Purpose Long term immunosuppressive therapy (IST) in systemic lupus erythematosus (SLE) requires constant adjustment according to severity and organ involvement. This ongoing study aims to implement hydroxychloroquine therapy, reduce unnecessary IST, while achieving disease remission without worsening damage.

Methods A 3Rs strategy (Reduction, Replacement and Refinement) was implemented and therapy adjusted considering overall disease activity and safety profile. SLE patients from a single centre were followed between January 2013 and July 2017. Inclusion criteria: ACR criteria fulfilment; diagnosis from >1 year. Demographic and clinical features were registered at inclusion; SLEDAI-2K, therapy and flares recorded at inclusion and at each visit. SLICC damage index was calculated at inclusion and at the end. Data were analysed using SPSS.

Results At inclusion (n=79), 94% were females, median age 45 (IQR 36–57), mostly Caucasians (89%). Median disease duration was 13 (IQR 7–20). SLEDAI-2K at inclusion was <3 (inactive disease) in 63 (80%). Patients with active disease (SLEDAI-2K>3) at baseline were younger, with less disease duration, not enriched for a specific phenotype. Percentages of azathioprine and mycophenolate were reduced from 35 and 8 to 23 and 6, respectively, similar to interim results (39 months); hydroxychloroquine use remained >70% (10 discontinuations due to retinopathy). In contrast, steroids were steadily reduced from 68% to 42% and are now used at <6 mg/day in 22/33 patients. Importantly, steroid reduction or withdrawal rate was significantly higher in inactive disease group. Belimumab was maintained in 8 patients. Flare occurrence was higher in active disease patients (73% vs 17%, overall 27%). Most episodes were mild. Patients with flares were younger, with higher SLEDAI-2K and steroid dose at inclusion. No treatment discontinuation was associated with flare, except for azathioprine, mostly stopped due to safety profile. During the study, median SLICC damage index augmented from 0 to 1, frequently in the ophthalmological domain. Three patients died and ten were lost to follow-up from 39 to 54 months.

Conclusions The 3Rs strategy allowed to reduce unnecessary IST, especially in low disease activity group. Flares rates were in accordance to recent reports. In a long term perspective, our quest to reduce steroid burden seems promising.