Long-term outcomes with rituximab as add-on therapy in severe childhood-onset lupus nephritis

Background Long-term data pertaining to rituximab as add-on therapy in childhood-onset lupus nephritis (cLN) is scarce. Methods A retrospective cohort study was conducted on all patients with proliferative cLN, diagnosed <= 18 years and between 2005 and 2021, who received rituximab for LN episodes that were life/organ threatening and/or treatment resistant to standard immunosuppression. Results Fourteen patients with cLN (female, n = 10) were included, with median follow-up period of 6.9 years. LN episodes (class III, n = 1; class IV, n = 11; class IV + V, n = 2) requiring rituximab occurred at 15.6 years (IQR 12.8-17.3), urine protein:creatinine ratio was 8.2 mg/mg (IQR 3.4-10.1) and eGFR was 28 mL/min/1.73 m(2) (IQR 24-69) prior to rituximab treatment. Ten and four patients received rituximab at 1500 mg/m(2) and 750 mg/m(2), which were given at 46.5 days (IQR 19-69) after commencement of standard therapies. Treatment with rituximab resulted in improvements in proteinuria (ps < 0.001), eGFR (ps < 0.01) and serological parameters, including haemoglobin levels, complement 3 levels and anti-dsDNA antibodies, compared with baseline. Rates of complete/partial remission at 6-, 12-and 24-month post-rituximab were 28.6/42.8%, 64.2/21.4% and 69.2/15.3%. All three patients who required acute kidney replacement therapy became dialysis-free after rituximab. Relapse rate following rituximab was 0.11 episodes/patient-year. There was no lethal complication or severe infusion reaction. Hypogammaglobulinaemia was the most frequent complication (45%) but was mostly asymptomatic. Neutropenia and infections were observed in 20% and 25% of treatments. Upon last follow-up, three (21%) and two (14%) patients developed chronic kidney disease (stage 2, n = 2; stage 4; n = 1) and kidney failure, respectively. Conclusion Add-on rituximab is an effective and safe rescue therapy for cLN patients with life-/organ-threatening manifestations or treatment-resistance.