Reducing Dose of Belimumab in Patients with Lupus

Mithu Maheswaranathan, MD

Credit: Duke Health

Belimumab is an anti-B-cell activating factor (BAFF) monoclonal antibody and biologic therapy commonly used in the treatment of systemic lupus erythematosus (SLE). While uncommon, belimumab has potential adverse effects like infection and has a high cost relative to other conventional synthetic disease-modifying antirheumatic drug (DMARD) therapy. In this new article in Rheumatology, Rua-Figueroa et al report results of their study investigating impact of reduced dose of belimumab in SLE, based on evidence from meta-analyses of randomized clinical trials suggesting possible efficacy of doses lower than those recommended in the approved dosing (10mg/kg IV every 4 weeks or 200mg SQ every week).1

This was a retrospective cohort study of patients with SLE on belimumab in multiple centers in Spain. Patients who met American College of Rheumatology (ACR) criteria for SLE previously treated with IV or SQ Benlysta in a clinical setting were enrolled. Demographic characteristics, disease activity using Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and Physician Global Assessment (PGA) were obtained. Laboratory parameters collected included basic labs, urinalysis, dsDNA antibodies, and complement levels (C3/C4).The authors used the Definition of Remission in SLE (DORIS) 2021 for remission and the Lupus Low Disease Activity State (LLDAS) for low disease activity. Organ damage was assessed using the Systemic Lupus International Collaborating Clinics (SLICC)/ACR Damage Index (SDI); damage was evaluated at baseline, at 12 months, and the last visit.

The study included 324 patients with SLE treated with belimumab, with median duration of follow-up under belimumab treatment of 3.2 years. The belimumab dose was reduced in around 9% of the cohort (n = 29/324). All patients on SQ BEL had the administration interval increased from 7 days to 10-21 days. For patients on IV BEL administration, some received a reduced dose every 4 weeks (ranging 5-8mg/kg) and others received an extended interval to every 5 or 6 weeks.At the pre-reduction evaluation, 15 patients (around 58%) were taking DMARDs concomitantly with belimumab and similarly 58% were taking glucocorticoids. The median baseline PGA was .33 and median baseline SLEDAI was 0; a total of nearly 58% of patients were in remission according to 2021 DORIS and 88.5% in low-disease activity state (LLDAS) at baseline.

Following the belimumab dose reduction, at 6 months after reduction, approximately 58% and 81% of patients were in remission according to 2021 DORIS definition and LLDAS, respectively.At 12 months, the percentages increased to 67% and 90%. There were no statistically significant differences in the proportion of patients who lost DORIS or LLDAS status, and no significant difference in disease activity by SLEDAI. There was a statistically significant difference in complement levels, with more patients having low complements at 6 and 12 months. However, the changes in serologic activity did not lead to relevant or significant changes in therapy.

Ultimately, this study provides some evidence of the ability to potentially reduce belimumab dose in a subset of patients with SLE, particularly those with more quiescent disease activity.While a significant change in serologic activity (complement levels) was observed post-belimumab reduction, there were no changes in treatment. There are several limitations including patients all from one country (unclear generalizability), small sample size, and retrospective study design with its inherent biases and limitations. Additionally, there were no patients with lupus nephritis; thus, whether results are applicable to those with SLE nephritis or more severe disease is unknown, and the precise durability of these results long-term is also uncertain.

However, this study suggests a proportion of patients with non-renal SLE can have reduction in belimumab dose with no significant increase or worsening of their clinical disease activity.

References

1. ^{Rua-Figueroa I, Altabás-González I, Mouriño C, et al. Can the Dose of Belimumab be Reduced in Patients with Systemic Lupus Erythematosus?. Rheumatology (Oxford), May 2024 online. doi:10.1093/rheumatology/keae270}