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Delineating the clinical value of MMF for joint manifestations

Comment on: Five-years drug survival of mycophenolate mofetil therapy in patients with systemic lupus erythematosus: comparison between renal and non-renal involvement. Joint Bone Spine 2021 Jun 22;105246. doi: 10.1016/j.jbspin.2021.105246. Online ahead of print

Commented by: Thomas Dörner, Department of Medicine/Rheumatology and Clinical Immunology; Charite Universitätsmedizin Berlin, Germany

While MMF has not been approved for SLE, although recommended by EULAR and widely used as comparator or add-on in lupus nephritis, a recent representative study by Olivieri and colleagues evaluated its value in non-renal SLE in a retrospective analysis of 162 patients over five years.
A number of interesting observations were found. For a follow-up time of 5 years, those comprised a 60.5% retention rate in non-renal and 61.1% for lupus nephritis, respectively. Notably, MMF was preferentially prescribed for arthritis (24.1%) where the retention rate was 75.4% suggesting its clinical value for this organ manifestation as has also been suggested by prior studies. Discontinuation was most frequently found related to remission (21.7%) followed by loss of efficacy (20.5%). A limited evaluation for damage accrual over 12 months MMF treatment could not identify a substantial increase of the SDI in this cohort but warrants further studies.
The interesting lessons of this study are the confirmation that MMF appears to have an impact on non-renal manifestations, namely joint involvement where the retention rate is similar as for lupus nephritis. In addition, the potency of damage prevention remains of interest, although long-term follow-up studies need to address this more carefully.

Reference: Olivieri G, Ceccarelli F, Natalucci F, Pirone C, Orefice V, Pacucci VA, Garufi C, Truglia S, Spinelli FR, Alessandri C, Conti F. Five-years drug survival of mycophenolate mofetil therapy in patients with systemic lupus erythematosus: comparison between renal and non-renal involvement. Joint Bone Spine 2021 Jun 22;105246. doi: 10.1016/j.jbspin.2021.105246. Online ahead of print

A high burden of SLE risk genes is associated with persistent activation of the interferon system in patients with lupus.

25 May 2026

Comment on: Single-cell RNA-seq reveals a persistent interferon signature in immune cells from  systemic lupus erythematosus patients with high versus low polygenic risk scores despite antimalarial  treatment. J Autoimmun. 2026 May 12:161:103575. doi: 10.1016.  Commented by: Lars Rönnblom, Department of Medical Sciences, Uppsala University, Sweden.    Genome-wide association studies have identified more than 300 loci associated to increased risk for  SLE. For the majority of the gene variants in these loci the functional consequences in the SLE disease  process are unknown. However, a large proportion of identified risk genes are connected to the  interferon signaling pathway and contribute to the interferon signature in SLE. Calculating a polygenic  risk score (PRS) is a method to quantify the cumulative genetic burden in a single patient and studies  have shown that patients with a high PRS have a more severe disease phenotype with increased  organ damage and reduced survival, compared to individuals with a low PRS.   Antimalarial therapy is a well-established treatment of SLE and have shown efficacy in a large  proportion of patients. The therapeutic effect is partly mediated by down regulation of the activated  interferon system, which is connected to clinical response. However, despite therapeutic  concentrations of hydroxychloroquine, many patients still have flares and accumulation of organ  damage. The main objective of the present study was therefore to clarify if antimalarial treatment has  different effects in patients with a high or a low PRS.  SLE patients in remission with a high or a low PRS were compared in gene expression profile at single  cell level on peripheral blood mononuclear cells. A total of 6 healthy controls and 16 matched  patients treated with similar antimalarial doses, but no corticosteroids, were investigated. On  average, 9636 cells were analyzed from each donor and 2724 genes detected per cell. Despite similar  clinical picture, patients with a high PRS had a prominent interferon signature across multiple  immune cell types, compared to patients with a low PRS who had a weak expression of interferon  stimulated genes only in monocytes. Pathway analysis revealed that the interferon signaling pathway 

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