Effective plasma concentrations of mycophenolic acid and its glucuronide in systemic lupus erythematosus patients in the remission-maintenance phase

Mino, Yasuaki; Naito, Takafumi; Shimoyama, Kumiko; Ogawa, Noriyoshi; Kawakami, Junichi

doi:10.1111/j.1365-2710.2011.01269.x

Cited by 12 publications

(10 citation statements)

References 30 publications

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“…To investigate whether MMF reduced STAT3 phosphorylation, PBMCs from healthy individuals were stimulated with IL-6 and incubated with MPA for 3 hours at varying concentrations. Phosphoepitope flow analysis revealed a significant reduction in phosphorylated STAT3 following incubation with 10 μM MPA, a concentration equivalent to therapeutic levels found in SLE patients (19,20) (Figure 6A), with no differences observed in phosphorylated STAT5 ( Figure 6B) or cell apoptosis ( Figure 6C) after 3 hours. Furthermore, reductions in STAT3 phosphorylation were similar across all major cell populations ( Figure 6D).…”

Section: Figure 1 T-sne Analysis Pipeline Identifies 22 Phenotypicalmentioning

confidence: 74%

Mycophenolate mofetil reduces STAT3 phosphorylation in systemic lupus erythematosus patients

Slight-Webb¹,

Guthridge²,

Chakravarty³

et al. 2019

JCI Insight

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Section: Figure 1 T-sne Analysis Pipeline Identifies 22 Phenotypicalmentioning

confidence: 74%

Mycophenolate mofetil reduces STAT3 phosphorylation in systemic lupus erythematosus patients

Slight-Webb¹,

Guthridge²,

Chakravarty³

et al. 2019

JCI Insight

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“…For patients with autoimmune diseases, target MPA C trough of 0.9-3.0 lg/mL (Mino et al, 2012), 1.0-5.0 lg/mL (Roland et al, 2009) and 3.5-4.5 lg/mL (Neumann et al, 2008) have been proposed. According to the literature, in children with frequently relapsing nephrotic syndrome, MPA C trough value above 2-3 lg/mL is necessary to maintain disease remission (Fujinaga et al, 2007;Mendizábal et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Monitoring of mycophenolate mofetil metabolites in children with nephrotic syndrome and the proposed novel target values of pharmacokinetic parameters

Sobiak

Resztak

Ostalska‐Nowicka

et al. 2015

European Journal of Pharmaceutical Sciences

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“…In SLE, MMF, but not AZT or hydroxychloroquine, treatment has been associated with reduced frequency of switched memory B cells and modest decreases in levels of serum Ig and of anti‐dsDNA antibodies 40, 41, 42. The composition of B cell subpopulations may vary between individuals with SLE and after rituximab; repopulation appears to recapitulate ontogeny, perhaps further influenced by antigen stimulation 43.…”

Section: Discussionmentioning

confidence: 99%

Pragmatic Treatment of Patients With Systemic Lupus Erythematosus With Rituximab: Long‐Term Effects on Serum Immunoglobulins

Reddy

Martinez

Isenberg

et al. 2017

Arthritis Care & Research

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ObjectiveB cell–depletion therapy based on rituximab is a therapeutic option for refractory disease in patients with systemic lupus erythematosus (SLE). The aim of this observational study was to document long‐term effects on B cell function by following serum immunoglobulin levels in patients with SLE treated with rituximab in routine clinical practice.MethodsWe included 57 consecutive patients with SLE treated with rituximab and concomitant/sequential immunosuppressants and measured serum total IgG, IgM, and IgA and IgG anti‐dsDNA antibodies, over a median of 48 months most recent followup. Flow cytometry was used prospectively to assess B cell phenotypes in 17 of 57 patients.ResultsTwelve patients (21%) had persistent IgM hypogammaglobulinemia (<0.4 gm/liter), and 4 of 57 (5%) had low IgG (<7 gm/liter) at the most recent followup (range 12–144 months). This was not associated with serious adverse events or high anti–double‐stranded DNA (anti‐dsDNA) antibodies (>1,000 IU/ml; normal <50 IU/ml). Factors predictive of low serum IgM included baseline serum IgM ≤0.8 gm/liter (receiver operator curve analysis) and subsequent therapy with mycophenolate mofetil (MMF; odds ratio 6.8, compared with other immunosuppressants). In patients maintaining normal IgM levels (9 of 17), the frequency of circulating IgD+CD27+ B cells was significantly higher (P = 0.05). At 12 months after rituximab, 7 of 30 SLE patients with baseline anti‐dsDNA ≤1,000 IU/ml had lost seropositivity.ConclusionLower baseline serum IgM levels and sequential therapy with MMF were predictive of IgM hypogammaglobulinemia after rituximab in SLE, but this was not associated with higher levels of anti‐dsDNA antibodies or an increased risk of infections. This provides useful directions for clinicians regarding rituximab and sequential immunosuppressive treatment for patients with SLE.

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Effective plasma concentrations of mycophenolic acid and its glucuronide in systemic lupus erythematosus patients in the remission-maintenance phase

Abstract: MMF improved clinical laboratory markers and reduced prednisolone dosage in SLE patients with predose plasma concentration of MPA and MPAG in the interquartile ranges of 0·94-2·96 and 18·6-53·7μg/mL, respectively.

Cited by 12 publications

References 30 publications

Mycophenolate mofetil reduces STAT3 phosphorylation in systemic lupus erythematosus patients

Mycophenolate mofetil reduces STAT3 phosphorylation in systemic lupus erythematosus patients

Monitoring of mycophenolate mofetil metabolites in children with nephrotic syndrome and the proposed novel target values of pharmacokinetic parameters

Pragmatic Treatment of Patients With Systemic Lupus Erythematosus With Rituximab: Long‐Term Effects on Serum Immunoglobulins

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