Belimumab Promising for Children with Lupus Nephritis

In late July, the U.S. Food & Drug Administration (FDA) approved belimumab (Benlysta) for the treatment of children aged 5–17 years old with active lupus nephritis who are receiving standard therapy.¹ Despite recent advances in treatment options for patients with systemic lupus erythematosus (SLE), those with kidney involvement face the possibility of developing end-stage renal disease and needing subsequent hemodialysis or transplantation. Belimumab may improve the prognosis for pediatric patients with lupus.

The indications for the intravenous (IV) formulation of belimumab have been expanded to include pediatric patients with SLE, as well as those with active lupus nephritis.² The recommended dosing of IV belimumab for pediatric patients is 10 mg/kg every two weeks for the first three doses, with subsequent infusions given at four-week intervals.³

Background

The efficacy and safety of belimumab were evaluated for one year in a randomized, double-blind, placebo-controlled study (N=93; NCT01649765).⁴ Similar to the clinical trials of belimumab in adults, enrolled pediatric patients had to have a clinical diagnosis of SLE according to the ACR classification criteria, active SLE (i.e., defined as a SELENA-SLEDAI score of at least 6) and the presence of autoantibodies at screening.

The researchers enrolled 93 pediatric patients aged 5 to 17 years who were on stable treatment regimens for their SLE (i.e., standard therapy) and had similar inclusion and exclusion criteria as participants in the clinical trials for adults. The standard therapy included corticosteroids, antimalarials, non-steroidal anti-inflammatory drugs (NSAIDs) and/or immunosuppressives, alone or in combination. Use of other biologics and IV cyclophosphamide was not allowed during the course of this study.

The median patient age was 15 years (range: 6–17 years), and most patients were female (95%). At baseline, more than half of the patients had active involvement of at least three organ systems, the most common of which were the mucocutaneous (91%), immunologic (74%) and musculoskeletal (73%). Nineteen percent of patients had some degree of kidney disease, with less than 7% of patients having their cardio-respiratory, hematologic, central nervous system or vascular systems affected. The study’s primary efficacy end point was the SLE Responder Index (SRI-4) at week 52, as described in the adult trials of IV belimumab.

Results

Forty patients received placebo and standard therapy, and 53 patients received belimumab plus standard therapy. A higher proportion of patients receiving belimumab plus standard therapy achieved an SRI-4 response than patients who received placebo plus standard therapy (44% vs. 53%, odds ratio [OR]=1.49 (0.64, 3.46)).

At baseline, 95% of patients were receiving prednisone. Of the patients treated with belimumab plus standard therapy, no difference was found in the frequency of prednisone reduction between the belimumab- and placebo-treated groups (20.0% and 21%, respectively). This study was not designed or powered to assess a steroid-sparing effect.

The probability of having an SLE disease flare was measured by the modified SELENA-SLEDAI Flare Index. The proportion of patients reporting at least one severe flare during the study was lower in patients treated with belimumab plus standard therapy (17%) than in the proportion of patients treated with placebo plus standard therapy (35%). The addition of belimumab to standard therapies resulted in a 64% lower risk of experiencing a severe disease flare during the study than patients who received placebo plus standard therapy.

Of the patients who had a severe flare, the median time to the first severe flare was 150 days in patients receiving belimumab plus standard therapy and 113 days in patients receiving placebo plus standard therapy. In the 53 patients who received belimumab, no formation of anti-belimumab antibodies occurred.

In this patient population, belimumab’s pharmacokinetics were consistent with those of the adult population with SLE. No new safety signals were identified. This FDA approval marks a significant step forward, providing treatment options for pediatric patients at risk of developing early renal damage and failure due to SLE.

References

1. BLA supplement approval: Benlysta for pediatric patients. U.S. Food & Drug Administration. 2022 Jul 27.
2. News release: GSK announces U.S. FDA approval of Benlysta (belimumab) for pediatric patients with active lupus nephritis. 2022 Jul 27.
3. Highlights and prescribing information. Benlysta.  U.S. Food & Drug Administration. 2022 Jul 27.
4. Pediatric Lupus Trial of Belimumab Plus Background Standard Therapy (PLUTO; NCT01649765). ClinicalTrials.gov.