Mycophenolate mofetil can be safely withdrawn in patients with stable lupus
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Key takeaways:
- Patients with systemic lupus erythematosus who withdrew had an 18% risk for disease reactivation vs. 11% among those who maintained.
- Infections were more common and more severe among those maintaining treatment.
Withdrawing mycophenolate mofetil therapy is not significantly inferior to maintenance treatment in patients with systemic lupus erythematosus who have achieved low disease activity, according to data published in The Lancet Rheumatology.
“Because of the significant toxicities and morbidities associated with long-term use, mycophenolate mofetil withdrawal is desirable once disease quiescence has been achieved,” Eliza F. Chakravarty, MD, of the Oklahoma Medical Research Foundation, and colleagues wrote in The Lancet Rheumatology. “However, if and when to do so has not been well-studied.”
To better understand the effects of mycophenolate mofetil withdrawal in stable SLE, Chakravarty and colleagues conducted an open-label, randomized trial across 19 U.S. centers. Between Nov. 6, 2013, and April 27, 2018, the researchers recruited 102 adult patients with SLE who were using mycophenolate mofetil (mean age, 42 years [SD = 12.7]; 84% women). Participants had demonstrated quiescent disease, defined as a clinical SLE Disease Activity Index score of less than 4, and were on long-term stable or decreasing mycophenolate mofetil therapy.
Included patients were randomly assigned to either taper mycophenolate mofetil over 12 weeks (n = 52) or maintain a baseline dose of 1 g to 3 g per day for 60 weeks (n = 50). Standardized SLE disease assessments were taken at baseline, monthly to week 24, then at weeks 32, 40, 48 and 60. The primary endpoint was clinically significant disease reactivation after 60 weeks, defined as any flare calling for a sustained uptick in immunosuppressive therapy, with secondary endpoints including flare severity and time to disease reactivation.
Overall, 88% of the maintenance group and 94% of the withdrawal group completed all 60 weeks of the study. During that time, the withdrawal group faced an 18% (95% CI, 10-32) risk for clinically significant disease reactivation, while the maintenance group’s risk was 11% (95% CI, 5-24), according to the researchers. Clinically significant disease reactivation was reported in 18% of the withdrawal group and in 10% of the maintenance group.
In addition, rates of adverse events were similar between the two groups, with 45 maintenance-group participants experiencing 189 total events vs. 46 withdrawal-group participants demonstrating 205 events. However, the maintenance group saw a higher rate of infections — 64% vs. 46% in the withdrawal group — as well as more severe infections.
“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,” Chakravarty and colleagues wrote, adding that these findings “should not be considered appropriate to extrapolate to all patients with SLE taking mycophenolate mofetil.”
“Patients and clinicians should be informed of the slight increase in flare risk to aid treatment decisions,” they added.
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
If we have success with a treatment regimen in rheumatology practice, we tend to stick with it. Tapering a patient off of a successful treatment, with the exception of corticosteroids, is generally avoided. So, should mycophenolate mofetil (MMF) be withdrawn after successfully treating the patient?
I had a late-middle aged white male patient with lupus and renal involvement, who did extremely well with MMF for years until he developed progressive multifocal leukoencephalopathy (PML). A colleague here in Alabama has also seen PML in a female patient with lupus on MMF. PML is a rare demyelinating brain disorder triggered by the JC virus, a ubiquitous polyomavirus.
PML typically emerges in the presence of underlying immunosuppression, with acquired immune deficiency syndrome (AIDS) being the most prevalent predisposing condition. FDA “black box” warnings for PML are found on natalizumab (Tysabri, Biogen Idec), efalizumab (Raptiva; Genentech, Merck/EMD Serono), rituximab (Rituxan, Genentech), mycophenolate mofetil and brentuximab vedotin (Adcetris, Seagen).
To be susceptible to developing PML, a patient needs to be infected with JC virus. It is generally acknowledged that there is a seroprevalence of greater than 50% among the adult population for JC virus. However, despite the high prevalence rate of JC virus, PML is an extremely rare disorder. The correlation between PML and B-cell malignancies, like chronic lymphocytic leukemia and Hodgkin's disease, as well as disorders linked to B-cell activation such as systemic lupus erythematosus and AIDS, heightens the risk factors for PML development.
Although PML due to MMF is rare (14.4 cases per 100,000 in renal transplant patients), there are other long-term MMF treatment adverse events, including heightened risks for infection, malignancies, impaired vaccine responses, severe birth defects, and miscarriage. These adverse drug reactions underscore the necessity of withdrawing MMF following disease quiescence.
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