Months Of Mycophenolate Mofetil Treatment Research Articles

Assessment of the Potential Impact of Mycophenolate Mofetil on Lowering Renal Biomarkers in Patients with Class III Lupus Nephritis: A Pilot Study to Predict Renal Function Progress

Abstract Background: Lupus nephritis (LN) is a potentially severe complication of systemic lupus erythematosus (SLE). Mycophenolate mofetil (MMF) is an oral immunosuppressive agent used in lupus patients who are intolerant of or refractory to other conventional therapies. The aim of this study was to assess the potential effect of MMF on lowering some biomarkers as a predictive of renal function in patients with Class III LN. Methods: This was a single-center, prospective cohort study that enrolled patients with Class III LN who received 2 g/day of oral MMF. The potential impact of MMF on renal biomarkers was evaluated at baseline and subsequently at 3-month intervals for 6 months according to changes in antinuclear antibodies (ANA), antidouble stranded deoxyribonucleic acid (anti-dsDNA), elastase α-1 proteinase inhibitor (α-1 PI), proteinuria, and the urine protein-to-creatinine ratio (P/C ratio). Results: A significant decrease over the course of MMF treatment compared to the baseline regarding ANA (1.37 ± 0.47 vs. 2.90 ± 1.05, P = 0.03); anti-dsDNA (23.39 ± 3.19 vs. 39.91 ± 8.1 IU/mL, P = 0.02); elastase α-1 PI (512.4 ± 74.12 vs. 696.35 ± 105.35 ng/mL, P = 0.03); proteinuria (0.25 ± 0.44 vs. 1.95 ± 0.76 g/24 h., P = 0.01); and P/C ratio (0.20 ± 0.22 vs. 1.37 ± 0.26, P = 0.04). Conclusion: MMF is effective in lowering renal biomarkers of Class III LN revealed by a significant reduction in ANA, anti-dsDNA, elastase α-1 PI, proteinuria, and P/C ratio over 6 months of MMF treatment.

Mycophenolate Mofetil Treatment in Childhood Steroid-sensitive Nephrotic Syndrome: Single Center Experience

Objective : We aimed to investigate the efficacy of mycophenolate mofetil (MMF) for maintaining remission and reduce the number of relapses in childhood steroid-sensitive nephrotic syndrome. The effects of MMF on growth and blood pressure parameters were also evaluated. Material and Methods: This retrospective, single-center observational study included patients with steroid-sensitive nephrotic syndrome who were treated using MMF between 2009 and 2019 in the Department of Pediatric Nephrology in our hospital. Results: Ten patients had steroid-dependent nephrotic syndrome; six patients frequently had relapsing nephrotic syndrome in this study. The mean duration of the disease was 93.3 ± 25.0 months and the mean duration of the MMF onset was 33.9 ± 16.7 months after diagnosis. Ten patients showed a 50% or greater reduction in the relapse rate and the prednisolone treatment was discontinued in eight patients for six months or more. Compared to the previous year, before the start of the MMF treatment, there was a 52.7% reduction in the relapse rate and a 36.6% reduction in the cumulative annual dose of steroid after 12 months of MMF treatment. The height z score and the median office systolic blood pressure standard deviation scores of the patients improved after MMF treatment (respectively p = 0.003, p = 0.01). Conclusion: The findings suggest that MMF may lead to decreased relapse rates and cumulative steroid dose, which has a positive effect on growth and blood pressure parameters in steroid-sensitive nephrotic syndrome.

