Mofetil Combination Research Articles

Evaluation of neutropenia secondary to mycophenolate mofetil associated with valganciclovir in liver transplant patients

ObjectiveImmunosuppressive drugs are necessary to avoid or reduce the risk of rejection of transplanted organs. The immunosuppression generated may result in these patients needing antibiotics and antivirals to be prescribed to them in conjunction with their immunosuppressants to avoid the risk of infection. This has generated an increase in neutropenia in patients treated with mycophenolate mofetil in combination with valganciclovir. The purpose of this study is to estimate the risk of neutropenia attributable to combination treatment of mycophenolate mofetil with valganciclovir in patients with a transplanted liver. MethodThis is a retrospective cohort study. It included patients who received a liver transplant between 2012 and 2017 and who were treated with mycophenolate mofetil or with a combination of mycophenolate mofetil and valganciclovir. Minimum follow-up was 100 days post-transplantation. Children under 16 years of age and patients who died during follow-up were excluded. Binary logistic regression analysis was used to determine the association of neutropenia with sex, age, diabetes, creatinine at baseline and at discharge, and concomitant treatment of mycophenolate mofetil with valganciclovir. Relative risk and 95% CI were calculated using logistic regression coefficients. Results144 patients were analyzed, 87 were treated with mycophenolate mofetil and 57 received mycophenolate mofetil and valganciclovir together. An overall risk of neutropenia of 37% [95% CI (29-45)] was observed. The risk was significantly higher in patients who received the combination of mycophenolate mofetil and valganciclovir (56%) than in those treated with mycophenolate mofetil alone (24%), p = 0.001. Binary-logistic-regression analysis revealed that concomitant use of mycophenolate mofetil with valganciclovir was associated with an increased risk of neutropenia: Relative risk = 4.97, 95% CI [2.25-11.00]. ConclusionsOur study shows that concomitant use of mycophenolate mofetil and valganciclovir increases the risk of neutropenia in patients with a transplanted liver.

Impact of everolimus versus mycophenolate mofetil in combination with reduced tacrolimus on oncologic outcome after liver transplantation for hepatocellular carcinoma

Impact of everolimus versus mycophenolate mofetil in combination with reduced tacrolimus on oncologic outcome after liver transplantation for hepatocellular carcinoma

Impact of everolimus versus mycophenolate mofetil in combination with reduced tacrolimus in liver transplantation patients with hepatocellular carcinoma within Milan criteria

Impact of everolimus versus mycophenolate mofetil in combination with reduced tacrolimus in liver transplantation patients with hepatocellular carcinoma within Milan criteria

Antibody Response to SARS-CoV-2 mRNA Vaccine Among Kidney Transplant Recipients: A Retrospective Cohort Study at a Single Transplant Institute in Japan.

Although the effectiveness of vaccines in protecting the host from infection has been proven, few surveys have been conducted on changes in antibody levels after vaccination of kidney transplant recipients in Japan. We analyzed serological responses in kidney transplant recipients after BNT162B2 COVID-19 mRNA vaccine with the use of a reagent capable of simultaneously specifying the antibody response to 5 proteins: a full-spike protein (extracellular domain), 3 individual domains of the spike protein (S1, S2, and receptor-binding domain), and nucleocapsid. The analysis involved 111 patients who had follow-up over 1 month after having received the second of 2 coronavirus vaccines after kidney transplant. Antibodies were detected in 46 of 111 patients (41%). The antibody-positive rate in the kidney transplant group tended to be lower than that in the healthy control group, which showed an antibody- positive rate of 100%. When the antibody-positive rate was analyzed by the type of immunosuppressor used, the rate was 36% (37/100) for patients who used tacrolimus at the time of vaccination and 90% (9/10) for patients who used cyclosporine. Patients administered CD20 antibody (rituximab) before and/or after transplant showed a lower production of antibodies, which was supported by a smaller number of CD19- and CD20-positive cells in the peripheral blood as well as a shorter period between rituximab administration and vaccination. The percentage of responding viral fragments varied greatly among individual patients and showed no uniformity in the kidney transplant group, whereas the mean fluorescence intensity of individual fragments showed a certain tendency in the control group. The appropriate timing of vaccination should be considered in transplant recipients who use tacrolimus-mycophenolate mofetil combination and rituximab as these drugs are deeply related to a lower antibody response to SARS-CoV-2 BNT162b2 vaccination.

