Mycophenolate Mofetil Dose Research Articles

Use of mycophenolate mofetil in patients with pediatric and adult primary nephrotic syndrome: information from a Japanese hospital claims database

BackgroundCurrent treatment for frequently relapsing, steroid-dependent, or steroid-resistant nephrotic syndrome focuses on immunosuppressive therapies. Although the clinical guideline suggests the use of mycophenolate mofetil (MMF), limited information is available on patients with primary nephrotic syndrome who receive off-label treatment with MMF in Japan.MethodThe dose, treatment duration, previous treatment, and characteristics of primary nephrotic syndrome patients receiving MMF were investigated using data from a Japanese hospital claims database (April 2008–September 2021).ResultsData on 424 primary nephrotic syndrome patients receiving MMF (146 patients < 18 years old; 278 patients ≥ 18 years old) were captured. The most common initial daily doses of MMF capsules (% of patients < 18 and ≥ 18 years old) were 1000 mg (31.9%, 36.8%), 1500 mg (16.0%, 23.8%), and 500 mg (23.6%, 17.3%), and the most common maximum daily doses were 1000 mg (43.8%, 32.9%), 1500 mg (23.6%, 28.9%), and 2000 mg (6.3%, 16.2%). Most patients (97.9%, 99.3%) were treated with a daily dose of 2000 mg or less. Among patients < 18 years old, the younger the patient, the lower the dose. MMF was used for more than 1 year in 30.8% of patients < 18 years old and in 28.8% of patients ≥ 18 years old.ConclusionsOur study suggested that off-label use of MMF for primary nephrotic syndrome has increased since 2012 in Japan. The dose of MMF used in patients with primary nephrotic syndrome was generally within the approved dose range for lupus nephritis and transplant-related diseases in Japan.

The efficacy and safety of mycophenolate mofetil in Thai neuromyelitis optica spectrum disorder patients

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) often leaves patients with a residual disability after each attack. Several studies have demonstrated that mycophenolate mofetil (MMF) effectively prevents relapse in NMOSD. So far, there has been no data on the effectiveness, dosage, and safety of MMF in the Thai population. ObjectivesTo analyze the efficacy and safety of MMF in Thai NMOSD patients. Materials and methodsWe performed a retrospective review of NMOSD patients at Siriraj Hospital from January 1994 to December 2020. The primary outcomes were changes in annualized relapse rate (ARR) and time to relapse after MMF. Pre- and post-MMF Expanded Disability Status Scale (EDSS) scores and visual functional system scores were also compared. ResultsFifty-eight NMOSD patients taking MMF were included. The median dose required was 1,250 (IQR 1,000 – 1,500) mg/day or 23.1 (IQR 17.6–30.8) mg/kg/day. Thirty-five patients (65.5%) were relapse-free after MMF with a median follow-up period of 46.8 months (IQR 24.0–60.9). The median ARR was reduced from 0.80 (IQR 0.45–1.39) to 0 (IQR 0–0.31) after MMF treatment (p < 0.001). Over 90% had either stabilized or improved EDSS. The median EDSS score decreased from 3.5 (IQR 3–6) to 3 (IQR 2–6) (p = 0.004). Nine patients experienced adverse events from MMF, with lymphopenia and infection observed in 8.6% and 5.1% of the cohort, respectively. No serious adverse events were observed. A subgroup analysis of 25 patients switching to MMF after azathioprine failure showed a significant ARR and EDSS reduction. ConclusionsMMF is effective for relapse prevention in Thai NMOSD patients and has a low risk of adverse events. It could be a salvage therapy for patients with azathioprine failure.

