Mycophenolate Mofetil Group Research Articles

Sirolimus vs mycophenolate mofetil (MMF) in primary combined pancreas and kidney transplantation. Results of a long-term prospective randomized study.

The study was intended to compare pancreas graft survival rates in two groups of pancreas and kidney transplant recipients prospectively randomized to treatment either with sirolimus or MMF. From 2002 to 2013, 238 type 1 diabetic recipients with end-stage kidney disease were randomized 1:1 to sirolimus or MMF treatment. Noncensored pancreas survival at 5years was 76.4 and 71.6% for sirolimus and MMF groups, respectively (P>.05). Death-censored pancreas survival was better in the sirolimus group (P=.037). After removal of early graft losses pancreas survival did not differ between groups (MMF 83.1% vs sirolimus 91.6%, P=.11). Nonsignificantly more grafts were lost due to rejection in the MMF group (10 vs 5; P=.19). Cumulative patient 5-year survival was 96% in the MMF group and 91% in the sirolimus group (P>.05). Five-year cumulative noncensored kidney graft survival rates did not statistically differ (85.6% in the sirolimus group and 88.8% in MMF group). Recipients treated with MMF had significantly more episodes of gastrointestinal bleeding (7 vs 0, P=.007). More recipients in the sirolimus group required corrective surgery due to incisional hernias (21 vs 12, P=.019). ClinicalTrials No.: NCT03582878.

Long-Term Treatment With Azathioprine and Mycophenolate Mofetil for Myositis-Related Interstitial Lung Disease

The efficacy of azathioprine (AZA) and mycophenolate mofetil (MMF) for interstitial lung disease (ILD) has been described, but mainly in connective tissue disease-associated ILD. The objective of this study was to evaluate the effect of AZA and MMF on lung function and prednisone dose in myositis-related ILD (M-ILD). In this retrospective study, patients with M-ILD seen at Johns Hopkins and treated with AZA or MMF and no other steroid-sparing agents were included. Linear mixed-effects models adjusted for sex, age, antisynthetase antibody, and smoking status were used to compare the change in FVC %predicted, diffusing capacity of the lungs for carbon monoxide (Dlco) %predicted, and prednisone dose. Sixty-six patients with M-ILD were treated with AZA and 44 with MMF. At treatment initiation, mean FVC %predicted and Dlco %predicted were significantly lower in the AZA group than in the MMF group. In both groups, FVC %predicted improved and the prednisone dose was reduced over 2 to 5 years; however, for Dlco %predicted, only the AZA group improved. The adjusted model showed no significant difference in posttreatment FVC %predicted or Dlco %predicted between groups (mean difference of 1.9 and -8.2, respectively), but a 6.6-mg lower dose of prednisone at 36months in the AZA group. Adverse events were more frequent with AZA than MMF (33.3%vs13.6%; P= .04). In M-ILD, AZA treatment was associated with improved FVC %predicted and Dlco %predicted, and lower prednisone dose. Patients treated with MMF had improved FVC %predicted and lower prednisone dose. After 36months, patients treated with AZA received a lower prednisone dose than those treated with MMF.

PS1543 RELIEVING IMMUNOSUPPRESSION IMPROVES VΔ2+ T CELLS RECOVERY AND DECREASES EBV REACTIVATION AFTER HEMATOPOIETIC TRANSPLANTATION

