Tacrolimus and mycophenolate showed no significant difference in lupus nephritis response, with different side effects

Design

Prospective, multicentre, randomised trial in Asia, 96 weeks

Population

130 patients with biopsy-proven class III/IV lupus nephritis, with or without class V

Primary outcome

Sustained renal response at week 96

Effect

58.5% (tacrolimus) vs 69.2% (mycophenolate); complete remission 55.4% vs 63.1%; no significant difference

This Asian multicentre randomised trial enrolled 130 patients with biopsy-proven class III or IV lupus nephritis, with or without class V. Both groups (65 each) received intravenous methylprednisolone then oral prednisolone, plus either tacrolimus (trough target 6 to 8 ng/mL) or mycophenolate 1 g twice daily, as continuous induction and maintenance for 96 weeks. The primary end point was sustained renal response at week 96: more than 50% fall in proteinuria, eGFR of at least 60, and no flare or rescue therapy.

Sustained response was 58.5% with tacrolimus and 69.2% with mycophenolate, and complete remission 55.4% vs 63.1%; the differences were not significant. At week 48 the sustained response was 63.1% vs 66.2%. Adverse events were 80% in both arms. Acute kidney injury and tremor were more frequent with tacrolimus; leucopenia, treatment-related serious adverse events and serious infections were more frequent with mycophenolate. All three deaths were in the mycophenolate arm.

The numbers favour mycophenolate numerically on efficacy, but with 65 per arm the trial cannot show equivalence. Choice between the two rests on side-effect profile, drug levels and monitoring, patient preference and pregnancy plans.

• Sustained renal response at 96 weeks was 58.5% with tacrolimus and 69.2% with mycophenolate, not significantly different.
• Overall adverse events were 80% in both groups.
• Acute kidney injury and tremor were more frequent with tacrolimus.
• Leucopenia and treatment-related serious adverse events, including infections, were more frequent with mycophenolate.
• Choose between them on safety profile, monitoring capacity and patient factors, since efficacy did not differ significantly.

Why it matters

It shows that the two drugs trade different toxicities, which matters for choosing in a patient with pre-existing renal impairment, infection risk or tremor.

Don't overread it

The study was not powered to show equivalence, and the infection and death differences came from small numbers.

The statistics, in plain English

Not significantly different does not mean the same. With 65 patients per arm, the true difference could be anywhere from tacrolimus being considerably worse to being similar, which is why the authors describe the efficacy as showing no difference and the safety as different, rather than claiming equivalence.

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