Mycophenolate Mofetil Dose Reduction Research Articles

Safety and Efficacy of a Preemptive Mycophenolate Mofetil Dose Reduction Strategy in Kidney Transplant Recipients.

There are no high-quality data to guide long-term mycophenolate mofetil (MMF) dosing in kidney transplant recipients (KTRs) to balance the long-term risks of allograft rejection with that of infections and malignancy. At our center, KTRs are managed with either a "preemptive" dose reduction strategy, where the MMF dose is reduced after the first year before the development of adverse events, or with a "reactive" dosing strategy, where they are maintained on the same MMF dose and only reduced if they develop an adverse event. We hypothesized that a preemptive MMF dosing strategy after the first year of transplantation is associated with decreased infections without increasing alloimmune complications. We conducted a retrospective cohort study of all KTRs receiving MMF from January 1, 2015, to December 31, 2020. The primary outcome was the incidence of infections requiring hospitalization. One hundred forty-two KTRs met the inclusion criteria, of whom 44 (31%) were in the preemptive group and 98 (69%) were in the reactive group. The median follow-up was 4 y (interquartile range, 3.8-4.0). Multivariable analysis showed that a preemptive MMF dose reduction strategy was associated with a lower risk of infections requiring hospitalization (adjusted hazard ratio = 0.39; 95% confidence interval, 0.16-0.92). There was no difference in graft loss, rejection, or estimated glomerular filtration rate slope. Preemptive MMF dose reduction in KTRs may be an effective strategy to prevent infections without increasing the risk of allograft rejection. Randomized clinical trials are needed to confirm these findings.

Protocolized polyoma BK viral load monitoring and high-dose immunoglobulin treatment in children after kidney transplant.

BKPyV virus nephropathy (BKPyVAN) is diagnosed in 5%-16% of pediatric renal transplant recipients (PRTR) and preceded by BKPyV-viruria and DNAemia. Despite the risk of irreversible transplant damage associated with BKPyVAN, evidence-based consensus guidelines for BKPyVAN prevention are still lacking. In this retrospective study, we examined the safety and efficacy of high-dose intravenous immunoglobulin (HD-IVIG) therapy for prevention of BKPyVAN in PRTR with significant BKPyV-viruria/DNAemia. Between January 2013 and December 2022, all PRTR under our care underwent routine urine and blood testing for BKPyV viral load, using specific polymerase chain reaction (PCR). BKPyV DNAemia, with<103 copies/mL, with BKPyV viruria<107 copies/mL, with no evidence of BKPyVAN, were managed with 50% dose reduction of mycophenolate mofetil (MMF). Patients showing no decline in BKPyV viral load within two months of MMF dose reduction were managed with HD-IVIG (2g/kg). Seventy patients were recruited during a ten-year period and 31/70 patients (44%) demonstrated significant post-transplantation BKPyV-viruria/DNAemia, while 13/31 (42%) patients were unresponsive to MMF dose reduction, and were administered HD-IVIG. Of these, 12/13 (92%) patients achieved BKPyV viral clearance within six months from completion of HD-IVIG therapy and 1/13 patient (8%) was unresponsive to HD-IVIG therapy, showing increased BKPyV viral load. There were no major adverse events associated with HD-IVIG, and none of our patients developed BKPyVAN during the study period. Prophylactic HD-IVIG therapy in PRTR with significant BKPyV-viruria/DNAemia unresponsive to MMF dose reduction is safe and might be effective in preventing BKPyVAN. Our findings remain to be established by large-scale prospective studies.

Impact of Steroid Only Induction on Rejection in Simultaneous Liver-Kidney Transplantation.

Introduction: The occurrence of simultaneous liver kidney transplantation has greatly increased; however, the ideal induction and maintenance immunosuppression remains unknown. Question: This evaluation aimed to determine if corticosteroid only induction in simultaneous liver kidney transplant recipients provided adequate prophylaxis against rejection when compared to basiliximab. Design: This was a single center, retrospective, cohort study of adult simultaneous liver kidney transplant recipients from June 2010 to June 2019 receiving corticosteroid only (N = 41) or basiliximab (N = 42) induction. Results: Liver or kidney biopsy proven acute rejection at 3 months was comparable between the corticosteroid only and basiliximab groups (10% vs 7%, P = .67), which persisted through 12 months posttransplant (15% vs 21%, P = .42). The occurrence of any infection at 3 months was increased in the corticosteroid only group relative to the basiliximab group (41% vs 21%, P = .049). Graft and patient survival at 12 months were similar between groups. Maintenance immunosuppression was overall minimized with a tacrolimus goal of 6-8 ng/mL, mycophenolate mofetil dose reduction to 1000 mg/day by 3 months, and early steroid withdrawal in both groups. Conclusion: Our findings suggested that corticosteroid only induction was an effective strategy for preventing rejection in simultaneous liver kidney transplant recipients, even in combination with reduced maintenance immunosuppression.