Background:Immunosuppressive drugs have been widely used for transplantation over the last decade. Mycophenolate mofetil (MMF) and cyclosporine A (CsA) are usually used to prevent and treat graft‐versus‐host disease (GVHD) in the context of hematopoietic stem cell transplantation (HSCT). With the numerous studies reported the clinical efficacy of immunosuppressants, attentions for their side effects, such as opportunistic infections, are increasing. Epstein–Barr virus (EBV) reactivation and its related diseases are the common threats with high mortality after haploidentical HSCT (haploHSCT). Although the immunosuppression was associated with EBV infection after solid organ transplantation, this correlation has been less reported in the scenario of hematopoietic transplantation. We previously showed that recovery of Vδ2+ T cells inversely correlated to EBV reactivation after haploHSCT and Vδ2+ T cells isolated from haploHSCT recipients were not expanded by aminobisphosphonates stimulation. The influence of immunosuppressants on the Vδ2+ T cells recovery and anti‐EBV cytotoxicity post‐HSCT are unknown.Aims:To investigate the impacts of immunosuppressive drugs on the Vδ2+ T cells expansion and function, and whether relieving the immunosuppression can improve Vδ2+ T cells recovery and decrease EBV reactivation in the setting of allogeneic HSCT.Methods:Mycophenolic acid (MPA) is an active form of MMF and usually used in the in‐vitro functional experiments. Pamidronate was used to trigger the expansion of Vδ2+ T cells in peripheral blood mononuclear cells isolated from healthy donors, with or without immunosuppressants (MPA and CsA). The activation, proliferation, functional receptor expression, cytokines production, and EBV‐specific cytotoxicity of Vδ2+ T cellswere detected by flow cytometry. This study also included a cohort of 165 patients undergoing haploHSCT. These patients were divided into 2 groups based on the different courses of MMF administration for GVHD prophylaxis. The recoveries of T‐cell subsets and incidences of EBV reactivation were statistically compared.Results:Peripheral Vδ2+ T cells from healthy donors were dramatically expanded by pamidronate stimulation for 10 days, with the percentage of Vδ2+ T cells in total MNCs was increased from 2.8% to 89%. In contrast, MPA and CsA treatment profoundly attenuated this expansion given that Vδ2 cells levels were even lower than baseline under the same condition. The activation (expression of CD25) and IFN‐γ production of Vδ2 cells were inhibited while NKG2D expression was moderately decreased by both drugs. Consistently, EBV‐specific cytotoxicity of Vδ2 cells were also impaired after treatment with MPA and CsA. The recoveries of T‐cell subsets were monitored in patients with different courses of MMF following haploHSCT. Recoveries of other detected T‐cell subpopulations at day 30 were significantly faster in the shorter MMF group than the longer MMF group. The level of Vδ2 cells was continuously increased from 30 to 90 days post‐haploHSCT after reducing the course of MMF, accompanied with a decreased incidence of EBV reactivation. Day‐30 Vδ2 levels remained an independent factor for EBV reactivation in patients with different MMF durations.Summary/Conclusion:Reliving the suppression of MMF and CsA is favorable to anti‐EBV immunity probably through recovering Vδ2 cells expansion and function. These findings will help improve the outcome of hematopoietic transplant.

Efficacy and Safety of Mizoribine Combined With Tacrolimus in Living Donor Kidney Transplant Recipients: 3-Year Results by a Chinese Single Center Study

BackgroundMizoribine (MZR) was effective and safe for living Chinese donor kidney transplantation (LDKT) on tacrolimus-based treatment 1 year after transplantation. We investigated whether MZR was effective and safe for LDKT on tacrolimus-based treatment with long follow-up periods. MethodsWe compared 22 LDKT recipients who were administered MZR, tacrolimus, and corticosteroids with a control group (n = 20) treated with mycophenolate mofetil (MMF), tacrolimus, and corticosteroids. Primary efficacy endpoints were 3-year patient survival, 3-year graft survival, and acute rejection (AR) rate within 3 years after transplantation. ResultsThe 3-year patient and graft survival rates for the MZR and MMF groups were 100%. The AR rate after transplantation was 18.2% for the MZR group and 10.0% for the MMF group; the difference was not significant (P = .665). There was no significant difference in serum creatinine levels, glomerular filtration rates (eGFR), serum urate levels, blood urea nitrogen, and cystatin C levels 12, 24, and 36 months after transplantation. No significant differences in the CD3, CD4, CD8, CD4/CD8, and CD45 were observed between the 2 groups 12, 24, and 36 months after transplantation. There were no significant differences in adverse events among the MZR or the MMF group, whereas the prevalence of gastrointestinal symptoms were significantly lower in the MZR treatment group (P = .003), especially acid reflux (P = .007). Compared with the MMF group, the MZR group should lighten the burden on patients. ConclusionMZR with tacrolimus and corticosteroids provides satisfactory immunosuppression and higher safety for Chinese LDKT over a 3-year follow-up.