Comparison of Long-Term Use of Low Dose Rituximab and Mycophenolate Mofetil in Chinese Patients With Neuromyelitis Optica Spectrum Disorder

BackgroundSeveral studies have reported the efficacy and safety of rituximab (RTX) and mycophenolate mofetil (MMF) in neuromyelitis optica spectrum disorder (NMOSD). This study aimed to evaluate the efficacy and safety of long-term use of low-dose RTX and MMF in Chinese patients with NMOSD.MethodsWe retrospectively reviewed data from patients with NMOSD in our hospital. The enrolled patients were administrated different immunosuppressive agents. We accessed annual relapse rate (ARR), neurological disability (Expanded Disability Status Scale, EDSS), time to the next relapse, and adverse events.ResultsEDSS and ARR were both reduced after RTX and MMF treatment. Kaplan-Meier analysis indicated that patients treated with RTX had a longer time to next relapse compared other immunosuppressive agents before RTX (log-rank test: p < 0.001). Furthermore, we evaluated the change of EDSS and ARR in RTX and MMF, and patients treated with RTX showed a better reduction. Eleven relapses from seven patients in group RTX and 20 relapses from 14 patients in group MMF were reported during follow-up.ConclusionLong-term using of low dose of RTX and MMF were effective and tolerable in Chinese patients with NMOSD. Compared with MMF, RTX showed a better way to reduce the ARR.

Alternative lineage B cells utilizing fatty acid oxidation predict response to third dose COVID vaccination in solid organ transplant recipients

Abstract Solid organ transplant recipients (SOTRs) demonstrate reduced seroconversion and increased breakthrough infection rates following standard two dose mRNA vaccination against SARs-CoV-2. However, within a prospective cohort of SOTRs, the majority of patients (72%) developed a positive anti-Spike (S) IgG following a third vaccine dose, compared to only 15% following two doses. Those who failed to respond to vaccination uniformly received mycophenolate mofetil (MMF). To better understand mechanisms underlying divergent vaccine responses, both global and S-specific B cells were evaluated using flow cytometry to assess immunologic and metabolic phenotypes. Prior to the third dose, 76% of SOTRs demonstrated detectable S-specific B cells even though only 15% had positive anti-S IgG titers. However, B cells were skewed towards a non-class switched phenotype in SOTRs compared to healthy controls. Response to a third dose was predicted by expanded populations of germinal center (GC)-like B cells and CD11c+ alternative lineage B cells with upregulation of carnitine palmitoyltransferase 1a (CPT1a), the rate limiting enzyme for fatty acid oxidation (FAO), a preferred energy source of GC B cells. SOTRs receiving high dose MMF demonstrated significantly lower expression of CPT1a compared to healthy controls, indicating an energetic deficit associated with MMF and failure to respond. Further, in vitro treatment of B cells with MMF reduced the ability to oxidize fatty acids and induced an accumulation of intracellular lipid droplets. Together, these data define alternative lineage B cells present in those who respond to a third vaccine dose, outlining FAO as a metabolic pathway that could be targeted to improve vaccine responses.

Effect of mycophenolate mofetil dose on antibody response following initial SARS-CoV-2 vaccination in patients with systemic sclerosis.

Effect of mycophenolate mofetil dose on antibody response following initial SARS-CoV-2 vaccination in patients with systemic sclerosis.

Tolerability of mycophenolate mofetil in elderly kidney transplant recipients: A retrospective cohort study

Optimal immunosuppression in elderly kidney transplant recipients (KTRs) is not well defined, with mycophenolate mofetil (MMF) being poorly tolerated. Study aim was to compare MMF dose reduction incidence and reason(s) in elderly vs. nonelderly KTRs in the 1st year after transplant with a protocol dose of 1g/day. In this single-center retrospective study, first or repeat KTRs receiving rabbit antithymocyte globulin (rATG), MMF 1g/day, tacrolimus, and prednisone, were stratified by age [≥60 (elderly) or <60 years (nonelderly)]. Primary outcome was MMF dose reduction incidence in the first year. Secondary outcomes included dose reduction rationale, 1-year patient and graft survival, graft function, rejection, infection, hospital presentation, and time to dose reduction. Of 335 KTRs, dose reduction incidence was significantly greater in the elderly group (66% and 54%, p=0.04), though this did not remain significant when adjusted for sex, race, and valganciclovir use. Most common rationale was leukopenia in the elderly group and CMV in the nonelderly group. There were no significant differences in secondary outcomes. Mycophenolate mofetil 1g/day was poorly tolerated in both elderly and nonelderly KTRs receiving lymphocyte-depleting induction with a high incidence of dose reductions; however, no short-term adverse graft outcomes were identified.

