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.
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