Delay expression of NKp30 on NK cells correlates with long-term mycophenolate mofetil treatment and higher EBV viremia post allogenic hematological stem cells transplantation

Mycophenolate mofetil (MMF) is an immunosuppressive agent that is widely used in graft-versus-host disease prophylaxis because of its inhibitory function on T cells and B cells. However, the effect of MMF on natural killer cell reconstitution after allogenic hematological transplantation is largely unknown. The present study examined the effects of different MMF administration durations after haploidentical allo-HSCT on NK cell reconstitution. Ninety patients were enrolled in this study and defined into two groups in term of MMF duration. We found that MMF patients in the long-term MMF group were associated with a poor reconstitution of NK cells and a significantly lower cytotoxicity from day 30 to day 180 post-transplantation. Especially, the long-term MMF group inhibits reconstitution of NKp30 NK subsets, which correlated with higher risk of EBV viremia. Multivariate analysis showed that a better reconstitution of NKp30 cells was associated with lower EBV viremia (HR0.957, p = .04). In vitro experiments demonstrated that the active metabolite of MMF, mycophenolic acid (MPA), inhibited the proliferation and cytotoxicity of NK cells from healthy donors or patients at day 30 post-transplantation. In summary, our findings demonstrated that long-term MMF administration delayed the quality and quantity of NK cells, especially NKp30 subpopulations, which was associated with decreased EBV viremia post allogeneic HSCT.

Efficacy and safety of tacrolimus in induction therapy of patients with lupus nephritis.

BackgroundThe purpose of this study was to detect the efficacy and safety of tacrolimus (TAC) in induction therapy of patients with lupus nephritis.MethodsAssociated studies were extracted from the PubMed and the Cochrane Library on July 10, 2018, and applicable investigations were pooled and analyzed by meta-analysis. Data on complete remission (CR), total remission (TR; complete plus partial remission), proteinuria levels, urine erythrocyte number, albumin, glomerular filtration rate, negative rate of ds-DNA, C3 levels, C4 levels, systemic lupus erythematosus disease activity index (SLE-DAI), etc, were extracted and pooled using RevMan 5.3.ResultsIn the therapeutic regimen of TAC + glucocorticoids (GC) vs cyclophosphamide (CYC) + GC, the results indicated that the TAC group had high values of CR, TR, albumin, and negative rate of ds-DNA, and low values of proteinuria levels and SLE-DAI when compared with those in CYC group (all P<0.05). In the therapeutic regimen comprising TAC + GC vs mycophenolate mofetil (MMF) + GC, the results indicated that the difference of CR, TR, proteinuria levels, and albumin between TAC group and MMF group were not significant (all P>0.05). In the therapeutic regimen comprising TAC + MMF + GC vs CYC + GC, multitarget therapy group showed higher values of CR, TR, urinary protein decline, and rise of serum albumin when compared with CYC group (all P<0.05).ConclusionTAC is an effective and safe agent in induction therapy of patients with lupus nephritis.

Maintenance therapy for lupus nephritis with mycophenolate mofetil or azathioprine. A meta-analysis .

Maintenance therapy for lupus nephritis (LN) remains controversial. This meta-analysis of randomized controlled trials (RCTs) describes the comparative benefits and safety of mycophenolate mofetil (MMF) versus azathioprine (AZA) as maintenance therapy in patients with LN. RCTs that compared the maintenance regimens of MMF and AZA in the treatment of LN were included. Outcomes were mortality, end-stage renal disease (ESRD), renal relapse, doubling of serum creatinine, and adverse effects. We performed the meta-analysis using Review Manager software (version 5.3). Seven RCTs were included in the meta-analysis. There were no significant differences between the MMF and AZA groups in regards to mortality, relapse, ESRD, doubling of serum creatinine, infection, or gastrointestinal upset. However, the MMF group incurred lower risks of leukopenia (RR = 0.16, 95% CI = 0.06 - 0.40; p = 0.0001) and amenorrhea (RR = 0.23, 95% CI = 0.09 - 0.59, p = 0.002) compared with the AZA group. MMF seems more effective than AZA as maintenance therapy for LN although the differences did not reach statistical significance. Furthermore, the MMF group incurred lower risk of leukopenia than AZA. However, more RCTs are needed to confirm the conclusion.

