Effectiveness of Belimumab for Glucocorticoid Discontinuation in Juvenile-onset Lupus Nephritis

Introduction

Lupus nephritis (LN) is a major complication occurring in 40% of patients with systemic lupus erythematosus (SLE).¹ Glucocorticoids (GCs) are the cornerstone treatment for SLE. Although GC use in the long term should ideally be discontinued owing to the associated side effects, such as cataracts, psychiatric disorders, osteoporosis, cardiovascular disease, and infection,^2,3 no safe method currently exists. Belimumab is a human monoclonal antibody that binds to a soluble B lymphocyte stimulator to reduce the number of activated B cells and is effective in treating severe LN.¹ We administered belimumab following GC discontinuation in patients with LN.

Case Series

Belimumab was administered to six patients diagnosed with LN Type IV between 2006 and 2016. All patients received nine sets of methylprednisolone pulse therapy (MPT) and mycophenolate mofetil (MMF) as induction therapy. Patients achieved remission and received maintenance therapy for 3–12 years before starting belimumab therapy. Maintenance therapies included prednisolone, MMF, tacrolimus (Tac), and hydroxychloroquine (HCQ). Belimumab was administered during 2017–2019 at a dosage of 10 mg/kg on days 1, 15, and 29, and subsequently once every 4–5 weeks. Prednisolone reduction was initiated after clinical remission; three cases were serologically active clinically quiescent (SACQ). Prednisolone was tapered from an initial dosage of 6–20 mg by 2.5–5 mg every month until reaching a dosage of 5 mg. Subsequently, the dosage was reduced by 1 mg every 6 months. Flares were defined using the SELENA-SLEDAI Flare Index.⁴ One patient was transferred to the adult department during follow-up, and five patients underwent continuous therapy [Table 1]. No cases of severe hypersensitivity reaction, infection, progressive multifocal leukoencephalopathy, interstitial pneumonia, or depression, which are known side effects of belimumab, were observed.

Discussion

In five cases of LN, prednisolone was discontinued after administering belimumab, and no flares occurred 8–38 months after prednisolone discontinuation. Renal function was normal in all patients. Some reports suggest that prednisolone should not be discontinued but maintained at 7.5 mg or less⁵ or 5 mg or less.⁶ However, considering their side effects, GCs should be discontinued as much as possible. Factors that suppress relapse include maintenance of remission for >5 years⁷ and intensive treatment (induction with MPT and maintenance with MMF and/or Tac).⁸ Risk factors for relapse include SACQ,^7,9 history of LN,⁷ and age under 40 years.⁹ In our cases, three patients had SACQ, remission period was <3 years, and the age at prednisolone discontinuation was <27 years. In Cases 1 and 5, the flare could not be suppressed, even with intensive treatment; as side effects of prednisolone were also observed, prednisolone was discontinued despite SACQ. Belimumab resulted in complete remission and long-term prevention of flares. Belimumab should be administered in cases where conventional therapy does not result in sustained remission.

Reports on how to reduce prednisolone include immediate discontinuation from 5 mg, which increases the flare risk by four-fold compared with the maintenance group,¹⁰ and gradual prednisolone discontinuation from 5 mg over 12–24 months, which reduces the flare risk.⁹ In this study, prednisolone was discontinued over 2.5 years; however, the dose could have been reduced at a faster rate.

Conclusion

Belimumab was effective for discontinuing GCs in cases of LN. Further studies with more patients are needed to validate our results.