Mycophenolic acid area under the curve is associated with therapeutic response in pediatric lupus nephritis

Introduction Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is an effective treatment in lupus nephritis. Therapeutic drug monitoring studies of MMF suggest that area under the concentration-time curve (AUC) values of MPA of 30–45 mg.h/L may be associated with better outcome in adults with lupus but data in children is scarce. Methods In this retrospective study, 27 children were treated with MMF for biopsy proven class III–IV–V lupus nephritis between 2009 and 2016. AUC of MPA was determined on the basis of sampling times at 20, 60, and 180 minutes post-dose using a Bayesian estimator. In 25 children, AUC was performed within 6 months after kidney biopsy and MMF initiation. Treatment response at 6 months of MMF treatment was defined as follows: normal or improved GFR by 25% compared to baseline, 50% reduction of proteinuria resulting in a level Results In total, 62 AUC of MPA were analyzed [median 44 mg.h/L (IQR 33–54)] in 27 patients. The findings indicate individual dose adaptation in 32 cases (52%) to achieve an AUC target of 30–60 mg.h/L. At 6 months, 14/25 patients were defined as responders (56%) with a median AUC value of 49 [40–59] and 11/25 as non-responders (44%) with a median AUC value of 29 [24–38]. Patients with MPA AUC levels of > 45, 30–45, and 45 was significantly associated with therapeutic response (OR 3.9, 95% CI 2.4–10.5, P Conclusion Therapeutic drug monitoring leading to individualize dosing may improve the efficacy of MMF. An AUC of MPA > 45 mg.h/L is associated with a better response rate and may be considered as a target value in paediatric lupus nephritis.

Efficacy of mycophenolate mofetil in severe mucocutaneous lichen planus: a retrospective review of 10 patients

Ulcerative lichen planus is an uncommon and severe subtype of lichen planus primarily affecting the oral mucosal surfaces. It may be associated with significant morbidity and often requires immunosuppressive therapy to achieve disease control. There have been no previous reports in which objective outcome measures have been used to assess the efficacy of mycophenolate mofetil (MMF) in severe ulcerative lichen planus. To evaluate the clinical responses of patients with severe ulcerative oral lichen planus who were treated with MMF at a tertiary oral medicine/dermatology centre. This was a retrospective review of oral disease severity scores performed in 10 patients with recalcitrant ulcerative oral lichen planus (vulvovaginal-gingival, n = 8; penogingival, n = 1; oral, n = 1) before and after treatment with MMF therapy. The results were analysed using the Wilcoxon matched pairs signed-rank test. The mean duration of MMF treatment was 3·7 (SD ± 2·4) years with a mean follow-up of 4·2 (SD ± 2·7) years. The mean baseline oral disease severity scores (39·1 ± 11·9) improved by 40% after 12-15 months (24·3 ± 11·9, n = 8, P = 0·01) and by 43% after 21-24 months of MMF treatment (22·2 ± 10·4, n = 9, P = 0·01). Of the 10 patients, six achieved remission, one had well-controlled disease and three had partially controlled disease. Two patients who achieved remission successfully discontinued treatment. MMF was well tolerated in all patients. Our case series demonstrates the efficacy and favourable side-effect profile of MMF in the treatment of severe ulcerative lichen planus.

Long-term, maintenance MMF monotherapy improves the fibrosis progression in liver transplant recipients with recurrent hepatitis C

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (LT) is universal. We designed a retrospective case-control study to evaluate the effect of mycophenolate mofetil (MMF) monotherapy in patients with recurrent hepatitis C. Fifteen patients with histologically proven hepatitis C recurrence after LT were switched from calcineurin inhibitors (CNIs) to MMF monotherapy because of impairment of kidney function and/or metabolic side effects, and treated for 48 months (MMF group). Fifteen well-matched LT recipients who continued to receive CNIs therapy over the same period served as control group. Demographics, clinical data, time after LT, and baseline liver biopsies were similar in the two groups. There was no worsening of hepatic fibrosis during the study in the MMF group [2.6 ± 1.5 (baseline) Ishak Units vs. 2.7 ± 1.8 (after 48 months of MMF treatment), P = 0.6]. In contrast, a significant increase in the fibrosis score [2 ± 1.1 (baseline) vs. 3.2 ± 1.7 (after 48 months of CNI treatment), P = 0.0002] was observed in the control group. The yearly fibrosis progression rate was of 0.05 ± 0.44 in the MMF group and 0.33 ± 0.24 in the CNI group (P = 0.04). MMF monotherapy is associated with a favourable effect on hepatic fibrosis progression in HCV liver transplant recipients.

