RT Journal Article
SR Electronic
T1 Safety and efficacy of intravenous belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1340
OP 1348
DO 10.1136/annrheumdis-2020-217101
VO 79
IS 10
A1 Hermine I Brunner
A1 Carlos Abud-Mendoza
A1 Diego O Viola
A1 Inmaculada Calvo Penades
A1 Deborah Levy
A1 Jordi Anton
A1 Julia E Calderon
A1 Vyacheslav G Chasnyk
A1 Manuel A Ferrandiz
A1 Vladimir Keltsev
A1 Maria E Paz Gastanaga
A1 Michael Shishov
A1 Alina Lucica Boteanu
A1 Michael Henrickson
A1 Damon Bass
A1 Kenneth Clark
A1 Anne Hammer
A1 Beulah N Ji
A1 Antonio Nino
A1 David A Roth
A1 Herbert Struemper
A1 Mei-Lun Wang
A1 Alberto Martini
A1 Daniel Lovell
A1 Nicolino Ruperto
A1 ,
YR 2020
UL http://ard.bmj.com/content/79/10/1340.abstract
AB Objectives This 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).Methods Patients (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.Results Ninety-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.Conclusion The 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 number NCT01649765.