Concept and development of glucocorticoid application in systemic lupus erythematosus under treat-to-target strategy

Glucocorticoids (hormones for short) act in two main ways: the genomic pathway, which is the main effective pathway for oral glucocorticoids, and the non-genomic pathway, which is activated at doses of up to 100 mg/day of prednisone. Hormones have been considered as a "double-edged sword" in the treatment of SLE: on the one hand, they exert rapid and powerful anti-inflammatory and immunosuppressive effects, while on the other hand, their long-term accumulation leads to the irreversible organ damage accrual. To date, glucocorticoids remain the most critical first-line drug in the management of SLE due to the lack of safer and more effective treatments. Recent studies have shown that the long-term accumulation of glucocorticoids doses and challenges in dose reduction have become the primary barrier for target achievement in SLE treat-to-target therapy. Current research evidence suggests that longer duration of disease stabilization, more stable disease activity status, and better maintenance therapeutic regimens are key to achieving successful glucocorticoids taper. Glucocorticoids pulse can activate non-genomic effect pathways that on the one hand induce rapid disease remission without significantly increasing side effects, and on the other hand create opportunities for lower initial doses of oral glucocorticoids and rapid dose reduction. Drugs such as hydroxychloroquine, immunosuppressants, small-molecule targeted agents, and biologics are also able to help glucocorticoids dose reduction. In addition, the development of new drugs including selective glucocorticoids receptor agonists may be able to play a greater role in the future. In conclusion, how to achieve successful glucocorticoids reduction and eventual discontinuation while maintaining stable disease control has become an increasingly important topic in SLE, and more high-quality evidence-based medical evidence is needed.