Benefits of Early Belimumab Intervention in SLE, with Karen Costenbader, MD

In an interview with HCPLive,Karen Costenbader, MD, director of the Lupus Program at Brigham and Women’s Hospital, gives an overview of 2 analyses that demonstrated treatment with belimumab reduces flares and increases Systemic Lupus Erythematosus Responder Index 4 (SRI-4) response rates among patients with early active systemic lupus erythematosus (SLE). Findings were presented at the 2024 European Congress of Rheumatology (EULAR) conference.

The recent secondary analyses of data from 5 major belimumab trials have provided significant insights. These outcomes, collected during the trials but not previously analyzed in this manner, are considered robust despite being post-hoc analyses.

When belimumab received US Food and Drug Administration (FDA) approval in 2011, the principal approach was to reserve biologic medications until patients had failed other treatments due to uncertainties about long-term effects and insurance constraints. Typically, patients would first try hydroxychloroquine, non-steroidal anti-inflammatory drugs, and steroids, followed by traditional immunosuppressants like methotrexate and mycophenolate. Only after these failed would biologics like belimumab be considered.

However, Costenbader explained that as evidence of belimumab’s effectiveness emerged, clinicians began using it earlier. Yet, many insurance companies and treatment paradigms still mandated that biologics be used only after other treatments had failed, allowing disease flares and damage to persist. Now, there is a paradigm shift towards treating lupus earlier to prevent flares and damage and achieve low disease activity sooner.

The 2 abstracts analyzed data from 3,086 patients across the 5 trials conducted by GSK. Patients were randomized to receive either belimumab (n = 1,869) or placebo (n = 1,217). The analyses stratified patients by early versus later disease stages, a classification not predefined but driven by a renewed focus on early treatment. The updated EULAR guidelines also advocate for earlier biologic use in severe disease cases, alongside immunosuppressants.

Early disease in these studies was defined by a lupus duration of < 2 years at trial start, no baseline organ damage, and no prior use of other immunosuppressants. Among the participants, 29% had early disease, 66% had no organ damage at entry, and 47% had not used other immunosuppressants.

The primary outcome measured was the SRI-4 response, a composite index of lupus disease activity reduction, which includes a reduction in the systemic lupus erythematosus disease activity index (SLEDAI) score by ≥ 4 points, no new British Isles Lupus Assessment Group (BILAG), and no worsening of the physician global assessment. Results showed that belimumab was effective in both early and later disease stages, with better responses observed in earlier treatment.

Additionally, earlier use of belimumab significantly reduced the number of disease flares, which is clinically crucial as each flare can lead to irreversible organ damage. The findings underscore the importance of early intervention in improving quality of life and preventing long-term damage in lupus patients.

Disclosures: Costenbader is associated with GSK, BMS, AstraZeneca, Cabaletta Bio, Exagen Diagnostics, Merck, and Gilead.