Serologic response to a third dose of an mRNA-based SARS-CoV-2 vaccine in lung transplant recipients

Lung transplant recipients have an increased risk for severe coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A third dose of a SARS-CoV-2 vaccine has been recommended for all solid organ transplant recipients, but data from lung transplant recipients specifically are scarce. In this study, the serologic response to a third dose of an mRNA-based SARS-CoV-2 vaccine was measured in 78 lung transplant recipients. Sixty-two percent (n = 48) had a serological response to vaccination, which was significantly higher than after the second vaccine dose (27 patients (35%); p = 0.0013). A positive serologic response was associated with having had COVID-19 (p = 0.01), and higher serum IgG level and complement mannose binding lectin pathway activity prior to vaccination (p = 0.04 and p = 0.03, respectively). Serologic response was not associated with the dose of mycophenolate mofetil or prednisone or other immune status parameters. Eleven patients (14%) developed COVID-19 after the second or third vaccine dose, but this did not associate with serologic response after the second vaccine dose (9% in patients who developed COVID-19 versus 39% in patients who did not develop COVID-19 (p = 0.09)), or with serologic response above cut-off values associated with clinical protection in previous studies. In conclusion, the response to mRNA-based SARS-CoV-2 vaccines in lung transplant recipients improves significantly after a third vaccine dose. Factors associated with a positive serologic response are having had COVID-19 prior to vaccination, and serum IgG and complement mannose binding lectin pathway activity prior to vaccination. Serologic response did not associate with clinical protection against COVID-19 in this study.

BK Virus Nephropathy in HIV-Positive Heart-Kidney Transplant Recipient

<h3>Introduction</h3> BK viral reactivation is common in immunosuppressed states such as advanced HIV and organ transplantation. An important cause of kidney transplant allograft dysfunction and loss is BK reactivation leading to BK virus-associated nephropathy (BKVAN). We describe a problematic case of BKVAN in a combined heart-kidney transplant (HKT) recipient with well controlled HIV. <h3>Case Report</h3> A 46-year-old man with HIV (CD4 726 cells/mm³, HIV viral load <20 copies/mL) on dolutegravir/rilpivirine, non-ischemic cardiomyopathy, and HIV nephropathy underwent HKT with basiliximab induction and maintenance tacrolimus (goal 5-8 ng/mL), mycophenolate mofetil (MMF), and prednisone. Immediate post-transplant course was complicated by delayed renal graft function with acute tubular necrosis and urine leak. HIV has remained well controlled. Post-transplant nadir CD4 count was 639 cells/mm³. The patient developed BK viuria (90,891,555 copies/mL) and BK viremia (4,500 copies/mL) on post-transplant day (PTD) 55 and 62, respectively. Although MMF dose was reduced from 1,000 mg to 500 mg daily, renal allograft biopsy shortly after showed Class B1 BKVAN with no evidence of rejection. Patient began bi-weekly 5 mg/kg cidofovir infusions. Prednisone was decreased from 10 mg to 5 mg daily. Mycophenolate was further reduced to 250 mg daily and steroids were discontinued due to persistently high BK viral load. However, after decline in ejection fraction (EF) to 50% and suspicion for cardiac graft rejection, MMF dose was increased back to 500 mg daily. Endomyocardial biopsies have shown no evidence of rejection with negative donor specific anti-HLA antibodies. Renal function declined with serum creatinine (SCr) peaking at 2.28 mg/dL. Patient has remained on cidofovir infusions and reduced immunosuppression, on which SCr has stabilized to 1.8 mg/dL on PTD 694. Cardiac allograft function remains normal with an EF of 71% on PTD 644. BK viral load peaked at 16,672,298 copies/mL and remains elevated at 4,821 copies/mL on PTD 702. <h3>Summary</h3> We present a case of BKVAN in a HIV+ HKT recipient. This case demonstrates the difficulty of BKVAN management in dual organ transplant since heart allograft management requires higher levels of maintenance immunosuppression. It is unclear if HIV contributed to development of BKVAN in this recipient. Better antiviral therapies are needed for control of BK virus infections after transplant.