Delayed severe pneumonia in mycophenolate mofetil-treated patients with IgA nephropathy

Mycophenolate mofetil (MMF), a relatively new immunosuppressant, is widely used in the field of transplantation and also for autoimmune diseases with good tolerance. It has been reported that MMF possesses potent activity against pneumocystis pneumonia (PCP). This study investigated the effects of this treatment on the occurrence of severe pneumonia (SP) including PCP and its risk factors. This was a retrospective cohort study. Of 850 IgA nephropathy (IgAN) patients that were followed up in our renal centre, 32 received MMF (1-1.5 g/day) and 47 were treated with cyclophosphamide (CTX; 50-100 mg/day). All the patients also received prednisone. SP was defined as diffuse bilateral lung infiltrate with respiratory failure, and PCP was diagnosed by detecting organisms in sputum and bronchoalveolar lavage. Patients given MMF or CTX did not differ in their distribution of age, sex, renal function or prednisone dosage. However, 6 of the 32 patients developed SP around the third month after the initiation of MMF administration: 3 were diagnosed with PCP, 2 with suspected PCP and in the other PCP could not be excluded. SP did not occur in patients treated with CTX. Most SP cases (five of six) presented with abrupt onset and rapidly progressed to respiratory failure, from which four died. The deterioration of renal function was strongly associated with the occurrence of SP. Six patients (6 of 16) with chronic renal function impairment (eGFR < 60 ml/min/1.73 m(2)) developed SP while none of the patients with eGFR > 60 ml/min/1.73 m(2) did. Absolute lymphocyte counts decreased significantly in patients with eGFR < 60 ml/min/1.73 m(2) after 3 months of MMF treatment compared to the counts before MMF was initiated (1.71 +/- 0.23 versus 2.43 +/- 0.17 x 10(9)/l, P = 0.04). This effect was more pronounced in patients with SP, which had significantly lower counts than patients without SP (0.22 +/- 0.04 versus 1.91 +/- 0.20 x 10(9)/l, P = 0.001). The occurrence of SP or PCP in patients with chronically impaired renal function was also associated with lymphopenia. This study is the first report of delayed SP including PCP following MMF plus corticosteroids in patients with IgAN. Chronically impaired renal function might be a risk factor for severe infection, and lymphocyte counts may serve as useful and convenient tools for monitoring the intendance of the occurrence of PCP. This finding and its risk factors need to be further evaluated.

Mycophenolate mofetil as adjunctive therapy for MMN patients: a randomized, controlled trial

Multifocal motor neuropathy (MMN) is an immune-mediated disorder characterized by slowly progressive asymmetrical limb weakness. Treatment with immunoglobulins (IVIg) leads to improvement of muscle strength. Anecdotal evidence suggests that immunosuppressive drugs as adjunctive therapy may be beneficial. Mycophenolate mofetil (MMF) is a potent and safe immunosuppressant. Safety and efficacy of MMF as adjunctive therapy for MMN patients receiving IVIg maintenance treatment were evaluated in a randomized controlled trial. MMN patients responding to IVIg treatment were eligible for randomization. Muscle strength and functional status were assessed at monthly intervals for 1 year. Three months after the start of MMF or placebo treatment, IVIg doses were reduced stepwise, until a deterioration of functioning or decline in muscle strength could be observed. An IVIg dose reduction of 50% during adjunctive treatment was defined as a primary endpoint. Secondary outcome measures were improvement in muscle strength and functional status after 3 months and reduction of anti GM1-IgM titres after 12 months of MMF treatment. Twenty-eight patients were randomized. One patient allocated to MMF reached the primary endpoint of 50% IVIg dose reduction. After 12 months IVIg reduction did not differ significantly between the two treatment groups. Patients did not experience drug toxicity and none of the patients showed significant disease progression after 12 months. Muscle strength and functional scores after 3 months and anti GM1-IgM titres after 12 months did not change. Adjunctive treatment of MMN patients with MMF at a dose of 1 g twice daily is safe but does not alter disease course or allow significant reduction of IVIg doses.