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.

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.

Impact of risk-stratified mycophenolate dosing in heart transplantation.

Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid, is a highly effective immunosuppressive agent in heart transplant therapy. While the FDA approved dose is 1500 mg twice daily, dosing is often reduced due to dose-dependent adverse effects. However, empiric MMF dose reductions may lead to sub-therapeutic dosing and impair clinical outcomes. Our single center protocolized a risk-stratified approach based on age and weight to dose 500 mg twice daily or 1000 mg twice daily to patients after heart transplantation. This retrospective single-center study analyzed 140 consecutive heart transplant patients who were initiated on our risk-stratified MMF protocol post-transplant. The analysis revealed that the composite rate of biopsy-proven rejection, graft loss, or mortality at 1-year post-transplantation was similar between the two groups. Incidence of neutropenia, thrombocytopenia, infection, cardiac allograft vasculopathy, or acute kidney injury by 1-year also showed similar results between the two groups. Risk-stratification of MMF dosing appears to be a safe and effective strategy after heart transplantation.

Host-Pathogen Interactions in Human Polyomavirus 7‒Associated Pruritic Skin Eruption

Host-Pathogen Interactions in Human Polyomavirus 7‒Associated Pruritic Skin Eruption

Recurrence of progressive skin involvement following discontinuation or dose reduction of Mycophenolate Mofetil treatment in patients with diffuse Systemic Sclerosis

BackgroundRapidly progressive diffuse cutaneous Systemic Sclerosis (rp-dcSSc) is associated with severe internal organ involvement and high mortality. Mycophenolate Mofetil (MMF) has been shown to halt the progression of rp-dcSSc cutaneous and pulmonary involvement in observational and randomized controlled trials, respectively. However, optimal MMF therapy duration has not been established. Here, we describe the clinical evolution of rp-dcSSc patients successfully treated with MMF following MMF therapy discontinuation or dose reduction. MethodsTwenty-five patients with recent-onset (< 24 mo) rp-dcSSc received MMF as the only SSc disease-modifying therapy. Following MMF discontinuation or dose reduction to or below 1000 mg/day after an average of two years, the Modified Rodnan skin score (mRSS) and Pulmonary function tests (PFT) were serially evaluated for additional 5 years. MMF therapy was re-instituted if the mRSS increased by greater than 20% or if restrictive lung disease developed. ResultsFrom nineteen patients serially evaluated following MMF discontinuation or dose reduction, five patients (26.3%) developed recurrence of rapid skin involvement with an average of 35.9% increase in mRSS from 7.8 to 10.6 points requiring MMF re-institution. Two of these patients also presented worsening respiratory symptoms and reduction of lung volumes in PFTs. Following MMF resumption, mRSS returned to baseline or stabilized and PFTs improved or stabilized. All these patients were maintained on high dose long term MMF treatment. ConclusionRecurrence of severe skin involvement occurred in 26.3% of patients with rp-dcSSc following MMF discontinuation or dose reduction, requiring prompt MMF therapy resumption. These findings confirm the therapeutic benefit of MMF in rp-dcSSc and suggest that MMF treatment should be maintained for longer than 2 years.

Effect of Age on Leukopenia Following Renal Transplantation at a Single Center.

Leukopenia in renal transplant recipients occurs commonly within the first year following transplantation; however, literature on the effects of age on leukopenia is scarce. A single-center, retrospective review was conducted on 141 recipients transplanted from January 2011 to December 2015. Transplant recipients were characterized by age <60 years (n = 94) or age 60 years and older (n = 47) for analysis. A greater incidence of leukopenia was seen in the older cohort compared to the younger cohort (64% vs 55%). Of those patients who developed leukopenia, the older cohort (n = 30) had a higher incidence of hospitalization for leukopenia (30% vs 23%) but a lower incidence of hospitalization for infection (20% vs 25%) compared to the younger cohort (n = 52). Additionally, one month following mycophenolate mofetil (MMF) discontinuation, the older cohort had reduced recovery of their white blood cell count (+263.8% vs +272.5%) and experienced less recurrent leukopenic episodes (50% vs 67%) and rejection episodes (0% vs 22%) compared to the younger cohort, alluding to the need for less immunosuppression. Age at transplantation was not associated with the development of leukopenia; however, older patients had a higher incidence of leukopenia and hospitalization for leukopenia. Dose reduction or discontinuation of MMF should be considered in older kidney transplant recipients who develop leukopenia.

