Efficacy and Safety of Intravenous Belimumab in Children with Systemic Lupus Erythematosus

Hermine I. Brunner¹, Carlos Abud-Mendoza², Diego I. Viola³, Inmaculada Calvo⁴, Deborah M. Levy⁵, Julia Calderon Gallegos⁶, Manuel Ferrandiz⁷, Vyacheslav Chasnyk⁸, Vladmir Keltsev⁹, Jordi Anton¹⁰, Maria Paz¹¹, Michael Shishov¹², Alina Lucica Boteanu¹³, Michael Henrickson¹⁴, Damon Bass¹⁵, Kenneth Clark¹⁶, Anne Hammer¹⁵, Beulah Ji¹⁶, David Roth¹⁵, Herbert Struemper¹⁷, Mei-Lun Wang¹⁸, Alberto Martini¹⁹, Daniel J Lovell²⁰ and Nicola Ruperto¹⁹, ¹Pediatric Rheumatology Collaborative Study Group (PRCSG), Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, ²Hospital Central Dr. Ignacio Morones Prieto, San Luis Potosy, Mexico, ³CAICI Institute, Rosario City, Santa Fe State, Argentina, ⁴Hospital Universitario La Fe, Valencia, Spain, ⁵Rheumatology, Hospital for Sick Children, Toronto, ON, Canada, ⁶Instituto de Ginecologia y Reproduccion, Santiago De Surco, Peru, ⁷Instituto Nacional de Salud del Nino, Lima, Peru, ⁸St Petersburg State Pediatric Medical Academy, St Petersburg, Russian Federation, ⁹City Clinical Hospital No.5, Tolyatti, Russian Federation, ¹⁰SJD Barcelona Children’s Hospital, Barcelona, Spain, ¹¹Clinica Anglo Americana, Lima, Peru, ¹²Phoenix Children's Hospital, Phoenix, AZ, ¹³University Hospital Ramón y Cajal, Madrid, Spain, ¹⁴Cincinnati Children’s Medical Center, Cincinnati, OH, ¹⁵GlaxoSmithKline, Philadelphia, PA, ¹⁶GlaxoSmithKline, Stevenage, United Kingdom, ¹⁷GlaxoSmithKline, Research Triangle Park, NC, ¹⁸GlaxoSmithKline, Collegeville, PA, ¹⁹Universita di Genova Pediatria II, Genova, Italy, ²⁰Cincinnati Children's Medical Center, Cincinnati, OH

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: belimumab, juvenile SLE, Pediatric rheumatology and systemic lupus erythematosus (SLE)

Session Information

Date: Tuesday, October 23, 2018

Title: 5T107 ACR Abstract: Pediatric Rheum–Clinical II: Treatment Update (2862–2867)

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

<>Background/Purpose: Belimumab (BEL) is approved in adults with active systemic lupus erythematosus (SLE). There are no approved biologic therapies for pediatric patients with childhood-onset SLE (cSLE). This Phase 2, multicenter, randomized, double-blind trial (NCT01649765) evaluated the efficacy, safety, and pharmacokinetics (PK) of intravenous (IV) BEL vs placebo (PBO), plus standard therapy (SoC), in cSLE. <>Methods: Patients with cSLE aged 5–17 years were randomized to BEL 10 mg/kg IV or PBO every 4 weeks, plus SoC. The primary endpoint was SLE Responder Index 4 (SRI4) at Week (Wk) 52. Major secondary endpoints were: proportion of patients achieving the Pediatric Rheumatology International Trials Organization/ACR (PRINTO/ACR) cSLE Evaluation criteria for improvement using two definitions at Wk 52; cSLE core response variables at Wk 52 (Table); and sustained SRI4 and Parent Global Assessment (ParentGA) responses (Wks 44–52). Other secondary endpoints included time to first severe flare (modified SELENA-SLEDAI Flare Index). Safety and PK were assessed. The study was not powered for statistical testing.

