Long-term treatment with belimumab slows the key drivers of organ damage — disease activity, severe flares, and glucocorticoid exposure — in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) compared with background therapy alone, according to the authors of a new literature review.

SLE most commonly affects the cardiovascular, neuropsychiatric, musculoskeletal, and renal systems. Up to 80% of organ damage is attributable to glucocorticoid exposure, but other SLE therapies may also contribute, investigators noted. Risk factors also include dyslipidemia, hypertension, older age, male sex, and Black or Hispanic race.

Across 4 randomized controlled SLE BLISS trials, 52 weeks of add-on treatment with belimumab significantly increased the probability of SLE Responder Index (SRI-4) by 54%, 68%, 83%, and 99% compared with background therapy alone, Michelle Petri, MD, MPH, of Johns Hopkins University School of Medicine, Baltimore, Maryland, and colleagues reported in Arthritis Care & Research. This was sometimes accompanied by a decreased risk of severe flares and reduced glucocorticoid use.

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The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI) is a validated measure that assesses cumulative damage across multiple organs. Ideally, randomized trials lasting 5 or more years are needed to directly assess the effects of therapy on SDI, but are not often feasible, the investigators noted. Open-label extension and propensity-score matching analysis studies of patients with SLE treated with belimumab suggested decreased risk of organ damage progression compared with standard care. In GSK201223, 85.1% of patients receiving belimumab had no change in SDI score from baseline, the reviewers reported. In a separate, propensity-score matched analysis, belimumab treatment was associated with a 61% reduction in the risk of progressing to a higher SDI score during follow-up, compared with background therapy.

Finally, in a post hoc analysis of BLISS-LN, belimumab was associated with a 50% reduction in the risk for a renal-related event or death in patients with LN. Flare risk decreased 55% after week 24. Slower decline in estimated glomerular filtration rate also occurred with belimumab.

“These observed impacts of belimumab on organ damage imply a disease-modifying effect on SLE, including LN, suggesting potential benefits of belimumab treatment earlier in the disease course,” Dr Petri’s team wrote.

Disclosure: This research was supported by GlaxoSmithKline. Please see the original reference for a full list of disclosures.

Reference

Urowitz MB, Aranow C, Asukai Y, et al. Impact of belimumab on organ damage in systemic lupus erythematosus. Arthritis Care Res. Published online April 19, 2022. doi:10.1002/acr.24901