Childhood-onset Lupus Nephritis Initial Glucocorticoid-dose Harmonization Trial (LIGHT Trial)

Condition(s) studied

Investigational drug(s) / intervention(s)

High-dose prednisone: All participants will receive two courses of intravenous methylprednisolone pulse therapy (10-30 mg/kg/day for 3 consecutive days per course; maximum 500 mg/day). Participants will then be randomized in a 1:1 ratio to the two treatment groups. In the standard-dose (control) group, oral prednisone will be initiated at 1.4-1.6 mg/kg/day (maximum 60 mg/day), followed by gradual tapering according to the predefined schedule. For participants weighing \<40 kg, doses will be adjusted in proportion to body weight using the following formula: Individual dose = standard dose × body weight (kg) × 0.025. All participants will receive background therapy with oral hydroxychloroquine, mycophenolate mofetil, and intravenous belimumab at standard doses.

Low-dose prednisone: All participants will receive two courses of intravenous methylprednisolone pulse therapy (10-30 mg/kg/day for 3 consecutive days per course; maximum 500 mg/day). Participants will then be randomized in a 1:1 ratio to the two treatment groups. Participants in the intervention group will receive oral prednisone at an initial dose of 0.6-0.8 mg/kg/day, with a maximum dose of 30 mg/day, followed by gradual tapering according to the predefined schedule. For participants weighing \<40 kg, doses will be adjusted in proportion to body weight using the following formula: Individual dose = standard dose × body weight (kg) × 0.025. The estimated cumulative prednisone dose over 24 weeks will be approximately 50% of that in the control group. All participants will receive background therapy with oral hydroxychloroquine, mycophenolate mofetil, and intravenous belimumab at standard doses.

Study summary

Childhood-onset systemic lupus erythematosus (cSLE) is a severe chronic autoimmune disease with a high burden of major-organ involvement. Lupus nephritis (LN) affects more than half of children with SLE, and proliferative LN-including class III, IV, III+V, and IV+V disease-is associated with acute kidney injury, progression to end-stage kidney disease, and poor long-term outcomes.

Glucocorticoids remain a cornerstone of induction therapy for proliferative LN. However, the optimal initial dose in children is uncertain. Although recent adult SLE and LN guidelines increasingly recommend lower-dose glucocorticoid regimens with rapid tapering, pediatric guidelines still commonly recommend high initial prednisone doses of 1.5-2.0 mg/kg/day. Adult trials and comparative observational studies suggest that lower-dose glucocorticoid regimens may preserve efficacy while reducing treatment-related toxicity.

Because cumulative glucocorticoid exposure in children may impair growth, development, psychosocial well-being, and medication adherence, this trial will compare low-dose versus high-dose initial glucocorticoid regimens for induction treatment of pediatric proliferative LN. The objective is to determine whether a lower-dose regimen is non-inferior in efficacy while reducing glucocorticoid-related adverse effects and improving quality of life.

Eligibility

Primary outcome measure(s)

• Total Renal Response at Week 24 — Week 24
  Total renal response (TRR) is defined as achievement of complete renal response (CRR), primary efficacy renal response (PERR), or partial renal response (PRR). Complete renal response (CRR) is defined as meeting both of the following criteria: 1. Proteinuria \<0.5 g/1.73 m², or 24-hour urinary protein excretion \<300 mg/m², or urine protein-to-creatinine ratio (UPCR) \<0.5 g/g; and 2. Estimated glomerular filtration rate (eGFR) within the normal range, or eGFR ≥85% of baseline, or a normal serum creatinine level with an increase of no more than 25% from baseline. Primary efficacy renal response (PERR) is defined as meeting both of the following criteria: 1. UPCR \<0.7 g/g; and 2. eGFR ≥80% of baseline or eGFR ≥60 mL/min/1.73 m². Partial renal response (PRR) is defined as meeting both of the following criteria: 1. A ≥50% reduction in proteinuria from baseline and UPCR \<3 g/g; and 2. eGFR ≥85% of baseline.

Trial sites (8)

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