Mycophenolate mofetil introduction stabilizes and subsequent cyclosporine A reduction slightly improves kidney function in pediatric renal transplant patients: A retrospective analysis

Chronic allograft nephropathy (CAN) is the major cause of late graft loss. Among others, chronic calcineurin inhibitor toxicity (CNI) contributes to the development of CAN. Therefore, reduction in CNI dosage may delay the development of CAN, leading to longer graft survival. It was the aim of the present retrospective analysis to investigate the effect of mycophenolate mofetil (MMF) addition with subsequent cyclosporine A (CSA) reduction on renal function in pediatric kidney allograft recipients. Seventeen patients (aged 8.3-17.6 yr) with monotherapy with CSA and progressive loss of renal function at a median of 3.4 yr after kidney transplantation were enrolled. After at least three months of MMF treatment, CSA dosage was stepwise reduced to trough levels of 100, 80, and 60 ng/mL. In all patients, introduction of MMF prevented a further decrease of glomerular filtration rate (GFR). The mean GFR 12 months before study enrollment was 96.1+/-24.5 and 71.0+/-21.0 mL/min/1.73 m2 at start of MMF. After introduction of MMF and unchanged CSA dosage GFR was stabilized to 71.1+/-23.8 mL/min/1.73 m2. After CSA reduction to trough levels of 60 ng/mL, GFR was slightly ameliorated up to 76.3+/-24.1 mL/min/1.73 m2. Within the follow-up period, one borderline rejection occurred in a patient in whom the CSA trough level was 60 ng/mL since seven months. In pediatric kidney allograft recipients with progressive loss of renal function reduction of CSA after introduction of MMF may stabilize and even slightly ameliorate renal function.

Mycophenolate Mofetil for Renal Dysfunction after Pediatric Liver Transplantation

Cyclosporine A (CsA) and tacrolimus (Tac) provide effective immunosuppression after orthotopic liver transplantation (OLT) but can cause renal dysfunction that may progress to end-stage renal failure (ESRF). Mycophenolate mofetil (MMF) is a newer immunosuppressant that does not affect renal function. Its long-term use in children with renal dysfunction after OLT has not yet been fully evaluated. A retrospective analysis was performed of all children begun on MMF for renal dysfunction and followed up for at least 1 year. Renal dysfunction was defined as calculated glomerular filtration rate (cGFR) of less than 65 mL/min/1.73 m2. cGFR and liver function were measured before and after transfer. Data were analyzed using the Wilcoxon signed rank test. Forty-eight children (23 males) began MMF at a median age of 11.1 (0.9-18.1) years and at a median of 4.0 (0.3-12.4) years postOLT. Median baseline cGFR was 54 (range 29-65) mL/min/1.73 m2. Immunosuppression after transfer was MMF monotherapy in 36, MMF with steroids, in 4 and MMF with low-dose CsA or Tac in 8. In 44 (92%) patients, there was a statistically significant increase to a median cGFR of 69 (28-114) mL/min/1.73 m2 by 1 month and a further increase to a median cGFR of 77 (24-105) mL/min/1.73 m2 by 2 months of MMF treatment, after which time cGFR was maintained. Children aged less than 3 years at OLT or who were less than 5 years postOLT when MMF was begun demonstrated greater increases in cGFR. Four children with a median baseline cGFR of 34 (range 31-49) mL/min/1.73 m2 did not respond and progressed to ESRF. Mild side effects occurred in seven (15%) and gastrointestinal bleeding requiring discontinuation of MMF in one (2%). Liver function abnormalities occurred in seven (15%): transient transaminitis in three, acute rejection in two, and chronic rejection in two, of whom one required retransplantation. In 92% children with renal dysfunction after OLT, MMF treatment provided safe and effective immunosuppression and allowed CsA or Tac to be discontinued or reduced, leading to improvement of renal function. The improvement was greatest in younger children and those who began MMF early postOLT. Side effects were uncommon. Additional steroid cover during the transfer to MMF should be considered to prevent liver-allograft rejection.