Early Disease and Low Baseline Damage as Predictors of Response to Belimumab in Patients With Systemic Lupus Erythematosus in a Real‐Life Setting

Abstract

Objective. To investigate predictors of response, remission, low disease activity, damage, and drug discontinuation in patients with systemic lupus erythematosus (SLE) who were treated with belimumab.Methods. In this retrospective study of a multicenter cohort of SLE patients who received intravenous belimumab, the proportion of patients who achieved remission, low disease activity, and treatment response according to the SLE Responder Index 4 (SRI-4) was determined, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) was used to score disease damage yearly over the follow-up. Predictors of outcomes were analyzed by multivariate logistic regression with the results expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs).Results. The study included 466 patients with active SLE from 24 Italian centers, with a median follow-up period of 18 months (range 1-60 months). An SRI-4 response was achieved by 49.2%, 61.3%, 69.7%, 69.6%, and 66.7% of patients at 6, 12, 24, 36, and 48 months, respectively. Baseline predictors of response at 6 months included a score of ≥10 on the SLE Disease Activity Index 2000 (SLEDAI-2K) (OR 3.14 [95% CI 2.033-4.860]) and a disease duration of ≤2 years . Baseline predictors of response at 12 months included a score of ≥10 on the SLEDAI-2K (OR 3.48 [95% CI 2.004-6.025]) and an SDI score of 0 (OR 1.74 [95% CI 1.036-2.923]). Baseline predictors of response at 24 months included a score of ≥10 on the SLEDAI-2K (OR 4.25 [95% CI 2.018-8.940]) and a disease duration of ≤2 years (OR 3.79 [95% CI 1.039-13.52]). Baseline predictors of response at 36 months included a score of ≥10 on the SLEDAI-2K ) and baseline status of current smoker (OR 0.19 [95% CI 0.039-0.69]). Patients who were in remission for ≥25% of the follow-up period (44.3%) or who had low disease activity for ≥50% of the follow-up period (66.1%) accrued significantly less damage (P = 0.046 and P = 0.007). A baseline SDI score of 0 was an independent predictor of achieving low disease activity in ≥50% of the follow-up period and remission in ≥25% of the follow-up period. Our findings suggest that the lower the baseline damage, the greater the probability of achieving remission over the course of ≥25% of the follow-up. Further, there was a negative association between the number of flares reported prior to belimumab initiation and the frequency of belimumab discontinuation due to inefficacy (P = 0.009).Conclusion. In patients with active SLE and low damage at baseline, treatment with belimumab early in the disease may lead to favorable outcomes in a real-life setting.

Remission in systemic lupus erythematosus: testing different definitions in a large multicentre cohort

“…Since additional treatment is not always needed in patients with cSLEDAI=0 despite PGA ≥0.5, and since these items showed overlapping sensitivity, specificity, positive and negative predictive value against damage accrual (table 6 and figure 2), adding PGA <0.5 to cSLEDAI=0 could lead to overtreatment in controlled trials as well as in clinical practice when a treatto-target (T2T) approach is adopted. 21 In fact, T2T should aim at the most reachable target that positively influences patient prognosis. We observed that cSLEDAI=0 was the definition of remission easiest to achieve in real life, being able to predict damage accrual with a consistent degree of accuracy.…”

“…Therefore, a simplified remission definition based on cSLEDAI=0 can be reasonably used in observational studies where complete serological data, PGA and BILAG are not routinely assessed. 21 In the cSLEDAI=0 remission definition, the exclusion of a cut-off for PDN could imply that high dose glucocorticoids may mask disease activity, thus allowing patients not in real remission to be defined as remitted. Nevertheless, we found that adding PDN ≤5 mg/day to cSLEDAI=0 does not increase the performance against damage of cSLEDAI=0 in the short/medium term (5 years), as shown by the high overlap between confidence intervals.…”

Comparative analysis of long-term organ damage in patients with systemic lupus erythematosus using belimumab versus standard therapy: a post hoc longitudinal study

“…"It has been shown that belimumab may be more protective of long-term organ damage in patients with SLE with longer periods of remission or low disease activity." 6 This exploratory analysis suggested that belimumab plus standard therapy may slow the rate and magnitude of organ damage accrual compared with standard therapy alone. This analysis of a larger and more diverse US and non-US pooled population was consistent with our previously published US-focused study.…”

16 Targeting remission and low disease activity in SLE

“…Notably, biologics can help attain remission and LDA and, in turn, dampen damage progression. 9 Learning Objectives . Discuss the major targets in SLE management and their timing in a sequential strategy .…”