Targeting DORIS Remission and LLDAS in SLE: A Review

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. 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.