Systemic lupus erythematosus (SLE) is a lifelong disease with a median onset age of 15-44 years.¹ As continued treatment with glucocorticoids (GCs) and immunosuppressive therapies can contribute to damage accrual, tapering of treatment is inevitable during the course of the disease.¹ However, this can also lead to an increased risk of flares, which may be lower if the patient has a longer cumulative duration of stable disease prior to tapering.¹ During the EULAR 2024 Congress, Dr. Jiacai Cho from the National University Hospital, Singapore, presented the results from a large multinational cohort study on behalf of the Asia Pacific Lupus Collaboration, which investigated whether tapering of immunosuppressive therapy or GCs among stable SLE patients impacts damage accrual.¹

In this study, patients who fulfilled the American College of Rheumatology (ACR) or Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) criteria for SLE were recruited from 13 Asia-Pacific countries prospectively between 2013-2020.¹ The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and physician global assessment (PGA) scores were collected at each visit (every 1-6 months), as well as the SLICC Damage Index (SDI) annually.¹ The first visit during which the patient achieved target (low disease activity [SLEDAI≤4, PGA≤1, prednisolone ≤7.5mg/day], clinical remission [cSLEDAI=0, PGA<0.5, prednisolone ≤5mg/day], or complete remission [SLEDAI=0, PGA<0.5, prednisolone ≤5mg/day]) was recorded, and all consecutive visits that continued to be in target were included into a “period”.¹ The researchers then determined whether tapering had occurred in each of these periods, defined as any decrease in the dose of GCs or immunosuppressive therapy (mycophenolate mofetil, cyclosporine, azathioprine, leflunomide, methotrexate or tacrolimus).¹ Multivariable Cox regression models were then performed to analyze the time to first increase in SDI after achieving stable disease targets among patients who received corticosteroid and/or immunosuppressive therapy tapering versus those who received continuous therapy.¹ Flares, corticosteroid tapering and immunosuppressive therapy tapering were fitted as separate time-dependent covariates.¹

In total, 2,472 patients in LLDAS (lupus low disease activity state) or remission were analyzed, with a mean age of 42 years (standard deviation [SD]=13.7), mean SLEADAI-2K OF 1.8 (SD=1.6), and baseline damage in 829 (33.5%) patients.¹ Among these patients, 49.7% (n=1,228) had treatment tapering, whereas the rest (n=1,244) did not taper.¹ Flares, defined using the SELENA-SLEDAI flare index (SFI), occurred in 48.6% (n=597) of patients who had tapering, compared with 33.9% (n=422) of patients who received continuous therapy.¹ 21.8% (n=268) of those who had tapering experienced new damage compared to 13.7% (n=170) of those who did not taper.¹ The multivariable models showed that age (hazard ratio [HR]=1.04; 95% CI: 1.03-1.04; p<0.001), SDI score at first stable visit (HR=1.15; 95% CI: 1.06-1.24; p<0.001), flares (HR=1.29; 95% CI: 1.04-1.61; p=0.023), and higher prednisolone dose (5mg/day-7.5mg/day compared to 0mg/day) at first stable visit (HR=1.90; 95% CI: 1.38-2.62; p<0.001) were significantly associated with higher hazards of accruing new damage.¹ While GC tapering was not significantly associated with damage accrual (HR=0.84; 95% CI: 0.66-1.07; p=0.166), immunosuppressive therapy tapering was associated with increased damage accrual (HR=1.56; 95% CI: 1.21-2.02; p<0.001).¹ Interaction terms between tapering of immunosuppressive therapy with tapering of GCs or with baseline SDI score were not statistically significant.¹

In conclusion, a substantial proportion of SLE patients who achieved LLDAS and complete remission still experienced incident flares and damage.¹ In stable disease, tapering of immunosuppressive therapy, but not GCs, was independently associated with increased damage accrual.¹ This may suggest an under-evaluated protective effect of immunosuppressive therapies against incident damage even in stable disease.¹ Moreover, SLEDAI-2K, PGA, and SFI may not encompass global disease activity for all patients.¹ Tapering should thus be exercised only after carefully selecting the correct patient and timing.¹