1.020-1.029 Ethnicity Caucasian US Ref. Caucasian other 1.017 0.849-1.217 African 1.467 1.211-1.776 Asian 0.863 0.693-1.075 Hispanic 1.266 1.034-1.550 Other 1.121 0.759-1.656 Educational level, years 0.977 0.957-0.996 Disease duration at baseline 0.960 0.801-1.150 Follow-up time 0.942 0.923-0.960 Antimalarial use 0.786 0.681-0.908 Highest prednisone dose before baseline 1.002 1.001-1.007 SDI before 1.100 1.050-1.1152 LLDAS: Low lupus disease activity state LDA: Low disease activity SDI: SLICC/ACR Damage Index Conclusion: Remission on- and off-treatment, LDA and LLDAS were associated with less damage accrual, even adjusting for possible confounders and effect modifiers. This highlights the importance of treating to target in SLE. Disclosure of Interests: Manuel F. Ugarte-Gil Grant/research support from: Pfizer, Janssen, John Hanly: None declared, Murray B Urowitz: None declared, Caroline Gordon Speakers bureau: UCB, Consultant of: Center for Disease Control, Astra-Zeneca, MFP, Sanofi, UCB, Sang-Cheol Bae: None declared, Juanita Romero-Diaz: None declared, Jorge Sanchez-Guerrero: None declared, Sasha Bernatsky: None declared, Ann E Clarke Consultant of: AstraZeneca, BristolMyersSquibb, GlaxoSmithKline, and Exagen Diagnostics, Daniel J Wallace Grant/research support from: Exagen, David Isenberg: None declared, Anisur Rahman: None declared, Joan T Merrill: None declared, Paul Fortin: None declared, Dafna D Gladman Consultant of: Abbvie, Janssen, Pfizer, Novartis, Amgen, Grant/research support from: Abbvie, Janssen, Pfizer, Novartis, Amgen, Ian N. Bruce: None declared, Michelle A Petri: None declared, Ellen M Ginzler Grant/research support from: Aurinia pharmaceutical, M.A. Dooley: None declared, Rosalind Ramsey-Goldman: None declared, Susan Manzi: None declared, Andreas Jonsen: None declared, Ronald van Vollenhoven Speakers bureau: AbbVie, Galapagos, GSK, Janssen, Pfizer, UCB, Consultant of: Abbvie, AstraZeneca, Biogen, Biotest, Celgen, Galapagos, Gilead, Janssen, Pfizer, Sanofie, Servier, UCB, Vielabo, Grant/research support from: BMS, GSK, Lilly, UCB, Cynthia Aranow: None declared, Meggan Mackay: None declared, Guillermo Ruiz-Irastorza: None declared, S. Sam Lim: None declared, Murat Inanc: None declared, Kenneth C Kalunian Consultant of: Roche, Biogen, Janssen, AstraZeneca, Eli Lilly, Genetech, Gilead, ILTOO, Nektar, Viela, Equillium, Bristol-Meyers Squibb, Soren Jacobsen Grant/research support from: BMS, Christine Peschken: None declared, Diane L Kamen: None declared, Anca Askanase Consultant of: Abbvie, Grant/research support from: Glaxo Smith Kline, Astra Zeneca, Janssen, Eli Lilly and Company, Mallinckrodt, Pfizer, Bernardo Pons-Estel Consultant of: GSK, Janssen, Graciela S Alarcon: None declared.