Efficacy of mycophenolate mofetil in Japanese patients with systemic lupus erythematosus.

To assess the renal and non-renal efficacy of mycophenolate mofetil (MMF) in Japanese patients with systemic lupus erythematosus (SLE). We conducted a retrospective study to assess the renal and non-renal efficacies of MMF in Japanese patients with systemic lupus erythematosus (SLE). We analyzed 14 patients with lupus nephritis (LN) who were given MMF, and 13 patients who received monthly intravenous cyclophosphamide (IVCY) as induction therapy, and a further 19 patients without LN who were treated with MMF, and 13 patients who took tacrolimus (TAC) to reduce glucocorticoid dosages. We assessed the therapeutic effects of each therapeutic regime on renal and non-renal disease manifestations over a six-month period after treatment initiation. Median urine protein to creatinine ratios in the MMF and IVCY groups significantly decreased from 2.2 to 0.7g/gCr and from 3.3 to 0.5g/gCr, respectively. Significant improvements in serum immunological variables (serum complements C3 and C4 and the anti-double stranded DNA antibody) and reductions in the SLE disease activity index (SLEDAI) and daily prednisolone dosages were observed in each group with LN. MMF and TAC significantly improved SLEDAI and serum immunological variables and reduced daily prednisolone dosages in patients without LN. The present results demonstrated that MMF might be an effective treatment for renal and non-renal manifestations in Japanese patients with SLE and has potential as a good therapeutic alternative and steroid-sparing agent.

Changing landscape of immunosuppression in ANCA-associated vasculitis

Over last decades, there have been substantial advances in the immunosuppressive treatment for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), that is, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). The...

Short Course Mycophenolate Mofetil Yields Adequate Immune Reconstitution and Equivalent Alloreactivity Following Allogeneic Hematopoietic Stem Cell Transplantation

Clinical outcomes following hematopoietic cell transplant (HCT) are considered stochastic with different outcomes despite uniformity in characteristics between patients. However, immune reconstitution following SCT has features of a dynamical system, making it likely that clinical outcomes are partially deterministic. We hypothesized that early cessation of mycophenolate mofetil (MMF) in reduced intensity conditioning (RIC) transplants will hasten T cell reconstitution without adversely impacting clinical outcomes. This idea is being tested in a randomized phase 2 clinical trial comparing GVHD prophylaxis using a regimen of tacrolimus & MMF 15 mg/kg q 12 h for 30 days in the control (MMF30) vs. 15 days in the study cohort (MMF15). The MMF15 patients received GM-CSF to promote early monocyte recovery; MMF 30 got G-CSF. All patients underwent reduced intensity conditioning with ATG 1.7 mg/kg/d given on days -9 thru -7 & 450 cGy total body irradiation on d-1 & 0. Patients were stratified based on diagnosis and donor type (8/8 or 7/8 HLA MRD or MUD). A response-adaptive randomization scheme was used to increase the probability that patients were allocated to the treatment regimen which yields superior donor-derived CD3+ (ddCD3) cell count by 8 weeks; primary endpoint is relapse free, DLI free survival. Preliminary results from the first 21 evaluable patients are presented. Patients baseline characteristics are summarized in table 1. Mean ddCD3 count at 8 weeks post HCT favored the MMF group (461 vs. 329), which led to more patients allocated to MMF15 cohort. Median myeloid engraftment at day 60 was 100% in both cohorts. Mean absolute lymphocyte count, CD3+ and CD4+ T-cell counts were higher in the MMF15 cohort on day 30 (500 vs 200/mL−1, P=0.005; 254 vs. 71/mL−1, P=0.0188; 107 vs. 25/mL−1, P=0.0036 respectively). There was a trend for higher ddCD3 cell count in the MMF15 cohort (Fig. 1). Despite this there were no significant differences noted on in lymphoid recovery at later time points. Despite a shorter course of MMF there was no significant difference in the rates of acute and chronic GVHD, relapse and patient survival between the two cohorts (Fig 2). In conclusion these early data demonstrate that a shorter 15-day course of MMF plus GM-CSF led to rapid, early T cell reconstitution post HCT without a significant increase in the risk of acute or chronic GVHD, or disease relapse. This effect is consistent with immune reconstitution post HCT being a dynamical rather than a stochastic process, which may be modified in real-time by adjustments in the intensity of GVHD prophylaxis.

