Belimumab yields earlier renal response, steroid tapering in childhood lupus nephritis
Key takeaways:
- Children treated with belimumab were more likely to achieve primary efficacy renal response vs. standard immunotherapy.
- Lower glucocorticoid dosages were significantly more common with belimumab.
Children with lupus nephritis who receive belimumab achieve treatment targets faster, and can taper glucocorticoids earlier, than those using standard immunotherapy, according to data published in Lupus Science & Medicine.
“With the continuous advance of the pathogenesis of [systemic lupus erythematosus (SLE)]/[lupus nephritis], new medications such as belimumab have been developed and applied in clinical practice,” Yinv Gong, of the department of rheumatology at the Children’s Hospital of Fudan University, in Shanghai, and colleagues wrote. “The phase 3 clinical trials of belimumab in adult SLE (Belimumab in Subjects with Systemic Lupus Erythematosus (BLISS)-52, BLISS-76) conducted in 2011 demonstrated the efficacy and safety of belimumab combined with standard immunotherapy.
“In 2020, the clinical trials of belimumab for active LN (BLISS-LN) and active [childhood-onset SLE (cSLE)] (The Pediatric Lupus Trial of Belimumab Plus Background Standard Therapy (PLUTO)) were published, indicating similar benefits and safety results in adult LN and active cSLE,” they added. “However, few cohort studies reported on the use of belimumab in childhood-onset lupus nephritis.”
To assess the efficacy of belimumab (Benlysta, GlaxoSmithKline) for the initial treatment of newly diagnosed childhood-onset lupus nephritis, Gong and colleagues conducted a retrospective study of children admitted to the Children’s Hospital of Fudan University from January 2016 through December 2022. The researchers compared the outcomes of 63 patients who received only standard immunotherapies — defined as glucocorticoids, hydroxychloroquine, cyclophosphamide, mycophenolate mofetil, tacrolimus, or a combination of the latter two — with those of 38 patients also treated with belimumab.
Patients in the belimumab group received a dose of 10 mg/kg once every other week for 4 weeks, then once every 4 weeks. The primary outcome was 12-month primary efficacy renal response, defined as urine protein-to-creatinine ratio of 0.7 mg/mg or lower; at least 20% decrease in estimated glomerular filtration rate (eGFR), or eGFR of at least 60 mL/min/1.73 m2; and no treatment failure resulting in rescue therapy.
According to the researchers, more patients with childhood lupus nephritis treated with belimumab achieved the primary outcome (97.1%) than those treated with only standard immunotherapy (80%) (P = .046). Patients in the belimumab group outpaced those on standard immunotherapy as early as 3 months in meeting the primary outcome and were more likely to sustain it through 24 months (HR = 0.631; 95% CI, 0.415-0.959).
Patients treated with belimumab also demonstrated lower glucocorticoid dosages over time. At 12 months, 82.9% of belimumab-treated patients had glucocorticoid dosages below 7.5 mg per day compared with 30.4% of those on standard immunotherapy. For 5 mg per day, those percentages were 42.9% and 19.6%, respectively.
There were no serious infections in either group, while varying degrees of infection were reported by 60.5% of the belimumab group and 61.9% of the standard immunotherapy group.
“The strategy of initial combination with belimumab helps to improve early response rates within the ‘window of opportunity,’ minimizing glomerular loss and [glucocorticoid] dose as much as possible,” Gong and colleagues wrote. “Additionally, initial combination therapy may yield more significant benefits in children with high disease activity in [childhood lupus nephritis]. The upfront combination (step down) strategy is more suitable in cSLE/lupus nephritis.”
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