Belimumab for the treatment of pediatric patients with lupus nephritis

ABSTRACT

Introduction

The FDA approved the anti-BAFF monoclonal antibody, belimumab, in 2011 for adult systemic lupus erythematosus (SLE), in 2019 for pediatric SLE, in 2020 for adult lupus nephritis (LN), and in 2022 for pediatric LN.

Areas covered

We performed a PUBMED database search through November 2022, using ‘belimumab and lupus nephritis,’ ‘belimumab and childhood systemic lupus erythematosus,’ ‘belimumab and pediatric systemic lupus erythematosus,’ and ‘belimumab and juvenile systemic lupus erythematosus’ as the search phrases. We also vetted pertinent references cited in the papers gleaned from the above search, and we drew from our personal literature collections.

Expert opinion

Based on clinical-trials and real-world experience, belimumab is useful and safe in adult SLE and LN. In contrast and despite FDA approval, evidence of effectiveness in pediatric SLE and pediatric LN is very limited. Whereas there was a trend favoring belimumab in the only randomized, controlled trial to date in pediatric SLE, the difference between the belimumab and placebo groups failed to achieve statistical significance. Moreover, there have been no randomized, controlled trials for belimumab in pediatric LN. Based largely on information gleaned from experience in adults, the clinician can cautiously prescribe belimumab to his/her pediatric LN patient and hope for benefit.

KEYWORDS:

• phase-III trials
• real-world experience
• BAFF
• adult SLE
• pediatric SLE

Article highlights

• Belimumab, a monoclonal antibody that neutralizes the B cell survival factor BAFF, is approved for treatment of adult and pediatric SLE and adult and pediatric lupus nephritis (LN).

• The vast majority of the evidence supporting a therapeutic role for belimumab comes from clinical trials and real-world experience in adult SLE.

• Belimumab has an established track record of safety and significant, albeit modest, efficacy, and effectiveness in adult SLE.

• The single randomized, controlled clinical trial of belimumab in pediatric SLE confirmed its safety in children and showed a trend toward efficacy, although this degree of efficacy did not achieve statistical significance.

• In LN, a single randomized, controlled clinical trial of belimumab in adults documented benefit, whereas no such trials have been reported to date in children.

• The fact that extensive real-world experience with multiple immunosuppressive agents (e.g. cyclophosphamide, mycophenolate mofetil) are equally effective (and equally toxic) in adult and pediatric SLE and LN raises realistic hope for similar effectiveness (and similar paucity of toxicity) for belimumab in adult and pediatric SLE and LN.

• Randomized clinical trials in pediatric SLE and pediatric LN are needed to move from ‘hoping’ for a salutary role for belimumab to actually ‘proving’ a salutary role for belimumab in pediatric SLE and pediatric LN.

Declaration of interest

W Stohl has been a site principal investigator for now-completed industry-sponsored multi-center clinical trials of belimumab in adult SLE. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded in part by the Selena Gomez Fund, the USC Thomas D Beardmore, MD, Memorial Endowment Fund, and by a gift from Sandra Kanengiser in memory of her uncle, Jack Norberg, and in honor of Dr Orrin Troum.