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

<jats:sec><jats:title>Objective</jats:title><jats:p>To investigate predictors of response, remission, low disease activity, damage, and drug discontinuation in patients with systemic lupus erythematosus (<jats:styled-content style="fixed-case">SLE</jats:styled-content>) who were treated with belimumab.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In this retrospective study of a multicenter cohort of <jats:styled-content style="fixed-case">SLE</jats:styled-content> patients who received intravenous belimumab, the proportion of patients who achieved remission, low disease activity, and treatment response according to the <jats:styled-content style="fixed-case">SLE</jats:styled-content> Responder Index 4 (<jats:styled-content style="fixed-case">SRI</jats:styled-content>‐4) was determined, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (<jats:styled-content style="fixed-case">SDI</jats:styled-content>) 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 (<jats:styled-content style="fixed-case">OR</jats:styled-content>s) and 95% confidence intervals (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>s).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The study included 466 patients with active <jats:styled-content style="fixed-case">SLE</jats:styled-content> from 24 Italian centers, with a median follow‐up period of 18 months (range 1–60 months). An <jats:styled-content style="fixed-case">SRI</jats:styled-content>‐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 <jats:styled-content style="fixed-case">SLE</jats:styled-content> Disease Activity Index 2000 (<jats:styled-content style="fixed-case">SLEDAI</jats:styled-content>‐2K) (<jats:styled-content style="fixed-case">OR</jats:styled-content> 3.14 [95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 2.033–4.860]) and a disease duration of ≤2 years (<jats:styled-content style="fixed-case">OR</jats:styled-content> 1.94 [95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 1.078‐3.473). Baseline predictors of response at 12 months included a score of ≥10 on the <jats:styled-content style="fixed-case">SLEDAI</jats:styled-content>‐2K (<jats:styled-content style="fixed-case">OR</jats:styled-content> 3.48 [95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 2.004–6.025]) and an <jats:styled-content style="fixed-case">SDI</jats:styled-content> score of 0 (<jats:styled-content style="fixed-case">OR</jats:styled-content> 1.74 [95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 1.036–2.923]). Baseline predictors of response at 24 months included a score of ≥10 on the <jats:styled-content style="fixed-case">SLEDAI</jats:styled-content>‐2K (<jats:styled-content style="fixed-case">OR</jats:styled-content> 4.25 [95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 2.018–8.940]) and a disease duration of ≤2 years (<jats:styled-content style="fixed-case">OR</jats:styled-content> 3.79 [95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 1.039–13.52]). Baseline predictors of response at 36 months included a score of ≥10 on the <jats:styled-content style="fixed-case">SLEDAI</jats:styled-content>‐2K (<jats:styled-content style="fixed-case">OR</jats:styled-content> 14.59 [95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 3.54–59.79) and baseline status of current smoker (<jats:styled-content style="fixed-case">OR</jats:styled-content> 0.19 [95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 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 (<jats:italic>P</jats:italic> = 0.046 and <jats:italic>P</jats:italic> = 0.007). A baseline <jats:styled-content style="fixed-case">SDI</jats:styled-content> 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 (<jats:italic>P</jats:italic> = 0.009).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>In patients with active <jats:styled-content style="fixed-case">SLE</jats:styled-content> and low damage at baseline, treatment with belimumab early in the disease may lead to favorable outcomes in a real‐life setting.</jats:p></jats:sec>