By Lucy Piper, medwireNews Reporter
medwireNews: Patients with systemic lupus erythematosus (SLE) may be able to stop taking mycophenolate mofetil once their condition becomes stable without significantly increasing their risk for flare compared with continuing treatment, suggests an open-label, randomized controlled trial.
“[M]ycophenolate mofetil withdrawal is desirable once disease quiescence has been achieved; however, if and when to do so has not been well-studied”, observe Judith James (Oklahoma Medical Research Foundation, Oklahoma City, USA) and colleagues.
They assessed mycophenolate mofetil withdrawal across 19 centres in the USA, involving 100 patients with SLE who had a clinical SLE Disease Activity Index (SLEDAI) score below 4 points, indicating quiescent disease, after a mean 6.6 years of mycophenolate mofetil treatment.
The participants were aged 42 years on average, most (84%) were women, 41% were White and 76% had a history of lupus nephritis. They were randomly assigned to a withdrawal group, whose mycophenolate mofetil treatment was tapered over a 12-week period or a maintenance group who continued to take the drug at their baseline dose of 1–3 g/day.
At week 60, 18% of 51 patients in the withdrawal group and 10% of 49 in the maintenance group had clinically significant disease reactivation.
This was defined as meeting the Safety of Estrogen in Lupus Erythematosus National Assessment (SELENA)–SLEDAI criteria for flare with a sustained increase in immunosuppressant therapy, comprising prednisone increased to 15 mg/day or more for at least 4 consecutive weeks, two or more short bursts of steroid treatment or the resumption or increase in the dose of mycophenolate mofetil or other immunosuppressant.
The rates of any and severe flares according to SELENA–SLEDAI criteria were a respective 49% and 16% among patients in the withdrawal group and 41% and 8% among those in the maintenance group. The findings were consistent when flares were defined as moderate or severe according to the British Isles Lupus Assessment Group 2004 Index B and A criteria, respectively.
The researchers calculated the Kaplan–Meier estimated risks of clinically significant disease reactivation to be 18% in the withdrawal group and 11% in the maintenance group, giving a nonsignificant increased risk of 7% with mycophenolate mofetil withdrawal, with an upper 85% confidence limit of 15%.
This meant that “mycophenolate mofetil withdrawal was not significantly inferior to mycophenolate mofetil maintenance” with regard to disease reactivation, James et al report in The Lancet Rheumatology.
They add that the increase in risk with mycophenolate mofetil withdrawal ranged from 6% to 8% for all flare endpoints with the upper 85% confidence limits ranging from 11–19%.
“When considering mycophenolate mofetil withdrawal, clinicians and patients must decide if these upper limits fall within personal levels of acceptable risks”, the investigators comment.
They also point out that the risk of flare endpoints with mycophenolate mofetil withdrawal was slightly higher (9–14%), and the 85% confidence limits wider (15–25%), in people with than without a history of renal involvement, but they were not significantly difference to those of the trial population as a whole.
Adverse events (AEs) of any grade were numerically lower among patients in the withdrawal group, occurring in 88% of patients versus 90% of those in the maintenance group, with corresponding rates of serious AEs of 10% and 14%. Infections were more frequent with maintenance than withdrawal, at a rate of 64% versus 46%.
“Our findings suggest that mycophenolate mofetil could be safely withdrawn in patients with stable SLE; however, larger studies with a longer follow-up are still needed”, write the authors.
In a related comment, Noémie Jourde-Chiche (Ai-Marseille University, France) and Laurent Chiche (Hôpital Européen de Marseille, France) support the need for rigorous evaluation of data from randomized controlled trials for an immunosuppressant weaning strategy, they have coined the term “think-to-untreat”.
They say the current findings are “clearly encouraging” and “pave the way for future studies to refine and secure this think-to-untreat strategy.”
They suggest possible future directions include more gradual weaning, the potential benefits of repeat renal biopsy to verify histological remission before proceeding to weaning and developing scores to monitor patients and predict those most likely to relapse.
News stories are provided by medwireNews, which is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group
Lancet Rheumatol 2024; doi:10.1016/S2665-9913(23)00320-X
https://pubmed.ncbi.nlm.nih.gov/38301682/
Lancet Rheumatol 2024; doi:10.1016/S2665-9913(24)00001-8
https://pubmed.ncbi.nlm.nih.gov/38301681/