www.thelancet.com/rheumatology Vol 1 October 2019 e103 Articles Lancet Rheumatol 2019; 1: e103–10 See Comment page e77 *Contributed equally School of Clinical Sciences, Monash University, Melbourne, VIC, Australia (V Golder MBBS, R Kandane-Rathnayake PhD, A Hoi MBBS, Prof E F Morand MBBS); Department of Rheumatology, The University of Melbourne, Melbourne, VIC, Australia (M Huq MSc, M Nikpour MBBS); Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand (Prof W Louthrenoo MD); Department of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Guishan Township, Taiwan (Prof S F Luo MD, Y-J J Wu MD); Rheumatology Division, National University Hospital, Singapore (A Lateef MBBS); Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia (S Sockalingam MD); Joint and Bone Center, University of Santo Tomas Hospital, Manila, Philippines (Prof S V Navarra MD, L Zamora MD); Department of Internal Medicine, University of Padjadjaran, Bandung, Indonesia (L Hamijoyo MD); Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan (Y Katsumata MD, Prof M Harigai MD); Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore (M Chan MD); South Western Sydney Clinical School, University of New South Wales, Sydney, NSW, Australia (S O’Neill BMed); Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia (S O’Neill); Department of Rheumatology, Royal Adelaide Hospital, Evaluation of remission definitions for systemic lupus erythematosus: a prospective cohort study Vera Golder, Rangi Kandane-Rathnayake, Molla Huq, Worawit Louthrenoo, Shue Fen Luo, Yeong-Jian Jan Wu, Aisha Lateef, Sargunan Sockalingam, Sandra V Navarra, Leonid Zamora, Laniyati Hamijoyo, Yasuhiro Katsumata, Masayoshi Harigai, Madelynn Chan, Sean O’Neill, Fiona Goldblatt, Chak Sing Lau, Zhan Guo Li, Alberta Hoi, Mandana Nikpour*, Eric F Morand*, for the Asia Pacific Lupus Collaboration Summary Background Validated outcome measures are needed from which to derive treatment strategies for systemic lupus erythematosus (SLE). However, no defnition of remission for SLE has been widely adopted. The Defnitions of Remission in Systemic Lupus Erythematosus (DORIS) group has proposed a framework with multiple potential defnitions of remission. In this study, we aimed to assess the attainability and efect on disease outcomes of the DORIS defnitions of remission, compared with the lupus low disease activity state (LLDAS), in patients with SLE. Methods In this prospective cohort study, we enrolled patients with SLE from 13 international centres that are part of the Asia Pacifc Lupus Collaboration. Eligible patients were older than 18 years and fulflled one of two classifcation criteria for SLE (1997 American College of Rheumatology criteria or the 2012 Systemic Lupus International Collaborating Clinics criteria). Visits were according to clinical need, with a minimum frequency of one visit per 6 months. We assessed attainment of remission on the basis of the eight DORIS defnitions of remission, which varied in terms of serological activity, glucocorticoid use, and use of immunosuppresive agents; attainment of LLDAS; and disease fares at each visit. Irreversible organ damage accrual was recorded annually. Our primary aim was to assess exposure of patients to each of the remission defnitions or LLDAS, and the respective association of these states with accrual of irreversible organ damage as the primary outcome measure. Occurrence of disease fares was the key secondary outcome. We used time-dependent Cox proportional hazards models and generalised linear models to assess DORIS defnitions of remission and LLDAS in terms of their association with damage accrual and disease fares. Findings Between May 1, 2013, and Dec 31, 2016, 1707 patients with SLE were recruited and followed for a mean of 2·2 years (SD 0·9), totalling 12 689 visits. Remission, depending on DORIS defnition, was achieved in 581 (4·6%) to 4546 (35·8%) of 12 689 visits. Spending 50% or more of observed time in any remission state was associated with a signifcant reduction in damage accrual, except for the two most stringent remission defnitions, for which the frequency of attainment was lowest. Remission defnitions disallowing serological activity were associated with the greatest reductions in disease fares. LLDAS was more attainable than any remission defnition and was associated with a similar magnitude of protection from damage accrual and disease fares. Sustained remission and LLDAS were associated with a wider spread of efect sizes for reduction in risk of damage. By analysing patients who met the defnition for LLDAS but not remission, we found that LLDAS was signifcantly associated with reduction in damage accrual, independent of all defnitions of remission, except the least stringent. Interpretation Attainment of remission was associated with signifcant reductions in damage accrual and disease fares. LLDAS was more achievable than remission based on the DORIS criteria, but was similarly protective. Remission defnitions with less stringency might be insufciently distinct from LLDAS to substantially afect outcome measures, and further studies are needed to distinguish the protective efects of the various remission defnitions. Funding UCB, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca. Copyright © 2019 Elsevier Ltd. All rights reserved. Introduction The use of treat-to-target approaches based on validated outcome measures has transformed clinical trials and practice for chronic diseases such as diabetes and hyper- tension. 1 Treat-to-target became the standard of care in rheumatoid arthritis after it was shown that achievement of the treatment targets of remission or low disease activity was associated with signifcant reduction in structural joint damage. 2 In 2014, an international working group highlighted as an urgent priority the need for valid- ated outcome measures from which to derive treatment strategies for systemic lupus erythematosus (SLE). 3 Mort- ality in patients with SLE is strongly associated with damage accrual, with causative factors including poorly controlled disease activity, glucocorticoid use, and com- plications of long-term immunosuppression. 4,5 Therefore,