Correlation between Mycophenolate Dosage and Occurrence of Adverse effects in Renal Transplant Patients

Background Mycophenolate mofetil (MMF) is effective in improvement of graft survival and prevention of acute rejection after kidney transplantation. It has been shown in a study that decreasing MMF dose due to infection does not increase the incidence of rejection or graft failure. However, another study showed dose reduction of MMF had increased acute rejection and poorer long-term graft survival. As there is contradictory evidence regarding the optimal dose of MMF, we studied the correlation between MMF dose and occurrence of adverse effects (infection/rejection) in renal transplant patients. Method This is a retrospective, single centre study on patients who received a renal transplant from 1st January 2011 to 31st December 2013, in our unit. All transplant recipients who was commenced on MMF as part of triple immunosuppression on the first day post-transplant were included and followed up for three years. Information was obtained from hospital electronic records. MMF dosage immediately following transplant, at three, six, 12 and 36 months post transplant were recorded and average dose was calculated. Infection was determined if positive cultures, high inflammatory markers or positive viral loads. Rejection was analysed if biopsy proven. Results There were 165 renal transplants. 74 patients had completed 3-year follow up. Table 1 shows the results.Conclusion A link between dosage of MMF and infection/rejection rates has not been observed in this study. Further data will need to be analyzed for a conclusive result.

Mycophenolate Mofetil Withdrawal With Conversion to Everolimus to Treat BK Virus Infection in Kidney Transplant Recipients

BackgroundBK virus (BKV) is a significant post-transplant infection. Mammalian target of rapamycin inhibitors (mTORis) reduce BKV large T antigen expression in vitro and are associated with lower rates of BKV infection when used as de novo immunosuppression in clinical studies. MethodsWe performed a prospective, single-center, randomized, open label pilot trial to evaluate the impact of mycophenolate mofetil (MMF) withdrawal with conversion to the mTORi everolimus versus a 50% reduction of the MMF dose for the treatment of BKV infection after kidney transplantation. Patients maintained on tacrolimus, MMF, and corticosteroids that developed BK viremia or BK viruria ≥1 × 106 copies/mL were eligible. The primary endpoint was a >50% reduction of BK viruria or clearance of viremia at 3 months postrandomization. ResultsForty patients were enrolled and randomized in a 1:1 manner; 11 (55%) and 8 patients (40%) reached the primary endpoint in the everolimus group and the MMF group, respectively (P = .53). Of those with BK viremia at the time of enrollment, 8 of 16 (50%) and 5 of 15 (33.3%) cleared the viremia by month 3 in the everolimus conversion and MMF dose reduction groups, respectively (P = .47). ConclusionConversion from MMF to everolimus in BKV infection demonstrated a trend toward improved viral clearance but did not reach statistical significance.

A Case Report of the Resolution of Multiple Recalcitrant Verrucae in a Renal Transplant Recipient After a Mycophenolate Mofetil Dose Reduction

Renal transplant recipients are at an increased risk of developing verrucae due to chronic immunosuppression, and certain therapies may confer a greater risk. Herein, we describe a 51-year-old woman with a 10-year-old unrelated kidney transplant who developed numerous therapy-resistant verrucae while on mycophenolate mofetil and tacrolimus maintenance immunosuppression. Over several years of immunosuppressant therapy, she declined the approach of reducing her mycophenolate mofetil dose to potentially improve her verrucae. Unfortunately, she later developed graft rejection requiring reversion to peritoneal dialysis. Within months of reducing her mycophenolate mofetil dose (her tacrolimus dose remained unchanged), she experienced dramatic resolution of many of her verrucae. In the current case, the observed clinical improvement may have resulted from either the total reduction of immunosuppression or the specific reduction of mycophenolate mofetil. Consequently, mycophenolate mofetil may contribute to the refractory nature of verrucae within renal transplant recipients, and further research should determine the relationship between verrucae development and both specific immunosuppressant therapies and the degree of immunosuppression.