Effects of tacrolimus (FK506) and mycophenolate mofetil (MMF) on regulatory T cells and co-inhibitory receptors in the peripheral blood of human liver allograft patients

Context: Recent studies have shown that a combination treatment of mycophenolate mofetil (MMF) and tacrolimus (FK506) may be an option for organ transplantation patients.Objective: In this study, we detected the effects of FK506 and MMF on the expressions of regulatory T cells (Tregs) and co-inhibitory receptors on Tregs in peripheral blood mononuclear cells (PBMC) of patients with stable phase after liver transplantation.Materials and methods: A total of 35 patients with stable stage after 6 months of liver transplantation were divided into two groups including 20 patients were treated with FK506 monotherapy (FK506 group), and 15 patients with FK506 and MMF combination (FK506 + MMF group). 15 healthy subjects were served as the control.Results: It is found that percentages of CD3+, CD3+CD4+ and CD3+CD8+ T cells in FK506 group are lowered compared to the control group but they are elevated in FK506 + MMF group. Amount of CD4+CD25+CD127low/-Treg cells in CD3+ CD4+T cells in FK506 + MMF group was higher than that in FK506 group and control group. The expressions of co-inhibitory receptors (CTLA-4, PD-1, Tim-3, LAG-3 and TIGIT) on Tregs in FK506 + MMF group were significant higher than those in the FK506 group and control group. The levels of the relative cytokines (TGF-β and IL-10) in FK506 group are down-regulated compared to the control group.Conclusion: The application of FK506 combined with MMF may be superior to FK506 monotherapy for the patients to further induce the immune tolerance after liver transplantation.

Mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA-associated vasculitis: a randomised, non-inferiority trial

ObjectivesCyclophosphamide induction regimens are effective for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but are associated with infections, malignancies and infertility. Mycophenolate mofetil (MMF) has shown high remission rates in small...

Outcomes of Cadaveric Renal Transplantation Using Mycophenolate Mofetil or Azathioprine in South Africa

Abstract Introduction: Mycophenolate mofetil (MMF) has, to a great extent, replaced azathioprine (AZA) in immunosuppressive regimens worldwide in the prevention of acute allograft rejection. However, there are no studies in South Africa to show that MMF is superior to AZA. Objectives: To describe the outcomes of cadaveric renal transplantation in patients treated with either MMF or AZA and followed up over a 5-year period. Design: This was a retrospective comparative study. Methods: A convenience sample of all eligible patients, 208 in total, was recruited from the Renal Transplant Unit at the Charlotte Maxeke Johannesburg Academic Hospital from 1985 to 2013, who were treated with either MMF or AZA. Results: Of the 208 patients, 101 patients were treated with AZA and 107 patients treated with MMF, in addition to corticosteroids and cyclosporine. A total of 16 patients developed acute allograft rejection 12–52 weeks after cadaveric transplantation. Of these, 6% were in the AZA group and 10% in the MMF group. There was a 1% mortality in the MMF group and 16.8% in the AZA group (p &lt; 0.001). The serum creatinine at a 3-month follow-up was found to be a strong predictor of allograft function in patients on MMF (p &lt; 0.001). Conclusion: Patient survival was superior in the long term in cadaveric renal transplant patients receiving MMF therapy.

The Effect of Mycophenolate Mofetil on Non-Renal Manifestations in Systemic Lupus Erythematosus: Results from Korean Lupus Network Registry.

