Long-term voclosporin use in lupus nephritis: Results from AURORA 2

At the American College of Rheumatology (ACR) Convergence 2022, Arriens¹ presented results from the phase III AURORA 2 continuation study. The double-blind AURORA studies investigated the use of voclosporin in patients with lupus nephritis (LN) already receiving treatment with mycophenolate mofetil and/or oral steroids, compared with control.¹

LN is a frequent complication in patients with systemic lupus erythematosus and LN episodes are associated with kidney failure.¹ Voclosporin is a calcineurin inhibitor that was approved in 2021 by the U.S. Food and Drug Administration (FDA) for use in adults with active LN.² Results from the phase III AURORA 1 study showed that patients receiving voclosporin had significantly increased complete renal response rates compared with the control group (briefly summarized in our previous article on the management of LN here).¹

Study design¹

In AURORA 1, patients followed a rapid glucocorticoid taper schedule (Figure 1). The final dose of glucocorticoid in AURORA 1 was the starting dose in AURORA 2, which could then be adjusted further by the study investigator. AURORA 2 was a continuation study evaluating 216 patients for an additional 2 years. Both studies were blinded, placebo-controlled studies.

BID, twice daily; IV, intravenous; MMF, mycophenolate mofetil.
*Adapted from Arriens.¹

Results¹

In AURORA 2, patient characteristics at baseline were generally well balanced between arms (Table 1).

Table 1. Baseline patient characteristics in AURORA 2*

eGFR, estimated glomerular filtration rate; LN, lupus nephritis; UPCR, urine protein creatinine ratio. *Adapted from Arriens.1
Characteristic	Control (n = 100)	Voclosporin (n = 116)
Mean age, years	35.4	32.3
Female, %	88.0	90.5
Race, %
White	40.0	37.9
Asian	30.0	25.9
Black	7.0	15.5
Other	23.0	20.7
Mean time since initial LN diagnosis, years	4.8	5.0
Pretreatment corrected eGFR, mL/min/1.73 m2	78.9	79.6
Pretreatment UPCR, mg/mg	3.9	3.9

Safety

The rates of adverse events in both groups decreased over the 3 years, with a higher percentage of renal adverse events in patients treated with voclosporin (Table 2). Estimated glomerular filtration rate reductions and hypertension occurred at a higher rate in Year 1 in voclosporin-treated patients compared with the control group (19% vs 6%, respectively, and 20.7% vs 6%, respectively), but rates of these events decreased over time (at Year 3; 3.9% vs 2.4%, respectively, and 2.9% vs 2.4%, respectively). The mean change in estimated glomerular filtration rate from the baseline of AURORA 2 (Month 12 following the start of AURORA 1) to Month 36 was minimal in both voclosporin and control patients.

Table 2. Overall adverse events during AURORA 1 and 2*

eGFR, estimated glomerular filtration rate. *Adapted from Arriens.1
Adverse event, %	Control	Voclosporin
Adverse event	95.0	92.2
Serious adverse event	28.0	26.7
Treatment-related serious adverse event	4.0	4.3
eGFR decreased	9.0	24.1
Hypertension	13.0	26.7
Renal impairment	2.0	5.2
Acute kidney injury	0	2.6

Efficacy

The reductions in urine protein creatinine ratio (UPCR) seen in AURORA 1 were maintained until the 4-week follow-up following study drug discontinuation of AURORA 2. More patients treated with voclosporin achieved a UPCR ≤0.5 mg/mg compared with the control at all time points (Figure 2).

FUP, follow-up; UPCR, urine protein creatinine ratio.
*Adapted from Arriens.¹

A good renal outcome, defined as an adequate response (sustained reduction in UPCR ≤0.7 mg/mg) without renal flare (an increase in UPCR to >1.0 mg/mg from post-response baseline <0.2 mg/mg or >2 mg/mg from post-response baseline of 0.2–1.0 mg/mg), was achieved by significantly more patients receiving voclosporin (66.4%) compared with control (54%; odds ratio, 0.56; 95% confidence interval, 0.32–0.99; p = 0.045).

Conclusion

The reductions in UPCR seen in patients treated with voclosporin in AURORA 1 were maintained until the end of AURORA 2 and into the follow-up period. A total of 66.4% of patients treated with voclosporin achieved a good renal response, with no new safety signals. In addition, although calcineurin inhibitors, such as voclosporin, can cause kidney injury and thus cause a decrease in eGFR, the initial decrease in eGFR recovered to baseline levels and remained stable through the 3 years in voclosporin-treated patients and following the completion of study drug treatment. Arriens¹ concluded that AURORA 2 demonstrates voclosporin can be used safely long term in combination with mycophenolate mofetil and steroids for patients with LN.