Humoral responses after second and third SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders on immunosuppressants: a cohort study

BackgroundDisease-specific studies have reported impaired humoral responses after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders treated with specific immunosuppressants. Disease-overarching studies, and data on recall responses and third vaccinations are scarce. Our primary objective was to investigate the effects of immunosuppressive monotherapies on the humoral immune response after SARS-CoV-2 vaccination in patients with prevalent immune-mediated inflammatory disorders.MethodsWe did a cohort study in participants treated in outpatient clinics in seven university hospitals and one rheumatology treatment centre in the Netherlands as well as participants included in two national cohort studies on COVID-19-related disease severity. We included patients aged older than 18 years, diagnosed with any of the prespecified immune-mediated inflammatory disorders, who were able to understand and complete questionnaires in Dutch. Participants with immune-mediated inflammatory disorders who were not on systemic immunosuppressants and healthy participants were included as controls. Anti-receptor binding domain IgG responses and neutralisation capacity were monitored following standard vaccination regimens and a three-vaccination regimen in subgroups. Hybrid immune responses—ie, vaccination after previous SARS-CoV-2 infection—were studied as a proxy for recall responses.FindingsBetween Feb 2 and Aug 1, 2021, we included 3222 participants in our cohort. Sera from 2339 participants, 1869 without and 470 participants with previous SARS-CoV-2 infection were analysed (mean age 49·9 years [SD 13·7]; 1470 [62·8%] females and 869 [37·2%] males). Humoral responses did not differ between disorders. Anti-CD20 therapy, sphingosine 1-phosphate receptor (S1P) modulators, and mycophenolate mofetil combined with corticosteroids were associated with lower relative risks for reaching seroconversion following standard vaccination (0·32 [95% CI 0·19–0·49] for anti-CD20 therapy, 0·35 [0·21–0·55] for S1P modulators, and 0·61 [0·40–0·90] for mycophenolate mofetil combined with corticosteroids). A third vaccination increased seroconversion for mycophenolate mofetil combination treatments (from 52·6% after the second vaccination to 89·5% after the third) but not significantly for anti-CD20 therapies (from 36·8% to 45·6%) and S1P modulators (from 35·5% to 48·4%). Most other immunosuppressant groups showed moderately reduced antibody titres after standard vaccination that did not increase after a third vaccination, although seroconversion rates and neutralisation capacity were unaffected. In participants with previous SARS-CoV-2 infection, SARS-CoV-2 antibodies were boosted after vaccination, regardless of immunosuppressive treatment.InterpretationHumoral responses following vaccination are impaired by specific immunosuppressants. After standard vaccination regimens, patients with immune-mediated inflammatory disorders taking most immunosuppressants show similar seroconversion to controls, although antibody titres might be moderately reduced. As neutralisation capacity and recall responses are also preserved in these patients, this is not likely to translate to loss of (short-term) protection. In patients on immunosuppressants showing poor humoral responses after standard vaccination regimens, a third vaccination resulted in additional seroconversion in patients taking mycophenolate mofetil combination treatments, whereas the effect of a third vaccination in patients on anti-CD20 therapy and S1P modulators was limited.FundingZonMw (The Netherlands Organization for Health Research and Development).

British Association of Dermatologists guidelines for the management of people with cutaneous lupus erythematosus 2021.

The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of cutaneous lupus erythematosus (CLE) in the presence or absence of systemic lupus erythematosus (SLE) in adults, young people and children. The document aims to: offer an appraisal of all relevant literature up to December 2020, focusing on any key developments address important, practical clinical questions relating to the primary guideline objective. provide guideline recommendations and if appropriate research recommendations.

Management of Cardiac Sarcoidosis Using Mycophenolate Mofetil as a Steroid-Sparing Agent

BackgroundCardiac sarcoidosis (CS) is a major cause of morbidity and mortality in patients with systemic sarcoidosis. Steroid-sparing agents are increasingly used, despite a lack of randomized trials or published guidelines to direct treatment. Methods and ResultsThis retrospective study included 77 patients with CS treated with prednisone monotherapy (n = 32) or a combination with mycophenolate mofetil (n = 45) between 2003 and 2018. Baseline characteristics and clinical outcomes were evaluated. The mean patient age was 53 ± 11 years at CS diagnosis, 66.2% were male, and 35.1% were Black. The total exposure to maximum prednisone dose (initial prednisone dose × days at dose) was lower in the combination therapy group (1440 mg [interquartile range (IQR), 1200–2760 mg] vs 2710 mg [IQR, 1200–5080 mg]; P = .06). On 18F-fluorodeoxyglucose positron emission tomography scans, both groups demonstrated a significant decrease in the cardiac maximum standardized uptake value after treatment: a median decrease of 3.9 (IQR 2.7–9.0, P = .002) and 2.9 (IQR 0–5.0, P = .001) for prednisone monotherapy and combination therapy, respectively. Most patients experienced improvement or complete resolution in qualitative cardiac 18F-fluorodeoxyglucose uptake (92.3% and 70.4% for the prednisone and combination therapy groups, respectively). Mycophenolate mofetil was well tolerated. ConclusionsMycophenolate mofetil in combination with prednisone for the treatment of CS may minimize corticosteroid exposure and decrease cardiac inflammation without significant adverse effects.

Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Governs GVHD and Immunosuppression Need, Reducing Late Toxicities in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors.

Combined direct antineoplastic activity and the long-lasting immunological effects of allogeneic hematopoietic cell transplant (HCT) can cure many hematological malignancies, but broad adoption requires non-relapse mortality (NRM) rates and graft-versus-host disease (GVHD) control. Recently, posttransplant cyclophosphamide (PTCy) given after a bone marrow transplant significantly reduced GVHD-incidence, while PTCy given with tacrolimus/mofetil mycophenolate (T/MMF) showed activity following allogeneic peripheral blood stem cell transplantation (alloPBSCT). Here, we report the experience of a larger cohort (85 consecutive patients) and expanded follow-up period (03/2011–12/2019) with high-risk hematological malignancies who received alloPBSCT from Human-Leukocyte-Antigens HLA-matched unrelated/related donors. GVHD-prophylaxis was PTCy 50 mg/kg (days+3 and +4) combined with T/MMF (day+5 forward). All patients stopped MMF on day+28 with day+110 = median tacrolimus discontinuation. Cumulative incidences were 12% for acute and 7% for chronic GVHD- and no GVHD-attributed deaths. For surviving patients, the 12, 24, and 36-month probabilities of being off immunosuppression were 92, 96, and 96%, respectively. After a 36-month median follow-up, NRM was 4%; median event-free survival (EFS) and overall survival (OS) had yet to occur. One- and two-year chronic GVHD-EFS results were 57% (95% CI, 46–68%) and 53% (95% CI, 45–61%), respectively, with limited late infections and long-term organ toxicities. Disease relapse caused the most treatment failures (38% at 2 years), but low transplant toxicity allowed many patients (14/37, 38%) to receive donor lymphocyte infusions as a post-relapse strategy. We confirmed that PTCy+T/MMF treatment effectively prevented acute and chronic GVHD and limited NRM to unprecedented low rates without loss of disease control efficacy in an expanded patient cohort. This trial is registered at U.S. National Library of Medicine as #NCT02300571.

Immunosuppression Has Long-Lasting Effects on Circulating Follicular Regulatory T Cells in Kidney Transplant Recipients.

Background: FoxP3+ follicular regulatory T cells (Tfr) have been identified as the cell population controlling T follicular helper (Tfh) cells and B cells which, are both involved in effector immune responses against transplanted tissue.Methods: To understand the biology of Tfr cells in kidney transplant patients treated with tacrolimus and mycophenolate mofetil (MMF) combination immunosuppression, we measured circulating (c)Tfh and cTfr cells in peripheral blood by flow cytometry in n = 211 kidney transplant recipients. At the time of measurement patients were 5–7 years after transplantation. Of this cohort of patients, 23.2% (49/211) had been previously treated for rejection. Median time after anti-rejection therapy was 4.9 years (range 0.4–7 years). Age and gender matched healthy individuals served as controls.Results: While the absolute numbers of cTfh cells were comparable between kidney transplant recipients and healthy controls, the numbers of cTfr cells were 46% lower in immunosuppressed recipients (p < 0.001). More importantly, in transplanted patients, the ratio of cTfr to cTfh was decreased (median; 0.10 vs. 0.06), indicating a disruption of the balance between cTfr and cTfh cells. This shifted balance was observed for both non-rejectors and rejectors. Previous pulse methylprednisolone or combined pulse methylprednisolone + intravenous immunoglobulin anti-rejection therapy led to a non-significant 30.6% (median) and 51.2% (median) drop in cTfr cells, respectively when compared to cTfr cell numbers in transplant patients who did not receive anti-rejection therapy. A history of alemtuzumab therapy did lead to a significant decrease in cTfr cells of 85.8% (median) compared with patients not treated with anti-rejection therapy (p < 0.0001). No association with tacrolimus or MMF pre-dose concentrations was found.Conclusion: This cross-sectional study reveals that anti-rejection therapy with alemtuzumab significantly lowers the number of cTfr cells in kidney transplant recipients. The observed profound effects by these agents might dysregulate cTfr functions.