Carfilzomib versus Rituximab for Treatment of De Novo Donor Specific Antibodies in Lung Transplant Recipients

<h3>Purpose</h3> De novo donor-specific antibodies (DSA) increase the risk of chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTRs). Both carfilzomib (CFZ) and rituximab (RTX) lower the mean fluorescent intensity (MFI) of DSA; however, a comparison of these two agents in LTRs has not been performed. We compared the degree and duration of DSA depletion with CFZ- and RTX-based treatment strategies. <h3>Methods</h3> LTRs that received CFZ or RTX for DSA depletion between 08/01/2015 and 08/31/2020 were included. The primary outcome was change in MFI (ΔMFI) at corresponding loci before and within 6 months of treatment. Secondary outcomes were time to DSA rebound, change in % predicted FEV1 (ΔFEV1) 6 months after treatment, and CLAD-free survival. <h3>Results</h3> We identified 44 LTRs treated with either CFZ or RTX. As 7 LTRs had ≥2 drug events, 53 drug events were identified and divided into 2 groups, CFZ (32%, n=17) and RTX (68%, n=36). The median time from transplant to detection of DSA was 3 months (1, 24). Use of plasmapheresis (PLEX) and IVIG and increases in mycophenolate mofetil (MMF) dose were equivalent in both groups (PLEX, 97% vs 94%, p=0.580; IVIG, 94.4% vs 94.1%, p=0.962; MMF dose increase 61.1% vs 76.5%, p=0.270). Both drugs significantly lowered the MFI at the DQ locus (Figure 1A, 1B), and the median ΔMFI was comparable. The median interval to DSA rebound was shorter in the CFZ group (4.8 vs 15.6 months, p=0.002). Baseline FEV1 and ΔFEV1 after drug administration were lower in the CFZ group than the RTX group (p<0.001 and p=0.002, respectively). CLAD-free survival with a single RTX event was superior to ≥2 drug events (p=0.001) but was comparable with a single CFZ event (p=0.399; Figure 1C). <h3>Conclusion</h3> While both CFZ and RTX reduced the MFI of circulating DSA, RTX prolonged the time to DSA rebound. Despite more pronounced improvement in FEV1 with RTX, CLAD-free survival was comparable in the 2 groups suggesting that both drugs offer a reasonable treatment strategy for DSA in LTRs.

Two Cases of BK Polyoma Virus Nephropathy in Patients with Isolated Heart Transplantation: Clinical Usefulness of Urinary Cytology