BackgroundThe objective of this study was to identify the effects of mycophenolate mofetil (MMF) on non-renal manifestations in systemic lupus erythematosus (SLE).MethodsThe study population comprised 439 SLE patients from the Korean Lupus Network registry who were followed up annually and completed the baseline survey and two follow-up visits from 2014 to 2018. Disease activity, laboratory markers, and clinical manifestations including mucocutaneous lesions, arthritis, serositis, neurological disorders, and hematologic/immunologic abnormalities were assessed. All variables by group (MMF and non-MMF) effects with time (baseline, 1st follow-up, and 2nd follow-up) were analyzed by generalized estimation equation.ResultsSeventy-two patients were treated with MMF. There was significant difference in frequencies of malar rash, arthritis, renal disorder, and hematologic disorder between MMF and non-MMF groups in total SLE patients. In subgroup analysis of hematologic abnormalities in total patients, frequency of leukopenia was significantly different between the two groups during follow-up (P = 0.001), but frequencies of hemolytic anemia, lymphopenia, and thrombocytopenia were not. In addition, frequencies of leukopenia in patients without lupus nephritis were significantly decreased in MMF group compared to non-MMF group (P = 0.012).ConclusionThis study showed that MMF might be a beneficial treatment for hematologic abnormalities, especially leukopenia, in SLE.

Mycophenolate mofetil for maintenance of remission in children with steroid- and calcineurin inhibitor- dependent nephrotic syndrome: A prospective, randomized multicenter trial

Background: Mycophenolate mofetil (MMF), a nonsteroidal immunosuppressive agent, has been used as a therapeutic option in various immune-mediated glomerulonephritis. However, controlled studies that examine the efficacy of MMF monotherapy in steroid- and calcineurin inhibitor (CNI)-dependent nephrotic syndrome (NS) are lacking. Aim: This study assessed the efficacy and safety of MMF monotherapy in children with steroid- and CNI-dependent NS. Methods: In this prospective, randomized, open-label, multicenter pilot study, we evaluated the efficacy and safety of MMF after CNI and corticosteroid therapy in children with steroid-dependent NS. We compared the duration and timing of sustained remission between patients managed with or without MMF and monitored for adverse effects of MMF. Statistical Analysis Used: The data were analyzed using standard statistical tests on the modified intention-to-treat population. Results: The baseline characteristics between the two groups did not differ significantly. There was neither difference in the duration of the sustained remission between patients in the MMF and control groups (4.2 ± 3.5 months vs. 3.8 ± 3.4 months, respectively; P = 0.772) nor in the proportion in sustained remission after 12 months (P = 0.936). Patients received MMF did not experience significant toxicity; chiefly, self-remitting gastrointestinal adverse events were observed. Conclusions: Therapy with MMF is safe but ineffective in influencing rates of remission in patients with NS dependent on steroids and CNIs.

Analysis of different treatments and their outcomes in idiopathic membranous nephropathy: a single-center observational study

Background Although there are multiple treatment modalities for idiopathic membranous nephropathy (IMN) which have been studied in different streams of populations, there is no single convincing answer for the best accepted modality. In the study presented, we have made an effort to compare the different treatment regimens and analyze the results obtained. Patients and methods This was a retrospective observational study. A total number of 54 patients with idiopathic membranous nephropathy were included in the study. Five different treatment groups were made, which included modified Ponticelli regime, oral cyclophosphamide, oral mycophenolate mofetil, oral tacrolimus, and intravenous rituximab therapy, and were followed up for 1 year. Urine protein to creatinine ratio, serum albumin, creatinine, and estimated glomerular filtration rate were noted at 1, 3, 6, 9, and 12 months. Results Among the 54 patients, 10 of 16 patients in modified Ponticelli group, 9 of 18 in oral cyclophosphamide group, 4 of 9 in oral mycophenolate mofetil group, 3 of 6 in oral tacrolimus group, and 3 of 5 in intravenous rituximab group achieved remission. There was statistically significant improvement in renal function in modified Ponticelli group (P=0.02) and oral cyclophosphamide group (P=0.01) as compared with the other groups. Conclusion Patients who received modified Ponticelli regime had superior outcomes in terms of improvement in renal function and renal survival as compared with other different therapies. Large studies with long-term follow ups are needed to support the outcome.

