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Review
. 2023 Dec;10(6):1459-1477.
doi: 10.1007/s40744-023-00601-w. Epub 2023 Oct 5.

Targeting DORIS Remission and LLDAS in SLE: A Review

Agner R Parra Sánchez  1 , Ronald F van Vollenhoven  2 , Eric F Morand  3 , Ian N Bruce  4   5 , Rangi Kandane-Rathnayake  3 , Gudrun Weiss  6 , Raj Tummala  7 , Hussein Al-Mossawi  8 , Alessandro Sorrentino  6
Affiliations
Review

Targeting DORIS Remission and LLDAS in SLE: A Review

Agner R Parra Sánchez et al. Rheumatol Ther. 2023 Dec.

Erratum in

  • Correction: Targeting DORIS Remission and LLDAS in SLE: A Review.
    Parra Sánchez AR, van Vollenhoven RF, Morand EF, Bruce IN, Kandane-Rathnayake R, Weiss G, Tummala R, Al-Mossawi H, Sorrentino A. Parra Sánchez AR, et al. Rheumatol Ther. 2024 Aug;11(4):1059-1061. doi: 10.1007/s40744-024-00679-w. Rheumatol Ther. 2024. PMID: 38847996 Free PMC article. No abstract available.

Abstract

Remission is the established therapeutic goal for patients with systemic lupus erythematosus (SLE) and is currently defined by the widely adopted Definition Of Remission In SLE (DORIS) criteria. Attainment of remission is rare in the clinical setting, thus an alternative, pragmatic treatment target of low disease activity, as defined by the Lupus Low Disease Activity State (LLDAS), provides a less stringent and more attainable treatment goal for a wider proportion of patients compared with DORIS remission. Randomized controlled trials and real-world analyses have confirmed the positive clinical benefits of achieving either DORIS remission or LLDAS. The treat-to-target (T2T) approach utilizes practical clinical targets to proactively tailor individual treatment regimens. Studies in other chronic inflammatory diseases using the T2T approach demonstrated significantly improved clinical outcomes and quality-of-life measures compared with established standard of care. However, such trials have not yet been performed in patients with SLE. Here we review the evolution of DORIS remission and LLDAS definitions and the evidence supporting the positive clinical outcomes following DORIS remission or LLDAS attainment, before discussing considerations for implementation of these outcome measures as potential T2T objectives. Adoption of DORIS remission and LLDAS treatment goals may result in favorable patient outcomes compared with established standard of care for patients with SLE.

Keywords: DORIS remission; LLDAS; Low disease activity; Remission; Systemic lupus erythematosus; Treat-to-target approach.

Plain language summary

Systemic lupus erythematosus (SLE) is a complex disease that can affect many organs. It can lead to life-threatening complications and poor quality of life. As SLE is very different in each person, it can be challenging to measure disease activity. Doctors are encouraged to set clinical targets to tailor treatment for each patient. Clinical targets include scoring systems that measure disease improvement. Remission is an established clinical target. When a patient is in remission, disease activity is controlled, and the patient does not experience any symptoms. As remission is difficult to achieve, experts developed a more realistic yet still favorable state. This is the lupus low disease activity state, when lupus symptoms are minimal on stable therapy. Doctors use remission and low disease activity in clinical trials to compare existing SLE drugs with new treatments, including biologic drugs. Biologics target key parts of the immune system to help suppress SLE. In this review, we looked at recent clinical trials and found that biologic drugs can help patients achieve remission or low disease activity. Patients who achieved these clinical targets had slower disease progression and improved quality of life. Clinical trials in SLE should continue to use remission and low disease activity targets to help compare treatments. Doctors are encouraged to use them in their routine clinics as treatment targets to measure SLE disease control. Low disease activity state may be particularly helpful as an initial target for patients who are not yet in remission.

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Conflict of interest statement

Agner R. Parra Sánchez has received grant/research support (institutional grants) from AstraZeneca; received support for attending meetings and/or travel from Amsterdam UMC. The work of ARPS is supported by the European Union’s Horizon 2020 research and innovation program (“ARCAID”; www.arcaid-h2020.eu; grant agreement nr. 847551). Ronald F. van Vollenhoven has received grant/research support from Bristol Myers Squibb (BMS) and UCB; received support for educational programs from AstraZeneca, Galapagos, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB; received consulting fees from AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Pfizer, and UCB; and received speaking fees and/or honoraria from AbbVie, AstraZeneca, BMS, Galapagos, GlaxoSmithKline (GSK), Janssen, Pfizer, and UCB. Eric F. Morand has received grant support from AbbVie, Amgen, AstraZeneca, Biogen, BMS, Eli Lilly and Company, EMD Serono, Genentech, GSK, Janssen, and UCB Pharma; received consulting fees from AbbVie, Amgen, AstraZeneca, Biogen, BMS, Eli Lilly and Company, EMD Serono, Genentech, GSK, Janssen, Novartis, Servier, Wolf, and Zenas; received speaking fees and/or honoraria from AstraZeneca, Biogen, BMS, EMD Serono, and Gilead; received support for attending meetings and/or travel from AstraZeneca; and served in a leadership or fiduciary role as Board Director at Rare Voices Australia. Ian N. Bruce is a National Institute for Health Research (NIHR) Senior Investigator and is funded by the NIHR Manchester Biomedical Research Centre (NIHR 203308). His institution has received research grants from GSK and Genzyme/Sanofi and consultancy fees from GSK, UCB, Eli Lilly, BMS, Merck Serono, Aurinia and IL-TOO. Dr Bruce has received speaker fees from GSK, AstraZeneca and UCB; he also participated on a Data Safety Monitoring Board or Advisory Board for AstraZeneca and Merck Serono. Rangi Kandane-Rathnayake declares that there is no conflict of interest. Gudrun Weiss, Raj Tummala, and Hussein Al-Mossawi are all employees of and may hold stock in AstraZeneca. Alessandro Sorrentino is an employee of AstraZeneca and holds stock in Abbott, Galapagos, Gilead, and Moderna.

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