Renal Transplant Patients With Gastrointestinal Intolerability to Mycophenolate Mofetil: Conversion to Enteric-Coated Mycophenolate Sodium (original) (raw)
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Transplantation Proceedings, 2005
on behalf of the myPROMS LatAm Study Group ABSTRACT The immunosuppressant mycophenolate mofetil (MMF; CellCept) has greatly improved transplant recipients' clinical outcomes, but its efficacy may be limited by dose adjustments due to adverse events (AEs). An enteric-coated formulation of mycophenolate sodium (EC-MPS; myfortic), designed to improve gastrointestinal tolerability is now available. This Latin-American, prospective, multicenter, open-label, 6-month trial assessed the safety and tolerability of converting renal transplant recipients from MMF to EC-MPS. In total, 237 renal transplant recipients (stable Ն 3 months' posttransplant) receiving MMF (Յ1000 mg b.i.d.) were enrolled. Adults (n ϭ 218) were converted to EC-MPS 720 mg b.i.d. (equimolar to MMF 1000 mg b.i.d.) even if they were initially receiving Ͻ1000 mg MMF b.i.d. (ie, 47 adults received a higher than equimolar dose of EC-MPS). Children (n ϭ 19) were converted to EC-MPS 450 or 432 mg/m 2 b.i.d. Patients also received cyclosporine microemulsion (Neoral) and corticosteroids.
Transplantation Proceedings, 2011
Introduction. Enteric-coated mycophenolate sodium (EC-MPS) was developed to reduce the incidence of gastrointestinal adverse effects. This multicenter observational study was designed to evaluate the safety profile and drug tolerance in kidney transplant recipients. Methods. Three hundred adult kidney recipients (median age 48 years) were enrolled over 3 years to receive EC-MPS de novo (n ϭ 175), as a switch from azathioprine (n ϭ 62) or mycophenolate mofetil MMF (n ϭ 63); in combination with calcineurin inhibitor. Drug doses, serum creatinine, estimated glomerular filtration rate (eGFR), as well as drug tolerance, patient and physician evaluation of therapy (on a 4-point scale) were recorded at enrollment and followed over 28 weeks. We modeled the probability of the highest level (ie, best result) of the categorical outcome variable. Results. Two hundred seventy-three patients completed the study (91%). In the pooled study group (1) best drug tolerance was expected more frequently with tacrolimus versus cyclosporine (odds ratio [OR] 2.12, P Ͻ .05); (2) best physician evaluation, with earlier EC-MPS introduction (OR for 4-week delay: 0.99, P Ͻ .03) and higher eGFR (OR for 5 mL/min increase: 1.21, P Ͻ .01). Among the EC-MPS de novo administrations group: (1) best drug tolerance was expected more frequently with coadministered tacrolimus versus cyclosporine (OR 3.14, P Ͻ .02); (2) best patient evaluation, with higher eGFR (OR for 1 mL/min increase: 1.04, P Ͻ .04); and (3) best physician evaluation, with higher eGFR (OR for 1 mL/min increase: 1.04, P Ͻ .001) and earlier EC-MPS introduction (OR for 4-week delay: 0.99, P Ͻ .03). In the conversion from MMF to EC-MPS group: (1) best drug tolerance was expected less frequently with coadministered cyclosporine versus tacrolimus (OR 0.05, P Ͻ .04) and more frequently with younger recipients (OR .001, P Ͻ .04); (2) best physician evaluation was expected more frequently with lower EC-MPS dose (OR for 360-mg dose increase: 0.4, P Ͻ .01) and with higher eGFR (OR for 5 mL/min increase: 1.42, P Ͻ .002). Adverse events were reported among 49/300 patients (16 serious adverse events). Conclusions. EC-MPS was tolerated better by younger kidney recipients, when combined with tacrolimus versus cyclosporine, and when introduced earlier after transplantation. EC-MPS tolerance decreased gradually with renal function deterioration. A DJUNCTIVE THERAPY with mycophenolic acid (MPA) has been shown to reduce the rate of acute rejection episodes and graft loss following renal transplan-tation in adults. 1-4 Nowadays prodrugs containing MPA constitute a backbone of modern immunosuppression in kidney transplant recipients. The gastrointestinal (GI) side From the Departments ofTransplantation Medicine and Nephrology (J.G.