Tacrolimus Monotherapy in Recipients of Liver Transplant: A Single-Center Experience

IntroductionFollowing liver transplantation (LT), the majority of patients are treated with reduced-dose calcineurin inhibitors (CNIs) in combination with mycophenolate mofetil. The optimal timing for subsequent conversion to CNI monotherapy is not clearly defined. This study aims to evaluate the safety of conversion to CNI monotherapy after LT. MethodsThis was a single-center retrospective study of 100 consecutive patients who received CNI and mycophenolate mofetil combination regimen after LT at Singapore General Hospital from 2006 to 2018. Patient demographics, clinical parameters, and posttransplant complications (ie, rates of graft rejection, de novo malignancy, cytomegalovirus infection and renal impairment) were recorded. ResultsOne hundred patients were recruited and mean follow-up time in months ± standard deviation was 60.36 ± 41.73. Patients were divided into 2 groups based on institution of CNI monotherapy within (group 1) or beyond (group 2) 6 months. Twenty-five (25%) patients were on CNI monotherapy within 6 months post-LT. Overall patient survival was 83.7% at 5-years posttransplant. There was no statistical difference in the rates of posttransplant complications including liver graft rejection (4.0% vs 18.7%, P = .11); de novo malignancy (0.0% vs 8.0%, P = .33); cytomegalovirus infection (4.0% vs 1.3%, P = .44); and renal impairment (20.0% vs 40.0%, P = .069) between the 2 groups. ConclusionsSuccessful institution of CNI monotherapy within 6 months is safe, and does not increase the risk of rejection.

Population Pharmacokinetics of Voriconazole in Chinese Patients with Hematopoietic Stem Cell Transplantation.

Voriconazole is widely recommended for the prevention and treatment of invasive fungal infections in hematopoietic stem cell transplantation patients. However, its use is limited by a narrow therapeutic range and large inter-individual variability. This study aimed to characterize the pharmacokinetics of voriconazole in Chinese hematopoietic stem cell transplantation patients, to explore factors affecting its pharmacokinetic parameters, and to provide recommendations for its optimal dosing regimens. A total of 121 serum concentration samples from 23 patients were retrospectively included. Voriconazole concentrations were detected, and patient clinical data were recorded. Population pharmacokinetic analysis was performed by a non-linear, mixed-effect modeling approach. Goodness-of-fit plots, bootstrap method, prediction-corrected visual predictive check and external validation by an independent group of seven patients were performed to evaluate the final model. A one-compartment model with first-order elimination successfully described the data. The absorption rate constant was fixed at 1.1h-1 and bioavailability was fixed at 0.895. The typical values for voriconazole clearance and distribution volume were 9.52 L/h and 155 L, respectively. CYP2C19*2 genotype and mycophenolate mofetil combination presented a significant impact on the clearance. Compared with CYP2C19*2 carriers, voriconazole clearance was proven to be higher in CYP2C19*1/*1 patients. A population pharmacokinetic model of voriconazole was successfully established in Chinese hematopoietic stem cell transplantation patients. Based on the final model, CYP2C19*2 genotyping coupled with therapeutic drug monitoring seems to be useful to guide voriconazole dosing and to explain subtherapeutic concentrations in clinical practice.

Azathioprine Versus Mycophenolate Mofetil in Combination with Tacrolimus and Steroids Maintenance in Pediatric Kidney Transplantation

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Nine years old child with nephrotic syndrome: a case of biopsy proven lupus nephritis in tertiary level medical college hospital in Mymensingh, Bangladesh

We observed a case of a 9 years old female patient who presented with nephrotic syndrome and impaired renal function diagnosed to have Systemic Lupus Erythematosus (SLE). Lupus nephritis (LN) is a common major organ manifestation of SLE and causes significantly increased morbidity and mortality. Thus, all patients with SLE should be regularly screened for LN. This patient presented with nephrotic syndrome, pleural effusion and pericardial effusion which depicts the multisystem effects of SLE. This patient was treated with Oral Mycophenolate Mofetilin combination with steroid as induction therapy and attained remission after a month of treatment. Systemic lupus erythematosus should be considered in patients with nephrotic syndrome and these patients should have renal biopsy to determine renal involvement.&#x0D; CBMJ 2018 January: Vol. 07 No. 01 P: 40-44

Mycophenolate Mofetil in Combination with Steroids for Treatment of C3 Glomerulopathy: A Case Series.