Mycophenolate Mofetil (MMF)-Induced Colitis

IntroductionMMF is an immunosuppressive drug frequently used for graft-versus-host disease (GVHD) prophylaxis and management. MMF-induced colitis is a known complication, however, details regarding its clinical manifestations, treatment options, and outcomes are less clear. Differentiating MMF-induced colitis from gut GVHD on the basis of histology may be difficult, hence deeper clinical understanding of MMF-induced colitis can be valuable. The aim of this systematic review was to analyze the reported cases of MMF-induced colitis to provide summative data.MethodsInclusion criteria included prospective or retrospective clinical studies and case series, reported in English language, providing data on clinical manifestations, treatment options, and outcomes of colitis induced by MMF or its derivatives (such as mycophenolic acid, and enteric coated mycophenolate sodium). Cases were included irrespective of the indication of MMF. Using various search terms, all cases indexed in PubMed, EMBASE, Cochrane and Scopus from inception to July 2016 were reviewed. The bibliography of each relevant article was searched for additional reports. Non-human studies and colitis attributed to other etiologies such as infection, GVHD or inflammatory bowel disease were among the 138 articles that were excluded.ResultsForty-four articles with a total of 544 patients and 560 episodes of suspected or confirmed MMF-induced colitis were included. The median age was 41 years (range 5-70), and 30% were females. The latency between the use of MMF and onset of colitis was 990 days (range 3- 5760). Watery diarrhea as frequent as every 20 minutes in one case and large volume at times, was the presenting symptom in 92% of cases. Other less common presentations included bloody diarrhea, abdominal pain, and steatorrhea. MMF was discontinued or dose reduced in 65%, switched to enteric coated mycophenolate mofetil sodium in 14% and continued in 21% of cases. Ninety-eight percent of cases managed with discontinuation or dose reduction of MMF responded to the treatment. About 93% of cases who switched from MMF to enteric coated mycophenolate mofetil sodium responded. Among the patients who continued MMF, diarrhea was persistent in 17% while it resolved spontaneously in 83% (Figure 1).The median time to response to either change to enteric coated mycophenolate sodium or discontinuation of treatment was 20 days (range 1-45).Complications developed in 3.5% (n=19) of cases including graft rejection in solid-organ transplant (n=11) after discontinuation or dose reduction of MMF, acute dehydration (n=6), toxic colitis (n=1), and severe weight loss of >60 pounds (n=1).ConclusionMMF-induced colitis generally presents with watery diarrhea but rarely blood may be noted in stool. The latency period can be as long as months to years, hence a long latency period does not exclude the possibility. A vast majority of patients respond to cessation of MMF or dose reduction within a few weeks, however, cessation of MMF may result in graft rejection. In cases where continuation of immunosuppressive therapy is considered important to prevent graft rejection, alternate management option for management of MMF-induced colitis could include switching to a different drug formulation. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Frailty, mycophenolate reduction, and graft loss in kidney transplant recipients.

Mycophenolate mofetil (MMF) side effects often prompt dose reduction or discontinuation, and this MMF dose reduction (MDR) can lead to rejection and possibly graft loss. Unfortunately, little is known about what factors might cause or contribute to MDR. Frailty, a measure of physiologic reserve, is emerging as an important, novel domain of risk in kidney transplantation recipients. We hypothesized that frailty, an inflammatory phenotype, might be associated with MDR. We measured frailty (shrinking, weakness, exhaustion, low physical activity, and slowed walking speed), other patient and donor characteristics, longitudinal MMF doses, and graft loss in 525 kidney transplantation recipients. Time-to-MDR was quantified using an adjusted Cox proportional hazards model. By 2 years after transplantation, 54% of frail recipients and 45% of nonfrail recipients experienced MDR; by 4 years, incidence was 67% and 51%. Frail recipients were 1.29 times (95% confidence interval [95% CI], 1.01-1.66; P = 0.04) more likely to experience MDR, as were deceased donor recipients (adjusted hazard ratio [aHR], 1.92; 95% CI, 1.44-2.54, P < 0.001) and older adults (age ≥ 65 vs <65; aHR, 1.47; 95% CI, 1.10-1.96, P = 0.01). Mycophenolate mofetil dose reduction was independently associated with a substantially increased risk of death-censored graft loss (aHR, 5.24; 95% CI, 1.97-13.98, P = 0.001). A better understanding of risk factors for MMF intolerance might help in planning alternate strategies to maintain adequate immunosuppression and prolong allograft survival.