American Journal of Transplantation, 2004
on behalf of the ERL B301 Study Groups The introduction of mycophenolate mofetil (MMF) represented a major advance in transplant medicine, although optimal use may be limited by gastrointestinal (GI) side-effects. An enteric-coated formulation of mycophenolate sodium (EC-MPS; myfortic ® ) has been developed with the aim of improving the upper GI tolerability of mycophenolic acid. Therapeutic equivalence of EC-MPS (720 mg b.i.d.) and MMF (1000 mg MMF b.i.d.), with concomitant cyclosporine microemulsion (Neoral ® ) and corticosteroids, was assessed in 423 de novo kidney transplant patients recruited to a 12-month, double-blind study. Efficacy failure (biopsyproven acute rejection [BPAR], graft loss, death or loss to follow up) at 6 months (EC-MPS 25.8% vs. MMF 26.2%; 95% CI: [− −8.7, + +8.0]) demonstrated therapeutic equivalence. At 12 months, the incidence of BPAR, graft loss or death was 26.3% and 28.1%, and of BPAR alone was 22.5% and 24.3% for EC-MPS and MMF, respectively. Among those with BPAR, the incidence of severe acute rejection was 2.1% with EC-MPS and 9.8% with MMF (p = = ns). The safety profile and incidence of GI adverse events were similar for both groups. Within 12 months, 15.0% of EC-MPS patients and 19.5% of MMF patients required dose changes for GI adverse events (p = = ns). Enteric-coated-MPS 720 mg b.i.d. is therapeutically equivalent to MMF 1000 mg b.i.d. with a comparable safety profile.
Transplantation, 2011
Background. Two open-label studies demonstrated that conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) significantly reduces gastrointestinal (GI) symptom burden and improves GI-specific health-related quality of life. Using a randomized design, this study evaluated changes in GI symptoms and health-related quality of life in patients converted from MMF to EC-MPS versus patients who continued with MMF-based treatment. Methods. In this 4-week, multicenter, randomized, prospective, double-blind, parallel-group trial, renal transplant recipients with GI symptoms receiving MMF plus a calcineurin inhibitorϮcorticosteroids were randomized to an equimolar dose of EC-MPSϩMMF placebo or continue on their MMF-based regimenϩEC-MPS placebo. The primary efficacy outcome was a change from baseline in total Gastrointestinal Symptom Rating Scale score of a minimally important difference of more than or equal to 0.3. Results. Three hundred ninety-six patients (EC-MPS group: nϭ199; MMF group: nϭ197) were included. A greater proportion of EC-MPS patients (62%) reached the primary efficacy outcome compared with MMF patients (55%); however, the difference was not statistically significant (Pϭ0.15). EC-MPS patients had a significantly greater decrease in the Gastrointestinal Symptom Rating Scale indigestion syndrome dimension versus MMF patients. Within the subgroups of patients with diabetes, patients transplanted 6 to 12 months of study enrollment, and patients on steroids, a statistically significant greater proportion of EC-MPS versus MMF patients reached the primary efficacy outcome. Conclusions. Conversion from MMF to EC-MPS may be associated with improvements in presence and severity of GI symptoms, particularly in patients with indigestion, diabetes, on steroids, and in patients converted between 6 and 12 months posttransplantation.
Transplantation, 2007
Background. The benefit of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in terms of gastrointestinal symptom burden has been evaluated previously using patient-reported outcomes. However, data are lacking concerning the sustained effect of conversion over time, and the potential impact of concomitant calcineurin inhibitor. Methods. In this 3-month, prospective, multicenter, longitudinal, open-label trial, MMF-treated renal transplant patients with gastrointestinal symptoms receiving cyclosporine or tacrolimus were converted to equimolar doses of EC-MPS. Change in gastrointestinal symptom burden was evaluated using a validated Gastrointestinal Symptom Rating Scale (GSRS). Results. A significant improvement in GSRS score was observed from baseline (2.61, 95% CI 2.54-2.68) to month 1 (1.87, 95% CI 1.81-1.93) after conversion to EC-MPS and was sustained to month 3 (1.81, 95% CI 1.74-188; both PϽ0.0001 versus baseline). The mean change in overall GSRS score from baseline to month 1 was Ϫ0.74 overall (cyclosporine: Ϫ0.73 and tacrolimus: Ϫ0.74; all PϽ0.0001 versus baseline), with a slight further improvement (Ϫ0.79) at month 3 (cyclosporine: Ϫ0.82 and tacrolimus: Ϫ0.78; all PϽ0.0001 versus baseline). A significant improvement in GSRS subscale scores was also observed in the total population regardless of calcineurin inhibitor at month 1, sustained to month 3 (all PϽ0.0001 versus baseline). The improvement in GSRS score postconversion was similar in African-American and non-African-American patients, and in diabetic and nondiabetic patients. Conclusions. This exploratory study in 728 patients demonstrates that following conversion from MMF to EC-MPS, regardless of concomitant calcineurin inhibitor, GSRS is improved and sustained over 3 months.