Comparative Study of Mycophenolate Mofetil and Methotrexate in Graft-Versus-Host Disease Prophylaxis in Adult Recipients of Related and Unrelated Allo-HSCT

Background. Although the use of methotrexate (MTX) and mycophenolate mofetil (MMF) for prophylaxis of graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) was compared in a large number of studies, the published results are contradictory. This fact provides ground for the present retrospective single-center trial comparing these two approaches in GVHD prophylaxis. Materials &amp; Methods. The present study included 294 allo-HSC recipients with MTX prophylaxis and 172 allo-HSC recipients with MMF prophylaxis. 36 % of patients underwent matched related donor transplantation, and 64 % of patients received matched unrelated donor transplantation. Results. Univariate and multivariate analyses showed that probability of acute grade 2-4 GVHD was 36 % vs. 39 % (hazard ratio [HR] 1.297; 95% confidence interval [95% CI] 0.931-1.795; p = 0.122), grade 3-4 GVHD was 21 % vs. 25 % (HR 1.472; 95% CI 0.951-2.256; p = 0.05), and probability of chronic GVHD was 52 % vs. 55 % (HR 0.978; 95% CI 0.951-1.406; p = 0.91). In the MTX and MMF groups there were no significant differences in transplantation mortality (HR 1.173; 95% CI 0.797-1.708; p = 0.43), relapse incidence (HR 1.034; 95% CI 0.743-1.428; p = 0.84), overall survival (HR 1.087; 95% CI 0.825-1.433; p = 0.55), event-free survival (HR 1.108; 95% CI 0.854-1.437; p = 0.43), disease and GVHD free survival (HR 1.065; 95% CI 0.845-1.343; p = 0.59). Engraftment occurred earlier when MMF was used (p = 0.035). Administration of MMF instead of MTX was associated with lower probability of grade 3-4 toxic hepatitis (7 % vs. 31 %; p &lt; 0.0001) and grade 3-4 mucositis (23 % vs. 45 %; p = 0.0002). Conclusion. The efficacy of GVHD prophylaxis using MMF is comparable with that of MTX, but MMF is associated with a better safety profile due to reduced incidence of severe liver toxicity and mucositis.

Mycophenolate mofetil versus cyclophosphamide for idiopathic membranous nephropathy; a double blind and randomized clinical trial

Introduction: The current treatment regimens for patients with idiopathic membranous nephropathy (MN) are based on cyclophosphamide-glucocorticoid or calcineurin inhibitor-glucocorticoid. Objectives: We evaluated whether mycophenolate mofetil (MMF) -glucocorticoid could be an option for first-line therapy among these patients. Patients and Methods: In a double-blinded, randomized and controlled clinical trial, we compared the effect of MMF with cyclophosphamide in inducing complete or partial remission (PR) among patients with nephrotic syndrome due to idiopathic MN. All of the patients in both groups also received steroid, renin-angiotensin blockers and statins. Diuretics were also used in the patients who had edema. The primary end point of our study was change in urinary protein/creatinine ratio. Results: A total of 30 patients completed the study. Around 17 patients received MMF (2 g/d) and 13 patients received intravenous or oral cyclophosphamide for 6 months. At the start of the study, no significant differences in demographic and biochemical parameters of patients including the urinary protein excretion rate between two groups (P = 0.432). The proportion of proteinuria was 5235 ± 1655 mg/24 in MMF group and 8781 ± 8741 mg/24 in the cyclophosphamide group at the beginning of the study. The rate of complete and PR were 5.9% and 52.9 in MMF group versus 16.7% and 100% in cyclophosphamide group which it is significantly lower in MMF group. Kidney function was stable in both groups during treatment. Conclusions: According to the result of our study, a 6-month therapy with MMF-glucocorticoid is not recommended for treatment of patients with nephrotic syndrome due to idiopathic MN.

Longitudinal Changes in Quantitative Interstitial Lung Disease on Computed Tomography after Immunosuppression in the Scleroderma Lung Study II.

