New research findings indicate that weaning mycophenolate mofetil could be a safe practice in patients with stable SLE.

In a randomised controlled trial published in The Lancet Rheumatology, mycophenolate mofetil withdrawal in patients with quiescent SLE was not significantly inferior to continued maintenance therapy with the immunosuppressive.

After 6.6 years on mycophenolate mofetil therapy, weaning patients off of the drug over three months did not result in significantly increased rates of disease reactivation over 60 months compared with maintenance therapy, although there was a slight increase in flare risk, results showed.

For the multicentre, open-label study, patients aged between 18 and 70 years old with a clinical SLEDAI score of less than 4 at baseline on stable mycophenolate mofetil therapy were randomised to a withdrawal arm, in which the drug was tapered over 12 weeks, or a maintenance group, who continued taking their baseline dose for 60 weeks.

Researchers reported a 6-8% increase with upper 85% confidence limits spanning 11-19% in clinically significant disease reactivation and flare risk in the withdrawal versus maintenance arms.

“Clinicians can be reasonably confident that the actual increases in risks for the population range from 11% or lower for BILAG A to 19% or lower for any SELENA-SLEDAI flare,” they said.

“When considering mycophenolate mofetil withdrawal, clinicians and patients must decide if these upper limits fall within personal levels of acceptable risk”.

Of note, the team also found that the risk of disease activation was higher, and confidence limits wider, in patients with a history of renal involvement, although the difference was not statistically different when compared to the entire trial population.

“A recent study found that patients with lupus nephritis with low-grade histological activity are more likely than patients with normal biopsies to flare, following the withdrawal of maintenance immunosuppression, therefore it is possible that the increased clinically significant disease reactivation risk in individuals with a history of renal disease in our study could be due to a subset of patients with residual low-grade histologic activity,” the authors suggested.

There were several key limitations to the research, including its open-label design and thus the potential for clinician bias, and that inclusion criteria called for patients to be receiving stable doses of hydroxychloroquine, so results might differ for those not taking this drug.

However, “the data are clearly encouraging for several reasons”, wrote nephrologist Professor Noémie Jourde-Chiche, Hôpitaux Universitaires de Marseille Conception, and Dr Laurent Chiche, Specialist in Internal Medicine, Hôpital Européen de Marseille, France, in a linked editorial.

“First, they demonstrate the feasibility of weaning selected patients off immunosuppression after a few years of treatment and reaching disease quiescence. While the weaning of glucocorticoids is now a well-accepted goal in SLE, maintenance immunosuppressive therapy has mostly remained a long-term treatment to avoid relapses and organ damage until now.

“Second, the data provides a quantified risk assessment, enabling a shared medical decision with each patient. Last, the results pave the way for future studies to refine and secure this think-to-untreat strategy.”

According to the investigators, the research suggests that mycophenolate mofetil “could be safely withdrawn in patients with stable SLE”, but they also stressed that larger studies with a longer follow-up are still needed to confirm findings.