<h3>Introduction</h3> BK polyoma virus (BKpV) nephropathy (BKpVN) has been often reported in patients with kidney transplantation, whereas reports regarding BKpVN in patients with heart transplantation (HTx) is still sparse. <h3>Case Report</h3> We recently encountered two patients who developed BKpVN after HTx. Both patients (Case 1 and 2) coincidentally received HTx at the age of 56. A standard triple-drug regimen consisting of tacrolimus, mycophenolate mofetil (MMF), and a corticosteroid was started after surgery and the regimen was converted to everolimus (EVL) with reduced tacrolimus within 6 months after HTx because of donor transmitted atherosclerosis in both patients. Case 1 further underwent percutaneous coronary intervention 3.5 years after HTx. Despite renal-sparing immunosuppresion, values of creatinine begun to increase after HTx in both patients and they were diagnosed with BKpVN through high viral DNA copy number in the urine and blood. Regarding case 1, pathological analysis of kidney biopsy specimens disclosed interstitial infiltrate with lymphocytes associated with tubular injury which also lead to the diagnosis of BKpVN. Retrospectively, both patients were positive for decoy cell within 1 year after HTx therefore, these patients should have been recognized as high risk for BKpVN. After the diagnosis of BKpVN, immunosuppressive regimen of them was further changed to minimum dose of EVL (a trough concentration of 6-7 ng/ml) and MMF (500 mg daily) respectively under the guidance of myocardial biopsy and they have been uneventful for over a year after the diagnosis of BKpVN despite severe chronic kidney disease. <h3>Summary</h3> We presented two rare cases of BKpVN after HTx. In our institution, urinary cytology is regularly examined if there are decoy cells which we think are the sign of over immunosuppression. However, decoy cells detected by urinary cytology also suggest that there is subclinical BKpV infection. Urinary cytology, a noninvasive and cost-effective examination, should be routinely performed for the risk assessment of BKpVN even in HTx patients, since detecting decoy cell would be helpful for the early diagnosis of BKpVN.

Risk Assessment of Neutropenia during Low-Dose Valganciclovir Prophylaxis for Heart Transplant Recipients.

The aim of this study was to investigate whether low-dose valganciclovir (VGCV) prophylaxis for cytomegalovirus (CMV) infection increased the risk of developing neutropenia in heart transplant recipients (HTRs). Forty-three HTRs receiving VGCV were divided into two groups: those who received VGCV prophylaxis (n = 22) and those who did not (n = 21). Neutropenia was defined as an absolute neutrophil count ˂1500/µL and was monitored for approximately one year post-transplantation. In the prophylaxis group, 77.3% (17/22) of HTRs experienced neutropenia, which was significantly higher than that in the no prophylaxis group (42.9% [9/21], p = 0.031). No significant differences in the duration of VGCV administration and cumulative dose up to the first neutropenia episode were observed between the groups. Meanwhile, the cumulative dose of mycophenolate mofetil was significantly higher in the prophylaxis group than in the no prophylaxis group (p = 0.018); the daily maintenance dose and regularly measured area under the concentration-time curve (AUC) of mycophenolic acid did not significantly differ between groups. In conclusion, the risk of developing neutropenia was higher in HTRs receiving low-dose VGCV prophylaxis than it was in those not receiving prophylaxis, probably not attributed to dosing period and cumulative dose of VGCV until the onset of neutropenia.

Evaluation of Mycophenolate Dose Reductions within the First Year After Lung Transplantation and Outcomes

<h3>Purpose</h3> Mycophenolate mofetil (MMF) significantly decreases acute rejection after lung transplant, however, adverse side effects commonly lead to dose reductions (DR) or temporary discontinuations (tDC). The primary aim of this study is to characterize the impact on ACR (acute cellular rejection) rates and to secondarily characterize the incidence and reasons for DR or tDC. <h3>Methods</h3> A single center retrospective chart review was conducted on patients who received a lung transplant between 7/20/16-2/10/19. Patients who died within index hospitalization or did not discharge on MMF were excluded. Severe leukopenia was defined as WBC<3.0 and all mycophenolic acid doses were converted to MMF equivalents. <h3>Results</h3> A total of 106 patients were included (11 patients excluded for death at index hospital admission or were not discharged on MMF). Seventy-eight (73.5%) patients had MMF dose reductions within the first year with a reduction to the lowest average daily dose of 605mg (±241), and leukopenia was the leading indication (76%) (Table 1). Age greater than 65 was significantly associated with higher incidence of severe leukopenia (27/55, 49%) (p=0.043) leading to DR or tDC. <h3>Conclusion</h3> While there is high incidence of MMF DR or tDC within the first year post transplant, there was no associations with ACR or development of DSAs. Older age was associated with more severe leukopenia and may warrant lower target doses without increasing ACR episodes.