C3 glomerulopathy is a form of complement-mediated GN. Immunosuppressive therapy may be beneficial in the treatment of C3 glomerulopathy. Mycophenolate mofetil is an attractive treatment option given its role in the treatment of other complement-mediated diseases and the results of the Spanish Group for the Study of Glomerular Diseases C3 Study. Here, we study the outcomes of patients with C3 glomerulopathy treated with steroids and mycophenolate mofetil. We conducted a retrospective chart review of patients in the C3 glomerulopathy registry at Columbia University and identified patients treated with mycophenolate mofetil for at least 3 months and follow-up for at least 1 year. We studied clinical, histologic, and genetic data for the whole group and compared data for those who achieved complete or partial remission (responders) with those who did not achieve remission (nonresponders). We compared remission with mycophenolate mofetil with remission with other immunosuppressive regimens. We identified 30 patients who met inclusion criteria. Median age was 25 years old (interquartile range, 18-36), median creatinine was 1.07 mg/dl (interquartile range, 0.79-1.69), and median proteinuria was 3200 mg/g creatinine (interquartile range, 1720-6759). The median follow-up time was 32 months (interquartile range, 21-68). Twenty (67%) patients were classified as responders. There were no significant differences in baseline characteristics between responders and nonresponders, although initial proteinuria was lower (median 2468 mg/g creatinine) in responders compared with nonresponders (median 5000 mg/g creatinine) and soluble membrane attack complex levels were higher in responders compared with nonresponders. For those tapered off mycophenolate mofetil, relapse rate was 50%. Genome-wide analysis on complement genes was done, and in 12 patients, we found 18 variants predicted to be damaging. None of these variants were previously reported to be pathogenic. Mycophenolate mofetil with steroids outperformed other immunosuppressive regimens. Among patients who tolerated mycophenolate mofetil, combination therapy with steroids induced remission in 67% of this cohort. Heavier proteinuria at the start of therapy and lower soluble membrane attack complex levels were associated with treatment resistance.

State-of-the-art immunosuppression protocols for pediatric renal transplant recipients.

Immunosuppressive protocols used in pediatric kidney transplantation have changed substantially within the last decade. Many transplant centers now focus on the use of tacrolimus and mycophenolate mofetil in combination with early steroid withdrawal, frequently combined with antibody induction therapy. However, this approach is mainly based on treatment efficacy and-compared to other immunosuppressive regimens used in this context-leads to higher rates of viral infections in patients. In this review I assess data from prospective, interventional trials of immunosuppressive therapy in pediatric kidney transplantation. However, since there is a paucity of randomized controlled trials, I also describe the results of studies with weaker designs. The advantages and disadvantages of different immunosuppressive strategies are discussed. Within this framework I suggest ideas for individualized immunosuppressive regimens based on different stratificators that could effect a change from a 'one size fits all' to a tailored approach for initial and maintenance immunosuppressive therapy after renal transplantation in the pediatric setting.

GvHD prophylaxis after single-unit reduced intensity conditioning cord blood transplantation in adults with acute leukemia.

To investigate better GVHD prophylaxis in reduced intensity conditioning umbilical cord blood transplantation (RIC-UCBT), we compared transplant outcomes after UCBT among GvHD prophylaxes using the registry data. We selected patients transplanted for AML or ALL with a calcineurin inhibitor and methotrexate (MTX)/mycophenolate mofetil (MMF) combination. A total of 748 first RIC-UCBT between 2000 and 2012 (MTX+ group, 446, MMF+ group, 302) were included. The cumulative incidence of neutrophil and platelet counts higher than 50 000/μL was significantly better in the MMF+ group (relative risk (RR), 1.55; P<0.001: RR, 1.34; P=0.003, respectively). In multivariate analyses, the risk of grade II-IV and III-IV acute GvHD was significantly higher in the MMF+ group than in the MTX+ group (RR, 1.75; P<0.001: RR, 1.97; P=0.004, respectively). In disease-specific analyses of AML, the risk of relapse of high-risk disease was significantly lower in the MMF+ group (RR, 0.69; P=0.009), whereas no significant difference was observed in the risk of relapse-free and overall survival in high-risk disease. In patients with standard-risk disease, no significant differences were noted in the risk of relapse or survival between the MTX+ and MMF+ groups. Collectively, these results suggest that MMF-containing prophylaxis may be preferable in RIC-UCBT, particularly for high-risk disease.

