Outcome of lupus nephritis patients treated with an anti‐CD40 monoclonal antibody according to kidney biopsy features

Objective A phase II trial tested different doses of the anti‐CD40 monoclonal antibody BI655064 as add‐on therapy to the standard of care in class III or IV Lupus Nephritis (LN) patients with active disease. A post‐hoc analysis showed a potential benefit of the higher tested doses (180mg/240mg) versus low dose (120mg)/placebo. We investigated whether the treatment effect of BI655064 on kidney outcomes may be modified by the presence of glomerular monocytes, a target for this drug with a well‐known role in LN pathogenesis. Methods 101 renal biopsies of LN patients enrolled in the BI655064 trial were scored centrally. eGFR and spot urine protein/urine creatinine ratio (UP/UC) and Complete Renal Response (CRR) were evaluated over 52 weeks. Patients were divided according to a “Better” or “Worse” performance than the average of all patients in the cohort, predicted by a mixed model for repeated measurements. Logistic regression models adjusted for potential confounders assessed the association between different treatment doses and outcomes according to the presence or absence of monocytes. Results A higher BI655064 dose (180/240mg) was associated with better outcomes of UP/UC and CRR when glomerular monocytes were present in kidney biopsies (OR 3.66[1.09‐12.3], P=0.04; OR 4.58[1.24‐16.9], P=0.02). A trend toward improved eGFR was also observed in these patients (P 52‐weeks=0.08). Conclusions In LN kidney biopsies with glomerular monocytes, high‐dose BI655064 treatment improved proteinuria at 52 weeks and resulted in a higher CRR compared to biopsies without glomerular monocytes. Histologic features may guide the choice of treatment for individual LN patients.