Two-year outcomes of low-exposure extended-release tacrolimus and mycophenolate mofetil regimen in de novo kidney transplantation: A multi-center randomized controlled trial.

Once-daily extended-release tacrolimus (TACER) is commonly administered following kidney transplantation (KTx); however, its optimal dosage remains unknown. In this multi-center, randomized controlled trial, 62 living donor KTx recipients were assigned to either standard-exposure (SE; n=32) or low-exposure (LE; n=30) TACER (Graceptor®, Astellas Pharm Inc.) groups. All patients received basiliximab and mycophenolate mofetil (MMF). The primary outcomes were acute rejection, graft/patient survival, and the secondary outcomes were incidence of cytomegalovirus infection, and de novo donor-specific antibodies (dnDSA) production. The tacrolimus trough level and estimated area under the blood concentration-time curve (eAUC) were significantly higher in SE than in LE (SE vs. LE; 1 year: 5.0 ± 0.9ng/ml and 206.9 ± 26.8 ng h/ml vs. 3.4 ± 1.0ng/ml and 153.9 ± 26.4 ng h/ml; 2 years: 4.8 ± 1.0ng/ml and 204.9 ± 30.1 ng h/ml vs. 3.8 ± 0.9ng/ml and 164.4 ± 27.0 ng h/ml). In contrast, the dosage and eAUC of MMF did not differ between groups. Two-year graft and patient survival rates were 100% in both groups, and acute rejection rates were 0% and 10% in the SE and LE, respectively (p=0.11). The mean estimated glomerular filtration rates did not differ between the groups. Cytomegalovirus infection was slightly lower in the LE (SE: 12.5% and LE: 6.7%, p=0.37). In the LE, four cases of dnDSA were noted within 2 years of transplantation; no case was observed in the SE (p=0.034). Although the LE TACER regimen showed similar rates of acute rejection, as well as graft and patient survival compared with SE after KTx, LE was significantly more associated with dnDSA. Further investigation of its long-term effect on graft survival is warranted. (University Hospital Medical Information Network Clinical Trials Registry ID: UMIN000033089).

Past COVID-19 and immunosuppressive regimens affect the long-term response to anti-SARS-CoV-2 vaccination in liver transplant recipients

Background & AimsThe long-term immunogenicity of anti-SARS-CoV-2 vaccines in liver transplant (LT) recipients is unknown. We aimed to assess the long-term antibody response of the Pfizer-BioNTech® BNT162b2 vaccine in LT recipients compared to controls.MethodsLT recipients underwent anti-SARS-CoV-2 anti-receptor-binding domain protein IgG (anti-RBD) and anti-nucleocapsid protein IgG antibody (anti-N) measurements at the first and 1, 4 and 6 months after the second vaccination dose.ResultsOne hundred forty-three LT recipients and 58 controls were enrolled. At baseline, 131/143 (91.6%) LT recipients tested anti-N negative (COVID-19 naïve), and 12/143 (8.4%) tested positive (COVID-19 recovered) compared to negative controls. Among COVID-19 naïve, 22.1% were anti-RBD positives 1 month after the first vaccine dose, while 66.4%, 77%, and 78.8% were 1, 4 and 6 months following the second vaccine dose. In contrast, 100% of controls were positive at 4 months (p <0.001). The median anti-RBD titer 4 months after the second vaccine dose was significantly lower (32 U/ml) in COVID-19 naïve than in controls (852 U/ml, p <0.0001). A higher daily dose of mycophenolate mofetil (MMF) (p <0.001), higher frequency of ascites (p = 0.012), and lower serum leukocyte count (p = 0.016) were independent predictors of anti-RBD negativity at 6 months. All COVID-19 recovered patients tested positive for anti-RBD at each time point. The median antibody titer was similar in those taking MMF (9,400 U/ml, 11,925 U/ml, 13,305 U/ml, and 10,095 U/ml) or not taking MMF (13,950 U/ml, 9,575 U/ml, 3,500 U/ml, 2,835 U/ml, p = NS) 3 weeks after the first and 1, 4 and 6 months after the second vaccine dose, respectively.ConclusionsIn COVID-19-naïve LT recipients, the immunogenicity of anti-SARS-CoV-2 vaccination was significantly lower than that in controls. MMF was the main determinant of vaccination failure in SARS-CoV-2-naïve patients.Lay summaryThe immunogenicity of anti-SARS-CoV-2 vaccination in liver transplant recipients is currently unknown. Herein, we show that liver transplant recipients who have not previously had COVID-19 are less likely to mount effective antibody responses to vaccination than a control population. The main determinant of vaccination failure was the use of the immunosuppressive drug mycophenolate mofetil.