Refractory optic perineuritis due to granulomatosis with polyangiitis successfully treated with methotrexate and mycophenolate mofetil combination therapy.

Optic perineuritis is an uncommon inflammatory disorder of the optic sheath that causes visual loss or eye pain. There are few case reports of optic perineuritis associated with granulomatosis with polyangiitis. Herein we report the case of a 37-year-old male with granulomatosis with polyangiitis and who presented with headache, blurred vision in the right eye, diplopia, and numbness in the right forehead. Brain magnetic resonance images (MRI) findings revealed hypertrophic pachymeningitis and refractory optic perineuritis. These were manageable only by means of weekly methotrexate and mycophenolate mofetil combination therapy but not with methotrexate, mycophenolate mofetil, intravenous cyclophosphamide, rituximab, azathioprine, or cyclosporine individually.

Post-Transplant Cyclophosphamide and Tacrolimus–Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors

Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors. GVHD prophylaxis included combination post-HCT cyclophosphamide 50 mg/kg (days +3 and +4) and tacrolimus/mofetil mycophenolate (T/MMF) (day +5 forward). The primary objective was the cumulative incidence of acute and chronic GVHD. Between March 2011 and May 2015, 35 consecutive patients received the proposed regimen. MMF was stopped in all patients at day +28; the median discontinuation of tacrolimus was day +113. Acute and chronic GVHD cumulative incidences were 17% and 7%, respectively, with no grade IV GVHD events, only 2 patients requiring chronic GVHD immunosuppression control, and no deaths from GVHD. Two-year NRM, overall survival, event-free survival, and chronic GVHD event-free survival rates were 3%, 77%, 54%, and 49%, respectively. The graft-versus-tumor effect was maintained as 5 of 15 patients (33%) who received HCT with evidence of disease experienced further disease response. A post-transplant cyclophosphamide + T/MMF combination strategy effectively prevented acute and chronic GVHD after alloPBSCT from HLA-matched donors and achieved an unprecedented low NRM without losing efficacy in disease control or impaired development of the graft-versus-tumor effect. This trial is registered at clinicaltrials.gov as NCT02300571.

A Prospective Randomized, Comparative Trial of High-Dose Mizoribine Versus Mycophenolate Mofetil in Combination With Tacrolimus and Basiliximab for Living Donor Renal Transplant: A Multicenter Trial.

Our objectives were to compare the clinical outcomes of mizoribine (12 mg/kg/d) and mycophenolate mofetil (2000 mg/d) in combination with tacrolimus, basiliximab, and corticosteroids. We enrolled 83 recipients of living-donor renal transplant (performed between 2008 and 2013) in this study. This prospective multi-institutional randomized comparative study compared mizoribine (n = 41) and mycophenolate mofetil (n = 42) in combination with tacrolimus, basiliximab, and corticosteroids for living-donor renal transplant recipients. We compared the acute rejection and graft survival rates and adverse event rates within 1 year of renal transplant between the 2 groups using intention-to-treat analyses. During the 1-year observation period, patient and graft survival rates were 100%. The acute rejection rate was 17.1% in the mizoribine group and 19% in the mycophenolate mofetil group. The incidence rate of cytomegalovirus infection seropositivity (recipient and donor with positive cytomegalovirus antibody status) was higher in the mycophenolate mofetil group than in the mizoribine group, although the difference in these rates was not statistically significant. The incidence of leukopenia was higher in the mizoribine group than in the mycophenolate mofetil group. High-dose mizoribine at 12 mg/kg/day was a safe and efficacious immunosuppressive alternative to mycophenolate mofetil in living-donor renal transplant recipients. Leukopenia should be closely monitored in the initial period of insufficient kidney function after renal transplant.

Azathioprine versus Mycophenolate Mofetil in combination with anti-TNF alpha agents in the management of Crohn's Disease

Background: Combination therapy of biologics and immunomodulators is sometimes necessary in chronically active Crohn's disease to achieve remission and prevent further complications. Treatment escalation in patients who are intolerant to thiopurines can be very challenging as there are few alternative immunosuppressive agents. In this study we evaluate mycophenolate mofetil in combination with an anti-TNF alpha agent in patients who are intolerant to azathioprine.