LAUSR

In Italy, the use of belimumab has been authorized since 2013, in patients with active systemic lupus erythematosus (SLE) with positive anti–double-stranded DNA and low C3 or C4 levels, despite standard therapy. Belimumab is effective in reducing disease activity and number of flares and in blocking damage progression. To our knowledge, no data are available on dose tapering of belimumab in SLE patients chronically treated with it.The aim of this retrospective study was to analyse prevalence of tapering in a single cohort and to evaluate disease activity after tapering.Patients, who received intravenous belimumab (10mg/kg) for at least 12 months between June 2013 and December 2020 were enrolled. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC-SDI), Physician Global Assessment (PGA), C3 and C4 levels, and prednisone daily dose were recorded at baseline and every six-months. Follow-up was stopped when patients switched to subcutaneous belimumab or when it was discontinued for more than 6 months (interrupted). Dose tapering was defined as the prolongation of the regular dose interval, after initial treatment based on the registered dosage.Between June 2013 and December 2020, 48 patients received intravenous belimumab for at least 12 months (100% Caucasians, 94% females). All patients received standard belimumab dosage of 10mg/Kg every 4 weeks. Fourteen (29.1%) of 48 patients lengthened the dosing interval to 5 weeks; a subsequent lengthening of the interval occurred in 7 patients every 6 weeks and in 1 patient belimumab was gradually tapered to every 13 weeks.Twelve months (T12) after belimumab introduction, 3 patients (6.2%) were receiving a tapered dosage; at T24, 9 out of the 37 (24.3%), at T36 9 out of 21 (42.8%), and at T48 8 out of 18 (44.4%). Differences in disease activity, damage, concomitant medications, disease duration at belimumab introduction (baseline) were evaluated among patients that maintained the standard interval versus the group that received a tapered dose. Notably, no differences were found among the two groups (standard dose vs tapering) concerning median age at baseline (41, IQR 31-47.5 vs 38, IQR 32.2-51.5), disease duration (median 11, IQR 7.2-16 vs 9, IQR 5.5-14.5), median prednisone daily dosage (7.1mg, IQR 5-11.9 versus 11mg, IQR 7.6-17.5) and median SLEDAI-2K (8, IQR 6-9.75 vs 8, IQR 5-10). Differences in concomitant medications or clinical manifestations are reported in Figure 1A.Among the group that received the standard dose, 7 patients discontinued the treatment (20.6%), specifically 2 renal flares and one adverse event occurred. Whereas, in the reduced dose group, 2 discontinuations occurred (14.3%) due to a pregnancy and a renal flare. Noteworthy, the patient with the renal flare resumed subcutaneous belimumab 12 months after the flare. Finally, the disease activity was analysed in the 12 months after the first drug reduction (Figure 1B-E), with no sign of worsening of evaluated parameters (Figure 1B-1E), but with a significant reduction of steroids and SLEDAI-2K, 6 months after tapering.In our single retrospective cohort, we have demonstrated that belimumab tapering seems to be safe and not associated with a worsening disease activity over the following months. However, further studies are required to identify eligibility criteria and to determine the optimal dose-tapering strategy both for the intravenous and the subcutaneous formulations.Figure 1.None declared