(855) - Tacrolimus Monotherapy After Pediatric Heart Transplantation

Routine long-term immunosuppression (IS) after pediatric heart transplantation is based on the combination of tacrolimus (TAC) and mycophenolate mofetil (MMF) or everolimus (EVE). Gastrointestinal side-effects of the MMF and/or recurrent infections related to EVE can indicate the use of TAC monotherapy. The safety of TAC monotherapy was analized. Between 2007-2014 September, 26 pediatric heart transplantations were performed in our institute (age: 3 months-16 years; male/female: 12/14; weight: 4.4-61.5 kg). Tacrolimus monotherapy was indicated in 4 cases due to recurrent side effects (age: 11-23 months; male/female: 3/1; weight: 7.6-11.4 kg). Target level of tacrolimus was determined 2 ng/ml higher than used by combined therapy. Surveillance biopsies and echocardiography were performed to detect rejections. Rejections and incidence of infections were studied retrospectively. In every case the first line therapy was the combination of TAC+MMF. In 3 of them MMF/EVE conversion was indicated due to severe enteral side-effects in spite of MMF dose reduction. TAC target level was reduced on TAC+EVE combination depending on posttransplant time. After the conversion the gastrointesinal symptoms were eliminated, but in all of 3 patients recurrent infections were occured (in 2 patients upper-airway infections, in 1 patient permanent high replication of Ebstein Barr virus developed). In 1 patient on TAC+MMF therapy CMV disease and recurrent CMV activations were detected, indicating the reduction of IS. The main follow-up were 14 months. No side-effects was documented related to higher tacrolimus-level. No rejections were detected on biopsies. Infection rate was significantly reduced in every patients. Reduced immunosuppression could be necessary in small children (<2 yrs of age) due to recurrent side effects of TAC+MMF/EVE therapy. Tacrolimus monotherapy can be a good and safe alternative with higher target level. Long-term follow-up is needed to evaluate chronic rejection.

Hand Transplantation in Its Fourteenth Year: The Innsbruck Experience

Five patients received a bilateral hand (n = 3), a bilateral forearm (n = 1) and a unilateral hand transplant (n = 1) between 03/2000 and 03/2014. We herein describe the long-term outcome with emphasis on function, immunosuppression (IS), histomorphology and graft vascular changes.Induction therapy with antithymocyte globulin or alemtuzumab was followed by tacrolimus, prednisolone ± mycophenolate mofetil (MMF) or tacrolimus and MMF maintenance IS. Later, an mTOR-Inhibitor was added under simultaneous withdrawal or dose reduction of tacrolimus or MMF. Steroids were avoided in one and withdrawn in 2 patients.Range of motion reached up to 70% of normal with a grip strength up to 10kg. Hand function correlated with time after transplantation and amputation level and remained stable after year 5 in all cases. Intrinsic hand muscle function recovery, discriminative sensation and temperature sensation were observed after hand transplantation. Three, 7, 6, 3 and one rejection episodes were successfully treated wi...

Reasons for dose reduction of mycophenolate mofetil during the first year after renal transplantation and its impact on graft outcome

Mycophenolate mofetil (MMF) decreases the risk of acute rejection and is associated with improved graft survival in renal transplant recipients. However, MMF-related side effects often necessitate dose reduction, which may expose patients to a higher risk of acute rejection and graft loss. This study's aim was to examine the reasons for MMF dose reduction during the first post-transplant year and its impact on acute rejection, overall and death-censored graft loss. Single-center retrospective analysis of 749 renal transplant recipients treated with MMF in their initial maintenance immunosuppressive protocol. In 365 patients (48.7%) a total of 530 MMF dose reductions were done. Reasons for reduction were hematologic toxicity (46.5%), infection (16.1%), gastrointestinal side effects (12.3%), malignancy (2.1%), study protocol (14.6%), and unknown (13.5%). MMF dose reduction as such was not an independent predictor of acute rejection or graft survival, although reductions in ≥ 50% of initial dose were significantly associated with acute rejection. In this retrospective cohort, by far the most important reason for MMF dose reduction during the first post-transplantation year was hematologic. MMF dose reductions in ≥ 50% increased the risk of acute rejection but did not compromise graft survival.

