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

abstract

  • 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%27 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%25 vs 43.6%25; OR 1.49 (95%25 CI 0.64 to 3.46)). PRINTO/ACR 30 alternative (52.8%25 vs 27.5%25; OR 2.92 (95%25 CI 1.19 to 7.17)) and PRINTO/ACR 50 (60.4%25 vs 35.0%25; OR 2.74 (95%25 CI 1.15 to 6.54)) responses were more frequent with belimumab than placebo, as were sustained responses for SRI4 (belimumab, 43.4%25; placebo, 41.0%25; OR 1.08 (95%25 CI 0.46 to 2.52)) and Parent-global (belimumab, 59.1%25; placebo, 33.3%25; OR 3.49 (95%25 CI 1.23 to 9.91)). Serious adverse events were reported in 17.0%25 of belimumab patients and 35.0%25 of placebo patients; one death occurred (placebo). Week-52, geometric mean (95%25 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. ©
  • 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%25 vs 43.6%25; OR 1.49 (95%25 CI 0.64 to 3.46)). PRINTO/ACR 30 alternative (52.8%25 vs 27.5%25; OR 2.92 (95%25 CI 1.19 to 7.17)) and PRINTO/ACR 50 (60.4%25 vs 35.0%25; OR 2.74 (95%25 CI 1.15 to 6.54)) responses were more frequent with belimumab than placebo, as were sustained responses for SRI4 (belimumab, 43.4%25; placebo, 41.0%25; OR 1.08 (95%25 CI 0.46 to 2.52)) and Parent-global (belimumab, 59.1%25; placebo, 33.3%25; OR 3.49 (95%25 CI 1.23 to 9.91)). Serious adverse events were reported in 17.0%25 of belimumab patients and 35.0%25 of placebo patients; one death occurred (placebo). Week-52, geometric mean (95%25 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. ©

publication date

  • 2020-01-01