A recent multicenter, randomized clinical trial published in JAMA Network Open has highlighted the potential of mycophenolate mofetil (MMF) in reducing the risk of severe flares in patients with new-onset systemic lupus erythematosus (SLE).
Participants were randomized to receive either prednisone and hydroxychloroquine (control group) or the same combination plus MMF for a period of 96 weeks. Results showed that patients receiving MMF experienced significantly fewer severe flares compared to those in the control group. Severe flare rates were 10.8% in the MMF group, compared to 27.7% in the control group. The incidence of lupus nephritis (LN), a serious complication of SLE, was also lower in the MMF group, with only 1.5% of patients developing LN compared to 13.8% in the control group.
MMF is an immunosuppressive agent widely recognized for its efficacy in transplant patients. It has also proven beneficial in managing lupus nephritis and various autoimmune disorders. Its effectiveness stems from its targeted action on T- and B-lymphocytes, leading to the suppression of both cell-mediated immune responses and antibody production. As a prodrug of mycophenolic acid (MPA), MMF works by inhibiting inosine-5′-monophosphate dehydrogenase, which depletes guanosine nucleotides in T and B lymphocytes. This inhibition curbs their proliferation, thereby dampening immune activity and reducing the formation of pathogenic antibodies.
MMF offers several significant benefits in the management of SLE, particularly in cases involving lupus nephritis. As a potent immunosuppressant, it effectively reduces inflammation and prevents damage to vital organs, especially the kidneys, by targeting the hyperactive immune response characteristic of lupus. One of its key advantages is its ability to serve as a steroid-sparing agent, allowing clinicians to lower steroid doses and reduce the associated long-term side effects, such as osteoporosis and increased infection risk. Additionally, mycophenolate generally has a more favorable safety profile compared to other immunosuppressants, leading to a lower incidence of severe side effects, such as infertility and bladder toxicity.
A 20-year study by Trevisonno et al. confirmed that MMF is highly effective in inducing complete or partial remission and preventing renal flares in lupus nephritis. Long-term maintenance therapy with MMF has been associated with a low flare rate and has proven to be safe, with minimal adverse effects. Over two decades of use in patients with SLE, no new safety concerns have emerged. MMF remains a reliable and well-tolerated option for long-term treatment, demonstrating its ability to prevent renal flares and minimize the progression to end-stage renal disease (ESRD).
Contrary, despite the positive results in the present study, adverse events, particularly infections, were common in both groups. The study findings suggest that while MMF can offer substantial benefits in reducing flares and protecting against LN, clinicians must carefully weigh the risks of potential side effects. This trial offers encouraging evidence for rheumatologists treating new-onset SLE, especially in patients with elevated anti-dsDNA antibodies. However, further research is needed to better understand the long-term implications of MMF use in this patient population.
References
- You Y, Zhou Z, Wang F, Li J, Liu H, Cheng X, Su Y, Chen X, Zheng H, Sun Y, Shi H, Hu Q, Xu J, Teng J, Yang C, Ye J. Mycophenolate Mofetil and New-Onset Systemic Lupus Erythematosus: A Randomized Clinical Trial. JAMA Netw Open. 2024 Sep 3;7(9):e2432131.
- Allison AC. Mechanisms of action of mycophenolate mofetil. Lupus. 2005;14 Suppl 1:s2-8.
- Trevisonno M, Hall A, Rosengarten S, Ginzler EM. Mycophenolate Mofetil for Systemic Lupus Erythematosus: Our 20-Year Experience. Cureus. 2023 Jan 30;15(1):e34413.