Can Mycophenolate Mofetil Be Successfully Tapered in Myasthenia Gravis? (P05.172)

Objective: To determine if mycophenolate mofetil (MMF) can be tapered without worsening in patients with myasthenia gravis (MG). Background MMF is frequently used in the treatment of MG, but no studies address long term management. Design/Methods: The Duke MG Patient Database was reviewed to identify all patients who were prescribed MMF from 1999-2011. Two hundred fifty-seven patients with adequate data were identified and 147 reached Minimal Manifestation Status (MMS) or Pharmacologic Remission (PR) after starting MMF. Their records were reviewed to determine if a taper of MMF had been attempted and were analyzed for factors including initial and worst MGFA scores, duration of MG prior to starting MMF, MMF dose, and concurrent therapies. If MG symptoms recurred after the dose of MMF was tapered, the dose at which relapse occurred and the subsequent clinical course were recorded. Patients were required to be on a stable lower dose of MMF for 6 months for a taper to be deemed successful. Results: MMF taper or discontinuation was attempted in 60 of 147 patients. Forty-four attempts (73%) were successful. No significant differences were found between the taper success and failure groups, other than an increased rate of prednisone use in the relapsing group (42% vs 14%). In the sixteen patients who failed attempts at an MMF taper, most developed only ocular symptoms and 69% again achieved MMS or PR after the prior dose was restored. The mean dose at which relapse occurred was 1066 mg/day (mean starting dose 2375 mg/day). Only one patient required addition of therapy (prednisone). Conclusions: In this retrospective analysis, 73% of MG patients tolerated MMF dose reduction without worsening. Concurrent prednisone use was associated with a higher rate of taper failure. In patients who did relapse, their symptoms were minor and most improved after the prior dose was restored. Disclosure: Dr. Hobson-Webb has received personal compensation for activities with Frederick O9Connor Medical Consultants as a consultant.Dr. Hobson-Webb has received research support from Genzyme Corporation. Dr. Juel has nothing to disclose. Dr. Guptill has nothing to disclose. Dr. Massey has nothing to disclose. Dr. Sanders has received personal compensation for activities with Athena Diagnostics, Accordant Health Services, Jacobus Pharmaceuticals, CytoKinetics, Bayhill Therapeutics, and GlaxoSmithKline, Inc.

Mycophenolate Mofetil-Related Enterocolitis and Weight Loss: A Pediatric Case Series

Mycophenolate mofetil (MMF) is an immunosuppressive medication utilized in the management of both autoimmune and solid organ transplant patients. Diarrhea is a common gastrointestinal side effect of MMF, but more severe forms of GI symptoms are described in renal transplant patients with a distinct pattern of histopathologic change, similar to graft-versus-host disease or Crohn's disease. This rare entity, commonly referred to as “MMF-related enterocolitis,” has been described in adult patients, mostly in renal transplant patients, and in only two pediatric renal transplant patients. In previously reported cases, symptoms and abnormal histopathology improve with dose reduction of MMF. We describe a series of three pediatric patients with varied underlying disease process who presented with severe diarrhea and histopathologic findings characteristic of MMF-related enterocolitis, who share a novel finding of weight loss as a complication of MMF-related enterocolitis in pediatric patients.

Mycophenolic acid agents: is enteric coating the answer?

Correspondence: Matthew Cooper Division of Transplantation, University of Maryland School of Medicine, Baltimore, MD, USA Tel +1 410 328 7336 Fax +1 410 328 6343 email mcooper@smail.umaryland.edu Abstract: Addition of mycophenolate mofetil (MMF) to calcineurin-based immunosuppressive therapy has led to a significant improvement in graft survival and reduction of acute rejection in renal transplant recipients. However, in clinical practice, MMF dose reduction, interruption, or discontinuation due to hematological and gastrointestinal (GI) side-effects occurred in up to 50% of the patients. Large retrospective analyses have demonstrated that patients requiring MMF dose manipulation due to adverse events experienced a higher rate of rejection and graft loss. Enteric-coated mycophenolate sodium (EC-MPS) was developed with the goal of improving upper GI side-effects. Here, we review the efficacy and safety of EC-MPS in de novo kidney transplant recipient, and in stable renal transplant patients who were converted from MMF. The changes in GI-related adverse events using patient-reported outcome instruments are also reviewed.