Risks, Benefits of IV Belimumab in Children With SLE Consistent With Adults

By Marilynn Larkin

August 07, 2020

NEW YORK (Reuters Health) - Intravenous belimumab 10 mg/kg every four weeks was safe and effective in childhood-onset systemic lupus erythematosus (cSLE) in a phase-2 placebo-controlled trial.

As reported in the Annals of Rheumatic Diseases, Dr. Hermine Brunner of Cincinnati Children's Hospital Medical Center in Ohio randomized 93 young people (median age 14.5; about 45% female) to 10 mg/kg IV belimumab or placebo every four weeks, plus standard SLE therapy.

At week 52, there were more SLE Responder Index (SRI4) responders with belimumab versus placebo (52.8% vs 43.6%; odds ratio, 1.49). More belimumab patients also achieved Pediatric Rheumatology International Trials Organization/American College of Rheumatology responses using alternative definitions of 30 (52.8% vs. 27.5%; OR 2.92) and 50 (60.4% vs. 35%; OR 2.74), as well as sustained responses for SRI4 (43.4% vs. 41%; OR 1.08) and parent-global positive responses (59.1% vs. 33.3%; OR 3.49).

The rate of severe adverse events was 17% with belimumab versus 35% with placebo; there was one death in the placebo group.

At week 52, the geometric mean belimumab trough concentration was 56.2 mcg/mL.

The authors conclude, "The belimumab intravenous pharmacokinetics and benefit-risk profile in cSLE are consistent with adult belimumab studies and the 10 mg/kg every four weeks dose is appropriate."

Dr. Lisa Imundo, Associate Professor of Pediatrics and Director of Adolescent Rheumatology at Columbia University Irving Medical Center in New York City called the study "very important," noting that it is "developing a template of how to do studies in children with lupus."

"We are navigating how to make this process easier to achieve approval for other promising therapies going forward," Dr. Imundo, who was not involved in the study.

"We now understand that childhood- and adult-onset SLE are the same disease," she told Reuters Health by email. "The FDA has indicated that future studies can be streamlined to enroll both adults and teenagers in the same study with a goal of getting medications approved more quickly for pediatric-onset diseases."

"We know that childhood-onset lupus patients have a higher risk of developing renal lupus," she noted "We will be looking more closely at patients who continue to take belimumab to see if they have fewer flairs and less severe renal disease than patients who do not take it. This is not proven yet, but there is an indication we might be able to modulate the disease course in patients at risk with this type of medication."

"For younger children, IV infusions will be a best administration formulation," she added. "However, for teenagers, a subcutaneous form is now available that will make this even more accessible as a maintenance option for cSLE patients."

Dr. Anne Eberhard, Professor of Pediatrics and Dr. Joyce Hui, Assistant Professor of Pediatrics, both of Hofstra-Northwell School of Medicine in Lake Success, New York, also commented in an email to Reuters Health. "Although giving IV belimumab means patients must take time out of school and/or work to receive the medication, it also ensures that the patient is actually compliant with his/her treatment, which is a big concern in adolescents with cSLE," they said.

The study's evaluation of outcomes at weeks 44-52, they note, "would be consistent with our real-world experience of belimumab that it can take over six months to observe improvement in disease activity and that the response may not be sustained."

"Belimumab has also been used as a steroid-sparing agent in cSLE; often being added to a patient's medication regimen in the hopes that one can lower his/her corticosteroid dose," they continued. "Our and others' experience has shown that the addition of belimumab can result in a reduction of daily corticosteroid dose in some, but not, all cSLE patients."

"The trial certainly provides ample evidence supporting FDA approval; however, we await the results from (the group's) longer term studies that are currently underway, to determine the precise role of Belimumab in the treatment of cSLE," they conclude.

Dr. Brunner did not respond to requests for a comment.

The study was funded by GSK. Seven authors are employees of the company, one is a former employee and Dr. Brunner and many others have received funds from the company.

SOURCE: https://bit.ly/2C4ZduR Annals of Rheumatic Diseases, online July 22, 2020.