Treat-to-target in systemic lupus erythematosus: advancing towards its implementation

• Published in: Nature reviews. Rheumatology Vol. 18; no. 3; pp. 146 - 157
• Main Authors: Parra Sánchez, Agner R., Voskuyl, Alexandre E., van Vollenhoven, Ronald F.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2022; Nature Publishing Group
• Subjects: 692/308/409; 692/4023/1670/1613; 692/700/565; Diabetes mellitus; Lupus; Medicine; Medicine & Public Health; Patients; Remission; Review Article; Rheumatoid arthritis; Rheumatology; Systemic lupus erythematosus
• ISSN: 1759-4790; 1759-4804
• DOI: 10.1038/s41584-021-00739-3

The treat-to-target (T2T) concept has improved outcomes for patients with diabetes, hypertension and rheumatoid arthritis. This therapeutic strategy involves choosing a well-defined, relevant target, taking therapeutic steps, evaluating whether the target has been achieved, and taking action if it has not. The T2T principle has been embraced by systemic lupus erythematosus (SLE) experts, but measurable and achievable outcomes, and therapeutic options, are needed to make this approach possible in practice. Considerable evidence has been generated regarding meaningful ‘state’ outcomes for SLE. Low disease activity has been defined and studied, and the most aspirational goal, remission, has been defined by the Definition of Remission in SLE task force. By contrast, current therapeutic options in SLE are limited, and more effective and safer therapies are urgently needed. Fortunately, clinical trial activity in SLE has been unprecedented, and encouraging results have been seen for novel therapies, including biologic and small-molecule agents. Thus, with the expected advent of such treatments, it is likely that sufficiently diverse therapies for SLE will be available in the foreseeable future, allowing the routine implementation of T2T approaches in the care of patients with SLE. This Review discusses progress in identifying potential outcome measures and developing treatment options to achieve a treat-to-target approach in systemic lupus erythematosus, as well as the research advances that are needed to realize these objectives. Key points The treat-to-target (T2T) therapeutic strategy consists of four key steps: establish a relevant individualized target, take steps to achieve it, monitor the target achievement, and adjust the therapy if the target is not achieved. Validation of the Lupus Low Disease Activity State (LLDAS) definition of low disease activity and recent consensus on the final DORIS definition of remission in systemic lupus erythematosus (SLE) have provided feasible treatment targets for the adoption of a T2T strategy in SLE. With the advent of novel therapeutics for SLE, including biologics and small molecules, T2T for SLE will become a clinical reality in the coming years. The use of LLDAS and DORIS definitions in clinical trials for novel therapeutics could provide robust, discriminatory outcome measures. Trials comparing the active attainment of LLDAS or DORIS remission as end points in a T2T approach with a conventional management approach are still needed.