Safety and efficacy of intravenous belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial
| Autor: | David M. Roth, Deborah M. Levy, Michael Henrickson, Inmaculada Calvo Penades, Carlos Abud-Mendoza, Michael Shishov, Vyacheslav Chasnyk, Julia E Calderon, Antonio Nino, Diego O Viola, Alina Boteanu, Manuel A. Ferrandiz, Maria Gastanaga, Herbert Struemper, Mei-Lun Wang, Anne E. Hammer, Kenneth L. Clark, Hermine I. Brunner, Beulah Ji, Vladimir Keltsev, Nicolino Ruperto, Daniel J. Lovell, Jordi Anton, Damon Bass, Alberto Martini |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Adolescent Immunology Placebo-controlled study DMARDs (biologic) Placebo Antibodies Monoclonal Humanized Systemic Lupus Erythematosus General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Rheumatology Pharmacokinetics Double-Blind Method Internal medicine B-Cell Activating Factor Clinical endpoint Immunology and Allergy Medicine Humans Lupus Erythematosus Systemic 030212 general & internal medicine Adverse effect Child 030203 arthritis & rheumatology Response rate (survey) treatment business.industry Belimumab Treatment Outcome Child Preschool Administration Intravenous Female business Immunosuppressive Agents medicine.drug |
| Zdroj: | Annals of the Rheumatic Diseases |
| ISSN: | 1468-2060 0003-4967 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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