Intensity of mycophenolate mofetil treatment is associated with an impaired immune response to SARS-CoV-2 vaccination in kidney transplant recipients

Kidney transplant recipients (KTRs) are extremely vulnerable to SARS‐CoV‐2 infection and show an impaired immune response to SARS‐CoV‐2 vaccination. We analyzed factors related to vaccination efficiency in KTRs. In a multicenter prospective observational study (NCT04743947), IgG antibodies levels against SARS‐CoV‐2 spike S1 subunit and their neutralization capacity after SARS‐CoV‐2 vaccination were analyzed in 225 KTRs and compared to 176 controls. After the vaccination, 56 (24.9%) KTRs became seropositive of whom 68% had neutralizing antibodies. This immune response was significantly lower compared to controls (239 [78–519] BAU/ml versus 1826 [560–3180] BAU/ml for KTRs and controls, p < .0001). The strongest predictor for an impaired response was mycophenolate mofetil (MMF) treatment. Multivariate regression analysis revealed that MMF‐free regimen was highly associated with seroconversion (OR 13.25, 95% CI 3.22–54.6; p < .001). In contrast, other immunosuppressive drugs had no significant influence. 187 out of 225 KTRs were treated with MMF of whom 26 (13.9%) developed antibodies. 23 of these seropositive KTRs had a daily MMF dose ≤1 g. Furthermore, higher trough MMF concentrations correlated with lower antibody titers (R −0.354, p < .001) supporting a dose‐dependent unfavorable effect of MMF. Our data indicate that MMF dose modification could lead to an improved immune response.

Is the failure of recent trials on withdrawal of calcineurin inhibitors due to inadequate mycophenolic acid dosing?

Calcineurin inhibitors (CNIs) are the mainstay immunosuppressive therapy after kidney transplantation, despite their side effects. Recently, several randomized controlled trials attempting CNI withdrawal or minimization in stable, low-risk kidney transplant recipients led to an unacceptable risk of acute rejection and de novo HLA antibody formation. In the opinions of many, these trials definitively demonstrated that CNI-free regimens in the context of mycophenolate mofetil (MMF) maintenance are too risky. It can be argued, however, that the investigators failed to optimize the dose of the remaining immunosuppressive therapy. In particular, the potential benefit of MMF dosing based on the targeted mycophenolic acid (MPA) concentration was not taken into account. In this review, we present an overview of the studies on CNI withdrawal, both recent and older, paying specific attention to the MMF dose and elaborating on the possible benefit of MPA monitoring in this setting.

