Tacrolimus did not differ significantly from mycophenolate in lupus nephritis, and serious infections were fewer

Design

Multicentre randomised controlled trial, 96 weeks

Population

130 Asian patients with biopsy-proven class III/IV (± V) lupus nephritis

Primary outcome

Sustained renal response at week 96

Effect

58.5% (tacrolimus) vs 69.2% (mycophenolate), not significant; serious infections more frequent with mycophenolate

Mycophenolate with glucocorticoid is standard induction and maintenance for active lupus nephritis. This Asian multicentre randomised trial assigned 130 patients with biopsy-proven class III or IV lupus nephritis, with or without class V, to tacrolimus (trough 6 to 8 ng/mL) or mycophenolate (1 g twice daily), each with glucocorticoid, as continuous treatment for 96 weeks.

Sustained renal response at 96 weeks was 58.5% with tacrolimus and 69.2% with mycophenolate, and complete remission 55.4% vs 63.1%; neither difference was statistically significant. At 48 weeks, response was 63.1% vs 66.2%. Overall adverse events were identical (80%), but the profiles differed: tacrolimus caused more acute kidney injury and tremor; mycophenolate caused more leucopenia, more treatment-related serious adverse events and more serious infections, and all three deaths were in the mycophenolate group.

For patients who cannot tolerate mycophenolate, have infection concerns, or plan pregnancy (when mycophenolate must be stopped), tacrolimus is a reasonable alternative backbone, with trough monitoring and attention to kidney function. The numerically lower response with tacrolimus, in a trial of 130 patients, means equivalence is not proven, and mycophenolate remains standard.

• Consider tacrolimus with glucocorticoid as an alternative to mycophenolate in lupus nephritis when mycophenolate is unsuitable.
• Target a tacrolimus trough of about 6 to 8 ng/mL and monitor creatinine for calcineurin-related kidney injury.
• Weigh infection risk; serious infections were more frequent with mycophenolate in this trial.
• Remember mycophenolate is teratogenic; tacrolimus may suit women planning pregnancy, with specialist input.

Why it matters

It gives randomised support for a tacrolimus-based option in a disease where mycophenolate is often limited by intolerance, infection or pregnancy.

Don't overread it

Not significant is not the same as equivalent; the trial does not show tacrolimus is as effective as mycophenolate.

The statistics, in plain English

A 10-point lower response rate with tacrolimus was not statistically significant, but with 65 patients per group the trial could miss a real difference of that size. Safety differences were clearer than efficacy differences.

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