Document resource
Low disease activity and remission are recognized as important goals in the treatment of patients with lupus and as valuable outcomes in epidemiological research and in clinical trials. The former is most often defined using the lupus low disease activity state (LLDAS) 1, while the latter was defined in 2021 by the Definition Of Remission In Systemic Lupus Erythematosus (DORIS) group and has been studied and used widely since then.2 It has become clear that DORIS remission can be attained in practice and that it corresponds to a range of better outcomes for the patient3. However, DORIS remission is based on clinical parameters and does not reflect the underlying processes and unsurprisingly, patients who achieve DORIS remission may yet experience flares of the disease.Recent observations on small numbers of patients who were treated with chimeric antigen-receptor-T cells (CAR-T cells) have yielded an encouraging new perspective: along with the complete depletion of B cells, autoantibody titers decreased and rapid and complete clinical responses were seen in many patients;4 and even more importantly, while B-cell reconstitution took place as expected and vaccine responses were restored, autoantibodies did not re-emerge and clinical relapses did not occur in the lupus patients reported to date; in some patients a treatment-free remission for more than two years has now been documented. These observations therefore provide the perspective that, at least for some patients, a more complete remission can be attained that is characterized by:DORIS clinical remissionImmunological resetNo need for further therapyLonger durationThe DORIS group has now embarked on the process of defining ‘DORIS-PLUS’, a suitable definition incorporating some or all the elements above, for use alongside the DORIS definition.In parallel, the Systemic Lupus Collaborating Clinics (SLICC) group has initiated the LOREL study, which aims to determine how often such a profound state of remission is seen in large observational cohorts of patients, and whether predictors for this state can be identified.Taken together, these developments suggest future therapeutic targets for lupus may evolve to prioritize LLDAS for most patients, DORIS for many, and increasingly, DORIS+ for a smaller but growing number.Learning Objectives At the end of this presentation participants will be able to:Discuss the published and reported experiences with the definition of remission in SLE (DORIS)Explain the basic ideas of having low disease activity and remission as targets in clinical care and as outcomes in epidemiological research and clinical trialsDescribe the recent developments in therapeutics that may allow more ambitious therapeutic targets in the futureDiscuss the current work by the DORIS group towards defining ‘DORIS-PLUS’References Franklyn K, Lau CS, Navarra SV, et al. Asia-pacific lupus collaboration. definition and initial validation of a lupus low disease activity state (LLDAS). Ann Rheum Dis. 2016 Sep;75(9):1615–21. doi: 10.1136/annrheumdis-2015-207726. Epub 2015 Oct 12.van Vollenhoven RF, Bertsias G, Doria A, et al. 2021 doris definition of remission in SLE: Final recommendations from an international task force. Lupus Sci Med. 2021;8(1) doi: 10.1136/lupus-2021-000538Parodis I, Lindblom J, Levy RA, et al. Attainment of remission and low disease activity after treatment with belimumab in patients with systemic lupus erythematosus: a post-hoc analysis of pooled data from five randomised clinical trials. Lancet Rheumatol. 2024 Nov;6(11):e751-e761. doi: 10.1016/S2665-9913(24)00162-0. Epub 2024 Aug 26.Muller F, Taubmann J, Bucci L, et al. CD19 CAR T-cell therapy in autoimmune disease - A case series with follow-up. N Engl J Med. 2024;390(8):687–700. doi: 10.1056/NEJMoa2308917