Risk of Cytomegalovirus Infection with Post-Transplantation Cyclophosphamide in Haploidentical and HLA-Matched Unrelated Donor Transplantation

Post-transplantation cyclophosphamide (PTCy) is effective for graft-versus-host disease (GVHD) prevention but is associated with an increased risk of cytomegalovirus (CMV) infection. The effect of PTCy on CMV infection in matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) is unclear, and whether there is any difference in CMV risk with 1 or 2 doses of PTCy is not well established. This study aimed to compare the incidence of CMV infection and the association between T cell recovery in patients who received PTCy-based GVHD prophylaxis and those who received non-PTCy-based GVHD prophylaxis. We conducted a retrospective study to compare the risk of CMV infection in 3 cohorts: cohort A (n=94), matched related donor (MRD)/MUD HSCT with calcineurin inhibitor-based GVHD prophylaxis; cohort B (n=103), MRD/MUD HSCT with 1 dose of PTCy, tacrolimus, and mycophenolate mofetil (MMF); and cohort C (n=28), haploidentical donor HSCT with 2 doses of PTCy, tacrolimus, and MMF. The day +100 cumulative incidence of CMV infection was 29% for cohort A, 39% for cohort B, and 61% for cohort C (P=.009), with no difference among the cohorts in the duration of viremia (P=.46). CD3+ and CD4+ T cell counts were significantly higher in cohort A at day +30 but not at days +60 and +90. Nonrelapse mortality (NRM) trended higher and relapse was significantly lower with PTCy. There was no difference in survival among the 3 cohorts. There is an increased risk of early CMV infection in patients receiving PTCy irrespective of donor type and number of PTCy doses compared with those not receiving PTCy. Strategies focusing on CMV prevention in PTCy recipients to mitigate the risk of NRM may lead to improved long-term outcomes.

Simple Vaccination Is not Enough for the Transplant Recipient.

Simple Vaccination Is not Enough for the Transplant Recipient.

Persistent headache in a young kidney transplant recipient caused by tacrolimus associated pseudotumor cerebri - A case report

Pseudotumor cerebri (PC) is characterized by chronic elevation of intracranial pressure with normal cerebrospinal fluid (CSF) examination and normal neuro-imaging. We report a case of a 22-year-old female with renal allograft and for the past 4 years on immunosuppressant including prednisolone, tacrolimus, and mycophenolate mofetil. The patient presented with persistent headache for 2 months along with nausea and vomiting. Fundoscopic examination revealed bilateral papilledema. Magnetic resonance imaging-brain with venogram was normal and cytochemical examination of CSF was also normal. Ocular coherence tomography revealed increased retinal nerve fiber layer thickness. A diagnosis of PC was made based on an elevated CSF pressure (35 cm H20). We reduced the dose of tacrolimus and added acetazolamide but the dose of prednisolone and mycophenolate mofetil was not modified. There was the gradual improvement of symptoms. On follow-up visits, papilledema disappeared and the patient is now asymptomatic with normal allograft function.

Use of mycophenolate mofetil for systemic sclerosis and systemic sclerosis-associated interstitial lung disease: Information from a Japanese hospital claims database.

Limited information is available on patients with systemic sclerosis (SSc) or SSc-associated interstitial lung disease (SSc-ILD) receiving mycophenolate mofetil (MMF) in Japan. The dose, treatment duration, and patient characteristics of SSc and SSc-ILD patients receiving MMF were investigated. We used data from a Japanese hospital claims database (2008-2020). Data on 486 SSc patients ≥18 years old receiving MMF were captured; 314 had SSc complicated with ILD. The most common initial daily doses were 1000 mg (SSc, 39.5%; SSc-ILD, 38.1%) and 500 mg (SSc, 36.6%; SSc-ILD, 34.6%). The most common maximum daily doses were 1000 mg (SSc, 33.3%; SSc-ILD, 34.9%), 1500 mg (SSc, 24.4%; SSc-ILD, 23.1%), and 2000 mg (SSc, 23.8%; SSc-ILD, 24.4%). Doses ranged from 250 to 3000 mg/day and were similar for SSc and SSc-ILD patients. Over 27% of patients received treatment for >1 year. There was a gradual decrease in steroid doses during MMF treatment. Our study suggests that the off-label use of MMF for SSc and SSc-ILD has been increasing annually since 2015 in Japan. The doses used in patients with SSc and SSc-ILD were similar to the approved doses of MMF for lupus nephritis in Japan.