Voclosporin in a Complex Lupus Nephritis Population: Real-Life Outcomes Beyond Clinical Trials

Background: Voclosporin is a novel calcineurin inhibitor approved for the treatment of lupus nephritis (LN). We present our initial experience using voclosporin in patients with LN in a nephrology practice setting. Methods: We retrospectively reviewed clinical data from six patients who initiated voclosporin between March and September 2024. Baseline characteristics, comorbidities, indication for voclosporin, concomitant immunosuppressants, adverse events, and evolution of clinical and laboratory parameters were analyzed Results: Three patients started voclosporin due to tremor caused by other calcineurin inhibitors, one due to intolerance to other agents, one due to uncontrolled proteinuria, and one due to variable tacrolimus levels. Four had mixed class (III/IV+V) LN, one had class V, and one had class IV LN. Two patients had refractory LN despite ≥5 previous immunosuppressive regimens. Median treatment duration was 13 weeks (range 2–17). Initial prednisone dose was ≤5 mg in five of six patients. Two patients discontinued voclosporin: one due to gingival hypertrophy, the other due to nausea. Among the four patients completing ≥12 weeks of treatment, proteinuria decreased from a median of 2.08 g/g (range 1.22–5.4) to 0.21 g/g (0.16–3.3). Complement C3 levels improved in three patients. SLEDAI score dropped to 0 in three of four patients with complete data. No serious voclosporin-related adverse events were reported Conclusion: In our cohort, voclosporin was used in patients with refractory LN or prior treatment-related adverse effects, enabling steroid minimization and clinical and serologic improvement. Although limited by small sample size, we observed favorable responses in most patients completing ≥3 months of therapy. Table 1. Baseline Clinical Characteristics and Voclosporin Treatment Details - Voclosporin start date InitialSLDAI Biopsy class Reason for initiation Other immunosuppression at the end of follow-up Secondary effects Initial prednisone dose Duration of treatment(months) 1 10/04/2024 8 V Tremor MethotrexatePS 6 mg NO 25 mg 13 2 25/04/24 12 IV Intolerance to other CNIs AnifrolumabPS 2.5 mg NO 5 mg 13 3 21/03/24 18 III+V Tremor AnifrolumabMMFPS 5 mg NO Bolus 250 mg 15 4 07/03/24(partial remission) 6 IV+V Tremor, alopecia MMF NO 0 17 5 01/08/24 6 IV+V No control of proteinuria HSCT, CNIs Gingival hypertrophy (stop treatment) 2.5 mg 7 6 19/09/24 6 V Fluctuating tacrolimus levels PS 2.5 mg, CNIs, MMF, belimumab Nausea (stop treatment) 5 mg 2 Abbreviations: PS (prednisone), CNIs (Calcineurin Inhibitors), MMF (Mycophenolate mofetil), HSCT (Autologous hematopoietic stem cell transplantation)