Results: 93 patients comprised the intent-to-treat population (BEL, 53; PBO, 40). Mean (SD) baseline SELENA-SLEDAI was 10.4 (3.63) for PBO and 10.3 (3.34) for BEL; 17 (42.5%) PBO and 22 (41.5%) BEL patients were anti-dsDNA positive and had low complement. At Wk 52 there were numerically more SRI4 and PRINTO/ACR responders in BEL vs PBO (Figure). Numerically more BEL patients had sustained SRI4 and ParentGA responses at Wks 44–52 vs PBO (Figure). Changes in cSLE core response variables are shown in the Table. Severe flares were 62% less frequent with BEL vs PBO (hazard ratio 0.38 [95% CI 0.18, 0.82]); median (IQR) time to first severe flare was 159.5 (47.5, 314.5) vs 82.0 (57.0, 228.0) days for BEL vs PBO. Overall incidence of adverse events (AEs) was similar between groups. 9/53 (17%) BEL patients experienced ≥1 SAE vs 14/40 (35%) PBO patients. 1/53 [1.9%] BEL patients experienced depression/suicide/self-injury vs 4/40 [10%] PBO patients. One PBO patient died of acute pancreatitis. At Wk 52 the geometric mean (95% CI) BEL trough concentration was 44.96 (27.52, 73.43) µg/mL for patients aged 5–11 years, and 59.71 (46.41, 76.81) µg/mL for patients aged 12–17 years.

Conclusion: The benefit/risk profile and PK of BEL IV plus SoC in cSLE are generally consistent with those in adult BEL study populations. The 10 mg/kg IV dose used in adults may be an appropriate dose in cSLE.

Disclosure: H. I. Brunner, GlaxoSmithKline (GSK), F. Hoffman-La Roche, Novartis, Pfizer, Sanofi Aventis, Merck Serono, 5,AbbVie, Amgen, Biogenidec, Alter, AstraZeneca, Baxalta Biosimilars, Biogenidec, Boehringer, BMS, Celgene, CrescendoBio, EMD Serono, F. Hoffman-La Roche, Janssen, MedImmune, Novartis, Pfizer, Sanofi Aventis, Takeda, and UCB Biosciences GmbH, 5; C. Abud-Mendoza, None; D. I. Viola, None; I. Calvo, None; D. M. Levy, None; J. Calderon Gallegos, None; M. Ferrandiz, None; V. Chasnyk, None; V. Keltsev, None; J. Anton, None; M. Paz, None; M. Shishov, None; A. L. Boteanu, None; M. Henrickson, None; D. Bass, GSK, 1, 3; K. Clark, GSK, 1, 3; A. Hammer, GSK, 1, 3; B. Ji, GSK, 1, 3; D. Roth, GSK, 1, 3; H. Struemper, GSK, 1, 3; M. L. Wang, GSK, 1, 3; A. Martini, Abbvie, Biogen, Boehringer, Bristol Myers and Squibb, EMD Serono, Janssen, Novartis, Pfizer, R-Pharm on behalf of the Gaslini Institute, 5; D. J. Lovell, AstraZeneca, Amgen, Abbott, Pfizer, 5,Wyeth Pharma, 8; N. Ruperto, Abbott, AbbVie, Amgen, Biogenidec, Astellas, Alter, AstraZeneca, Baxalta Biosimilars, Boehringer, BMS, CD-Pharma,Celgene, CrescendoBio, EMD Serono, Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Rewind Arms, 5, 6, 7, 8,R-Pharma, Sanofi Aventis, Servier, Sinergie, Takeda, Vertex, UCB Biosciences GmbH., 5, 6, 7, 8,BMS, "Francesco Angelini", GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma, Wyeth., 2.

To cite this abstract in AMA style:

Brunner HI, Abud-Mendoza C, Viola DI, Calvo I, Levy DM, Calderon Gallegos J, Ferrandiz M, Chasnyk V, Keltsev V, Anton J, Paz M, Shishov M, Boteanu AL, Henrickson M, Bass D, Clark K, Hammer A, Ji B, Roth D, Struemper H, Wang ML, Martini A, Lovell DJ, Ruperto N. Efficacy and Safety of Intravenous Belimumab in Children with Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/efficacy-and-safety-of-intravenous-belimumab-in-children-with-systemic-lupus-erythematosus/. Accessed .

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