Belimumab Shows Efficacy for Mucocutaneous Symptoms in SLE

TOPLINE: 

Belimumab combined with standard therapy demonstrated significant improvements in mucocutaneous symptoms in patients with systemic lupus erythematosus (SLE) compared with placebo with standard therapy, with benefits maintained through week 52. Patients with high disease activity and serological activity at baseline showed considerable improvement.

METHODOLOGY:

• Researchers conducted a post hoc analysis of data from five phase 3 clinical trials to assess belimumab’s impact on mucocutaneous manifestations of SLE.
• The study included 3086 patients (mean age, 37 years; 94.4% women) who met the American College of Rheumatology criteria for SLE classification and had an ANA titre ≥ 1:80 and/or serum anti-dsDNA antibody level ≥ 30 IU/mL and a Safety of Estrogens in Lupus National Assessment SLE Disease Activity Index (SLEDAI) score ≥ 6 or 8 at screening.
• Participants received either belimumab (n = 1087) or placebo (n = 752) in addition to standard therapy upon randomisation, with belimumab administered intravenously (1 mg/kg or 10 mg/kg at baseline, 2 weeks, and 4 weeks, and thereafter every fourth week) or subcutaneously (200 mg/week) depending on the trial.
• Mucocutaneous SLE disease activity was evaluated using the mucocutaneous domain of the British Isles Lupus Assessment Group (mcBILAG) index and the mucocutaneous domain of the SLE Disease Activity Index 2000 (mcSLEDAI-2K), with assessments done every 4 weeks.
• Improvement was defined as a change in mcBILAG scores from A at baseline to B or from B at baseline to C, D, or E, along with a reduction in mcSLEDAI-2K scores of ≥ 2 points from baseline, with sustained improvement defined as improvement persisting for at least two consecutive visits and maintained through week 52. Flares were assessed and defined as worsening of mcBILAG scores from B, C, D, or E at baseline to A or from C, D, or E at baseline to B.

TAKEAWAY:

• Belimumab plus standard therapy was more effective than placebo plus standard therapy in inducing improvement in mucocutaneous symptoms (mcBILAG-based improvement), with effects first observed at 12 weeks (odds ratio [OR], 1.28; P = .012) and sustained at 52 weeks (OR, 1.29; P = .008). mcSLEDAI-2K-based improvement was first noted at week 16 (OR, 1.20; P = .025), with significant improvement at week 52 as well (OR, 1.37; P < .001).
• Patients with high disease activity (SLEDAI-2K ≥ 10) showed greater improvement with belimumab than with placebo at week 52 (OR, 1.49; P = .001 for mcBILAG-based improvement and OR, 1.49; P < .001 for mcSLEDAI-2K–based improvement).
• Patients with positive anti-dsDNA levels at baseline benefitted significantly with belimumab vs placebo at week 52, with both mcBILAG- and mcSLEDAI-2K-based improvements observed. Compared with placebo, belimumab also prevented mucocutaneous flares in patients with positive anti-dsDNA levels (hazard ratio [HR], 0.70; P = .035).
• Patients on belimumab vs placebo showed sustained improvements in mcBILAG (HR, 1.23; P = .003) and mcSLEDAI-2K (HR, 1.24; P < .001) through week 52, which were also noted in those with high disease activity or positive anti-dsDNA levels at baseline (P < .001 for all).

IN PRACTICE:

“These findings justify the use of belimumab for treating mucocutaneous manifestations of SLE, with improvements expected from 3 months and resolution of symptoms from 4 months upon treatment commencement,” the authors wrote.

SOURCE:

The study was led by Ioannis Parodis, Karolinska Institutet, Stockholm, Sweden. It was published online on March 14, 2025, in Rheumatology.

LIMITATIONS: 

The trials were not specifically designed to assess belimumab’s efficacy across different organ systems. The eligibility criteria for participants were trial specific and may have introduced selection bias, limiting applicability to real-world SLE populations. The absence of the Cutaneous Lupus erythematosus disease Area and Severity Index in the trials limited detailed characterisation of mucocutaneous involvement, preventing differentiation between specific subsets of cutaneous involvement or isolated mucosal involvement.

DISCLOSURES:

The study was supported by grants from the Swedish Rheumatism Association, King Gustaf V’s 80-year Foundation, Swedish Society of Medicine, Nyckelfonden, Professor Nanna Svartz Foundation, Ulla and Roland Gustafsson Foundation, Region Stockholm, and Karolinska Institutet. One author disclosed receiving research funding and/or honoraria from multiple pharmaceutical companies, including Amgen, AstraZeneca, and GSK.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.