Jornal Brasileiro de Nefrologia, 2015
Introduction: Mycophenolate mofetil (MMF), pro-drug mycophenolic acid (MPA) is an immunosuppressive effective in the prophylaxis of acute rejection, but associated with gastrointestinal adverse events. Mycophenolate sodium (MPS) with enteric coating was developed with intention of reducing such gastrointestinal adverse events associated with MPA. Objective: To evaluate the tolerability of EC-MPS and MMF in renal transplant recipients. Methods: Retrospective, multicenter study, included 1380 patients who underwent a transplant between 07/01/2004 and 31/07/2007 in 18 Brazilian centers. Results: 1380 patients enrolled, 702 received EC-MPS and 678 received MMF. The average age of patients was 42.3 years, 60% were male and 62.5% of Caucasian ethnicity. The incidence of events evaluated in the composite endpoint of efficacy was not different between groups at the end of 24 months followup (22.9% for EC-MPS to MMF versus 19.9%, p = 0.203). Patients treated with EC-MPS had a higher incidence of gastrointestinal adverse events compared to those treated with MMF (57.7% vs. 52.5%), but there was no statistical difference between groups. Viral infections were more frequent in the EC-MPS group (38.2%) compared with MMF (32.6%). There was no difference in mean tolerated dose after the first (1187 ± 344 vs. 1209 ± 426 mg, p = 0.294) and second year (1172.3 ± 347 mg vs. 1197.4 ± 430.6 mg, p = 0.241) after transplantation. Conclusion: There was no statistical difference in the incidence of acute rejection, delayed graft function
Transplantation Proceedings, 2009
Background. Enteric-coated mycophenolate sodium (EC-MPS) was developed as an alternative agent to mycophenolate mofetil (MMF), aimed at reduction of gastrointestinal (GI) complications. Methods. Seventy-four patients (mean age 42.3 years) switched from MMF to MPS were included in the study and followed-up for 3 months (Visit 0, Visit 2 after 1 month and Visit 3 after 3 months). The mean time from transplantation to switch was 3.7 years. During Visit 2 and 3 the following were recorded: impact of treatment change on the severity of GI symptoms (4 point scale: 1-worsening, 2-no change, 3-improvement, 4-resolution), EC-MPS tolerance, adverse events (AEs), patient compliance and physician satisfaction with treatment (4 point scale: 1-bad, 2-fair, 3-good, 4-very good). Results. Sixty-three patients completed the study (85.1%). EC-MPS dose ranged from 720 to 1440 mg. GI symptom severity score averaged at 3.41. Symptoms most commonly compelling a conversion were: abdominal pain, diarrhea, abdominal colic, nausea, anorexia and vomiting. Out of 175 complaints, 144 (82%) either improved or resolved, 5 (2.86%) aggravated, and 25 (14.86%) persisted. Patient compliance and mean physician satisfaction score averaged at 3.70 and 3.02 at Visit 3, respectively. 9 AEs (2 severe) were reported. Causal relationship with the medication was suspected in 5 cases (1 case of SAE). The most common AEs were: anemia, infection (including sepsis), GI symptoms (abdominal pain, diarrhea). Conclusions. The following was concluded in our study: (1) sodium mycophenolate is well tolerated; (2) after switching from MMF to EC-MPS, gastrointestinal symptoms alleviated; (3) EC-MPS is a safe medication, with a low adverse events rate.