The Scleroderma Lung Study II (SLS II) demonstrated significant improvements in pulmonary function and dyspnea at 24 months compared with baseline when patients with symptomatic scleroderma-related interstitial lung disease (SSc-ILD) were treated with either cyclophosphamide for 1 year (followed for another year on placebo) or mycophenolate mofetil for 2 years in a randomized, double-blind clinical trial. Physiologic and clinical outcomes of SLS II have been published previously. The aim of the study was to assess changes from baseline in the extent of SSc-ILD on high-resolution computed tomography (HRCT) measured in the SLS II participants using quantitative image analysis after 2 years and to determine whether these HRCT changes were correlated with the changes in physiologic and clinical measures over the same time interval. Ninety-seven of the 142 randomized subjects (cyclophosphamide group, 47 subjects; mycophenolate mofetil group, 50 subjects) participating in SLS II underwent thoracic volumetric thin-section HRCT at both baseline and 24 months. Quantitative computer-aided diagnosis scores using volumetric HRCT scans were obtained using a previously developed computer-aided system. The scores were quantitative lung fibrosis, quantitative ground glass, quantitative honeycomb, and quantitative interstitial lung disease (QILD), the latter representing the sum of quantitative lung fibrosis, quantitative ground glass, and quantitative honeycomb. These scores were obtained both for the whole lung and for individual lobes. Paired t tests were used for the combined (pooled) cyclophosphamide and mycophenolate mofetil groups to compare 24-month changes from baseline in both the whole lung and the lobe of maximal involvement as determined at baseline (worst lobe). At the end of the 24-month trial, QILD in the whole lung was significantly reduced by a mean of 2.51% in the pooled groups (adjusted 95% confidence interval, -4.00 to -1.03%; P = 0.001). There was no significant difference in the QILD score improvement between the cyclophosphamide (-2.66%) and mycophenolate (-2.38%) groups when assessed separately (P = 0.88). For the pooled group, the 24-month changes in QILD scores in the whole lung correlated significantly with other outcomes, including 24-month changes in forced vital capacity (ρ = -0.37), single-breath diffusing capacity of the lung for carbon monoxide (ρ = -0.22), and breathlessness as measured by the Transition Dyspnea Index (ρ = -0.26). Treatment of SSc-ILD with either cyclophosphamide for 1 year, followed by placebo for a second year, or mycophenolate for 2 years was associated with a significant reduction (improvement) in the extent of HRCT SSc-ILD assessed by computer-aided diagnosis scores, which correlated well with one or more other measures of treatment response. These findings demonstrate that actual changes in lung structure accompany improvements in physiologic and/or symptomatic measures in SSc-ILD.

Comparison of Sirolimus Combined With Tacrolimus and Mycophenolate Mofetil Combined With Tacrolimus in Kidney Transplantation Recipients: A Meta-Analysis

PurposeThe study was designed to compare the outcomes of sirolimus (SRL) combined with tacrolimus (TAC) and mycophenolate mofetil (MMF) combined with TAC in kidney transplantation recipients. MethodsA literature search of PubMed, Embase, and Web of Science was performed to identify relevant studies, and the last update was on February 1, 2018. All studies with appropriate data comparing the SRL group with the MMF group were included. SRL and MMF were used in sufficient doses. Relevant information was recorded and analyzed. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the effects of SRL and MMF. Relevant outcomes, including delayed graft function, acute rejection, graft survival, seroma, anemia, lymphocele, and hyperlipidemia, were compared. ResultsTen studies with a total of 2357 patients (n = 1256 receiving SRL vs n = 1101 receiving MMF) were ultimately included. Our results indicated that the SRL group experienced a higher rate of hyperlipidemia (OR: 1.864; 95% CI, 1.494–2.325) and lymphocele (OR: 2.58; 95% CI, 1.49–4.47). However, no significant differences were detected regarding the rates of delayed graft function, acute rejection, graft survival, infectious complications, anemia, or seroma. ConclusionsThis meta-analysis suggested that SRL combined with TAC and MMF combined with TAC were equally safe and effective for the kidney transplantation recipients. However, the MMF group exhibited a marginally significant advantage of lower incidence of hyperlipidemia and lymphocele.