TY - JOUR
T1 - Safety and efficacy of intravenous belimumab in children with systemic lupus erythematosus
T2 - results from a randomised, placebo-controlled trial
AU - Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG)
AU - Brunner, Hermine I
AU - Abud-Mendoza, Carlos
AU - Viola, Diego O
AU - Calvo Penades, Inmaculada
AU - Levy, Deborah
AU - Anton, Jordi
AU - Calderon, Julia E
AU - Chasnyk, Vyacheslav G
AU - Ferrandiz, Manuel A
AU - Keltsev, Vladimir
AU - Paz Gastanaga, Maria E
AU - Shishov, Michael
AU - Boteanu, Alina Lucica
AU - Henrickson, Michael
AU - Bass, Damon
AU - Clark, Kenneth
AU - Hammer, Anne
AU - Ji, Beulah N
AU - Nino, Antonio
AU - Roth, David A
AU - Struemper, Herbert
AU - Wang, Mei-Lun
AU - Martini, Alberto
AU - Lovell, Daniel
AU - Ruperto, Nicolino
N1 - © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.
PY - 2020/10
Y1 - 2020/10
N2 - 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.
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.
KW - Administration, Intravenous
KW - Adolescent
KW - Antibodies, Monoclonal, Humanized/therapeutic use
KW - B-Cell Activating Factor/antagonists & inhibitors
KW - Child
KW - Child, Preschool
KW - Double-Blind Method
KW - Female
KW - Humans
KW - Immunosuppressive Agents/therapeutic use
KW - Lupus Erythematosus, Systemic/drug therapy
KW - Male
KW - Treatment Outcome
U2 - 10.1136/annrheumdis-2020-217101
DO - 10.1136/annrheumdis-2020-217101
M3 - Article
C2 - 32699034
VL - 79
SP - 1340
EP - 1348
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
SN - 0003-4967
IS - 10
ER -