Induction therapy and outcome of proliferative lupus nephritis in the top end of Northern Australia - a single centre study retrospective study.

BACKGROUND

Lupus nephritis is a common manifestation of Systemic Lupus Erythematosus. Mycophenolate is recommended by guidelines for induction therapy in patients with proliferative lupus nephritis and nephrotic range proteinuria Class V lupus nephritis. Indigenous Australians suffer disproportionally from systemic lupus erythematosus compared to non-Indigenous Australians (Anstey et al., Aust N Z J Med 23:646-651, 1993; Segasothy et al., Lupus 10:439-444, 2001; Bossingham, Lupus 12:327-331, 2003; Grennan et al., Aust N Z J Med 25:182-183, 1995).

METHODS

We retrospectively identified patients with newly diagnosed biopsy-proven class III lupus nephritis, class IV lupus nephritis and class V lupus nephritis with nephrotic range proteinuria from 1 Jan 2010 to 31 Dec 2019 in our institution and examined for the patterns of prescribed induction therapy and clinical outcome. The primary efficacy outcome of interest was the incidence of complete response (CR) and partial response (PR) at one-year post diagnosis as defined by the Kidney Disease: Improving Global Outcome (KDIGO) guideline. Secondary efficacy outcome was a composite of renal adverse outcome in the follow-up period. Adverse effect outcome of interest was any hospitalisations secondary to infections in the follow-up period. Continuous variables were compared using Student's t-test or Mann-Whitney U-test. Categorical variables were summarised using frequencies and percentages and assessed by Fisher's exact test. Time-to-event data was compared using the Kaplan-Meier method and Log-rank test. Count data were assessed using the Poisson's regression method and expressed as incident rate ratio.

RESULTS

Twenty of the 23 patients included in the analysis were managed with mycophenolate induction upfront. Indigenous Australian patients (N = 15), compared to non-Indigenous patients (N = 5) received lower cumulative dose of mycophenolate mofetil over the 24 weeks (375 g vs. 256 g, p < 0.05), had a non-significant lower incidence of complete remission at 12 months (60% vs. 40%, p = 0.617), higher incidence of composite renal adverse outcome (0/5 patients vs. 5/15 patients, p = 0.20) and higher incidence of infection related hospitalisations, (incident rate ratio 3.66, 95% confidence interval 0.89-15.09, p = 0.073).

CONCLUSION

Mycophenolate as upfront induction in Indigenous Australian patients were associated with lower incidence of remission and higher incidence of adverse outcomes. These observations bring the safety and efficacy profile of mycophenolate in Indigenous Australians into question.