ACR 2016. Abstract 5L. Speed of Remission with the Use of Voclosporin, MMF & Low Dose Steroids: Results of a Global Lupus Nephritis Study
Mary Anne Dooley et al.
Results: The groups were generally well-balanced for age, gender and race, with a trend to higher proteinuria and lower eGFR data in the low dose VCS arm. The trial met its primary endpoint with superior CR rates in the low dose arm (OR: 2.03, p=0.045). There was a statistically significant improvement in time to CR and time to PR in both treatment arms (P<.01). A mean reduction in serum creatinine was seen in both arms (0.2 mg/dL low, 0.1 high; p<.001). BP did not vary by group. Over 90% of subjects experienced at least one adverse event; the most common being infectious (56.2% low, 63.6% high and 50.0% control), GI disorders (41.6% low, 52.3% high and 36.4% control). More serious adverse events occurred in the voclosporin groups (25.8% low, 25.0% high, 15.8% control), and were consistent with those observed in LN patients. Most deaths occurred in the first 2 months and were: low dose (infection-3, ARDS-2, thrombotic-3, cardiac tamponade, pulmonary hemorrhage), high dose (infection, PE) and control (CVA). All were considered unrelated to drug exposure by the investigators.
Conclusion: The AURA study is the first global LN study to meet its primary end-point, Response rate was rapid; increasing CR in the VCS arms was seen by week 6. This study demonstrated the positive additive effects of VCS, despite the rigorous steroid taper (mean steroid dose 4 mg at Week 16). Adverse events were higher in the VCS treatment arms, consistent with increased immunosuppression. The overall mortality rate was similar to other recent LN trials (ALMS 3.8%, ALLURE 4.7%, BELONG 3.7%), with a higher mortality rate in the low dose group. These promising data will be used to plan subsequent studies of voclosporin in LN.
CARE Faculty Perspective: This study indicates that there may soon be a new therapy option available to treat active renal lupus. Where this novel calcineurin inhibitor, voclosporin, will fit in with SLE treatment in the clinic is currently unknown. Combination immune suppressives in SLE nephritis may have added benefits compared
In another recent published lupus nephritis study (2015) with tacrilomus with mycophenylate mofetil, there was superiority to cyclophosphamide mono therapy.* Our treatment paradigm in renal lupus is likely to markedly change in the new future.
* Liu Z. Ann Intern Med 2015:162:18-26