Safety and efficacy of intravenous belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial

Abstract

ObjectivesThis ongoing Phase-2, randomised, placebo-controlled, double-blind study evaluated the efficacy, safety and pharmacokinetics of intravenous belimumab in childhood-onset systemic lupus erythematosus (cSLE).MethodsPatients (5 to 17 years) were randomised to belimumab 10 mg/kg intravenous or placebo every 4 weeks, plus standard SLE therapy. Primary endpoint: SLE Responder Index (SRI4) response rate (Week 52). Key major secondary endpoints: proportion of patients achieving the Paediatric Rheumatology International Trials Organisation/American College of Rheumatology (PRINTO/ACR) response using 50 and ‘30 alternative’ definitions (Week 52), and sustained response (Weeks 44 to 52) by SRI4 and Parent Global Assessment of well-being (Parent-global). Safety and pharmacokinetics were assessed. Study not powered for statistical testing.ResultsNinety-three patients were randomised (belimumab, n=53; placebo, n=40). At Week 52, there were numerically more SRI4 responders with belimumab versus placebo (52.8% vs 43.6%; OR 1.49 (95% CI 0.64 to 3.46)). PRINTO/ACR 30 alternative (52.8% vs 27.5%; OR 2.92 (95% CI 1.19 to 7.17)) and PRINTO/ACR 50 (60.4% vs 35.0%; OR 2.74 (95% CI 1.15 to 6.54)) responses were more frequent with belimumab than placebo, as were sustained responses for SRI4 (belimumab, 43.4%; placebo, 41.0%; OR 1.08 (95% CI 0.46 to 2.52)) and Parent-global (belimumab, 59.1%; placebo, 33.3%; OR 3.49 (95% CI 1.23 to 9.91)). Serious adverse events were reported in 17.0% of belimumab patients and 35.0% of placebo patients; one death occurred (placebo). Week-52, geometric mean (95% CI) belimumab trough concentration was 56.2 (45.2 to 69.8) µg/mL.ConclusionThe belimumab intravenous pharmacokinetics and benefit–risk profile in cSLE are consistent with adult belimumab studies and the 10 mg/kg every 4 weeks dose is appropriate.Trial registration numberNCT01649765.

Systemic Lupus Erythematosus in Children and Young People

“…Very recently, the first trial of intravenous belimumab in active jSLE, the PLUTO study, assessed intravenous belimumab (10 mg/kg), plus standard jSLE therapy versus placebo in 93 jSLE patients. At week 52, a numerically higher proportion of patients receiving belimumab met the primary endpoint of SLE Responder Index 4 (SRI4, 52.8% vs. 43.6%; OR 1.49 (95% CI 0.64 to 3.46)); however, the CI crossed 1 [ 126 ]. SRI4 is the primary outcome measure that was used in the original adult-onset SLE Belimumab trial.…”

“…A significantly higher proportion of belimumab-treated patients achieved both the PRINTO/ACR 30 (52.8% vs. 27.5%; OR 2.92 (95% CI 1.19 to 7.17)) and PRINTO/ACR 50 (60.4% vs. 35.0%; OR 2.74 (95% CI 1.15 to 6.54)) responses. A sustained SRI4 response was not achieved, but there was a significant improvement in the parent-global score [ 126 ]. The present study raises important questions about the applicability of adult SLE outcome measures in jSLE, given the known differences in disease activity, severity and damage demonstrated between paediatric, adolescent and adult SLE [ 11 , 12 , 128 ].…”

Emerging B-Cell Therapies in Systemic Lupus Erythematosus

“…There were no additional safety signals noted in the PLUTO trial. 46 Of note, there was one death in the placebo group and none in the belimumab group. There were no malignancies noted in either group during the trial.…”

“… EMBRACE 47 Did not meet primary endpoint for treatment of SLE with intravenous form in Black patients. Approved for treatment of SLE in patients aged 5–17 years in 2019 PLUTO 46 Combined phase II/III trial in pediatric lupus using intra-venous form. Over 50% of the children met the primary endpoint.…”

“…PLUTO is an ongoing, combined Phase II and III double-blind placebo-controlled, randomized trial of the use of intravenous belimumab at 10mg/kg/dose once every 4 weeks in pediatric SLE. 46 PLUTO randomized 53 pediatric SLE patients to treatment with belimumab plus SOC medications, and 40 patients to be given placebo plus SOC medications. Although this trial was not designed or powered to have significance, given the relative rarity of pediatric SLE, 53% of the children with SLE treated with belimumab met the primary endpoint of SRI-4 response at 52 weeks, as compared to 44% of the children given placebo.…”