The analysis of five Phase III randomized controlled trials evaluating belimumab's effectiveness in SLE underscores its significant impact on disease management. Patient demographics, including sex, age, ancestry, disease duration, and clinical parameters such as SLEDAI-2K scores and anti-dsDNA antibody levels, exhibited no notable differences between treatment groups. 

Belimumab consistently surpassed placebo in improving mucocutaneous manifestations, as reflected in mcBILAG and mcSLEDAI-2K scores, with notable benefits observed as early as Week 12. Significant improvements in mcBILAG-based outcomes were evident from Week 12 onwards (OR: 1.29, 95% CI: 1.07–1.57, p = 0.008), while significant enhancements in mcSLEDAI-2K outcomes were noted from Week 16 (Week-52 OR: 1.37) 

Particularly noteworthy were the improvements seen in patients with baseline positive anti-dsDNA antibodies and higher disease activity (SLEDAI-2K scores ≥10). Subgroup analysis demonstrated even greater efficacy in these patient groups (Week 52 OR: 1.44 for anti-dsDNA antibodies; Week 52 OR: 1.49 for SLEDAI-2K scores ≥10). 

Moreover, belimumab exhibited sustained effectiveness in preventing disease flares, especially in patients with baseline positive anti-dsDNA antibodies. Notably, it also demonstrated efficacy in preventing mcBILAG flares in patients with positive anti-dsDNA antibodies and showed a trend towards significance in those with baseline SLEDAI-2K scores ≥10. 

These findings underscore belimumab's therapeutic benefits in enhancing disease control and preventing flares among specific subsets of SLE patients, highlighting its potential as a personalized treatment option for severe disease manifestations.

KOL insights

“This post hoc analysis showed fewer patients experienced flares with belimumab versus placebo in the pooled population and in early or established disease subgroups, with particular benefit suggested in patients with no baseline organ damage. The proportion of patients with flares was lower in those with early versus established disease, for belimumab and placebo.” – Expert Opinion

Conclusion

The total diagnosed prevalent cases of SLE in the United States were around 515,450 cases in 2023. The recent approvals of voclosporin, belimumab, and other biological disease-modifying antirheumatic drugs (DMARDs) present an opportunity to enhance long-term renal outcomes. These new treatments also help address the issues commonly associated with conventional immunosuppressants, such as poor tolerance, low adherence to medication, high rates of disease flares, and cumulative steroid toxicity. 

BENLYSTA (belimumab), a B-lymphocyte stimulator specific inhibitor received its first approval in the year 2011 for adult patients suffering from SLE and receiving standard therapy. Recently, in 2024, the drug received US FDA approval for its 200 mg subcutaneous autoinjector for patients five years of age and older with active SLE. As per DelveInsight, BENLYSTA is expected to capture ~USD 980 million by 2034 in the US. Sales of BENLYSTA are expected to decline after 2025 due to the expiration of its patent in the United States in 2025 and in Europe in 2026.

In this retrospective analysis of five randomized controlled trials, belimumab demonstrates superiority over placebo in eliciting a treatment response and reducing flares in the mucocutaneous aspects of SLE, particularly among patients presenting with significant disease activity and active disease at baseline. These findings emphasize belimumab's effectiveness in personalized treatment strategies for SLE, offering enhanced benefits tailored to specific patient subgroups.