Everolimus‐induced loss of wound strength can be prevented by a short postoperative delay in its administration

Willems, M.C.; Hendriks, T.; Man, Ben M. de; Lomme, Roger M. L. M.; Vliet, J. Adam van der

doi:10.1111/j.1524-475x.2011.00730.x

Cited by 7 publications

(4 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using this robust approach, the incidence and duration of wound healing complications at months one and three post‐transplant were found to be similar in the everolimus and MMF arms . Clinical data suggesting that the impairment of wound healing has declined as the intensity of mTOR inhibitor dosing has decreased are consistent with preclinical evidence demonstrating that the effect of mTOR inhibitor on experimental wound healing is dose dependent .…”

mentioning

confidence: 53%

Wound events in kidney transplant patients receiving de novo everolimus: a pooled analysis of three randomized controlled trials

Cooper

Wiseman

Zibari

et al. 2013

Clinical Transplantation

View full text Add to dashboard Cite

Data were pooled from three prospective, multicenter trials in which 1996 de novo kidney transplant recipients were randomized to everolimus 1.5 or 3.0 mg or mycophenolic acid (MPA), with cyclosporine and steroids. Wound healing complications reported as adverse events were retrospectively reviewed in a blinded manner. The incidence of wound healing adverse events was 17.6% (351 of 1996) by day 90 and was similar for everolimus 1.5 mg (16.6% [110 of 661]) vs. MPA (14.3% [95 of 665]) (p = 0.255), but higher with everolimus 3.0 mg (21.8% [146 of 670]) (p < 0.001 vs. MPA). Similar results were observed for wound healing complications reported as serious adverse events. The 12-month incidence of lymphocele was 11.2% with everolimus 1.5 mg and 8.9% with MPA (p = 0.171), but lymphocele reported as a serious adverse event were more frequent with everolimus 1.5 mg (6.5% vs. 3.5%; p = 0.012). The hazard ratio (HR) for any wound healing complication vs. MPA was not significantly higher for everolimus <3 ng/mL (HR 1.33; 95% CI 0.94-1.88; p = 0.104), but increased to 1.46 (95% CI 1.12-1.90; p = 0.005) for 3-8 ng/mL and 1.69 (95% CI 1.20-2.38; p = 0.002) for >8 ng/mL. These results suggest that de novo kidney transplant patients receiving an initial everolimus dose of 1.5 mg do not appear to have a pronounced increased risk of wound healing complications vs. patients receiving MPA.

show abstract

mentioning

confidence: 53%

Wound events in kidney transplant patients receiving de novo everolimus: a pooled analysis of three randomized controlled trials

Cooper

Wiseman

Zibari

et al. 2013

Clinical Transplantation

View full text Add to dashboard Cite

show abstract

“…Willems et al showed that loss of wound strength can be prevented by delaying postoperative administration of everolimus 87. In the study by Masetti et al, in which everolimus was initiated 10 days after transplantation, incisional hernias were reported more frequently in the everolimus group than with cyclosporine (46.1% versus.…”

Section: Everolimusmentioning

confidence: 99%

The role of everolimus in liver transplantation

Ganschow¹,

Pollok²,

Jankofsky³

et al. 2014

CEG

View full text Add to dashboard Cite

During the last 5 decades, liver transplantation has witnessed rapid development in terms of both technical and pharmacologic advances. Since their discovery, calcineurin inhibitors (CNIs) have remained the standard of care for immunosuppression therapy in liver transplantation, improving both patient and graft survival. However, adverse events, particularly posttransplant nephrotoxicity, associated with long-term CNI use have necessitated the development of alternate treatment approaches. These include combination therapy with a CNI and the inosine monophosphate dehydrogenase inhibitor mycophenolic acid and use of mammalian target of rapamycin (mTOR) inhibitors. Everolimus, a 40-O-(2-hydroxyethyl) derivative of mTOR inhibitor sirolimus, has a distinct pharmacokinetic profile. Several studies have assessed the role of everolimus in liver transplant recipients in combination with CNI reduction or as a CNI withdrawal strategy. The efficacy of everolimus-based immunosuppressive therapy has been demonstrated in both de novo and maintenance liver transplant recipients. A pivotal study in 719 de novo liver transplant recipients formed the basis of the recent approval of everolimus in combination with steroids and reduced-dose tacrolimus in liver transplantation. In this study, everolimus introduced at 30 days posttransplantation in combination with reduced-dose tacrolimus (exposure reduced by 39%) showed comparable efficacy (composite efficacy failure rate of treated biopsy-proven acute rejection, graft loss, or death) and achieved superior renal function as early as month 1 and maintained it over 2 years versus standard exposure tacrolimus. This review provides an overview of the efficacy and safety of everolimus-based regimens in liver transplantation in the de novo and maintenance settings, as well as in special populations such as patients with hepatocellular carcinoma recurrence, hepatitis C virus-positive patients, and pediatric transplant recipients. We also provide an overview of ongoing studies and discuss potential expansion of the role for everolimus in these settings.

show abstract

“…In case of a negative effect of MMF on wound strength, it will be interesting to find out if any persistence of the effect is measured when delaying MMF for 3 days, as we have measured in a different experiment with Everolimus, in the same bowel anastomosis model. 18 …”

mentioning

confidence: 99%

The Effect of Mycophenolate Mofetil on Early Wound Healing in a Rodent Model

Willems

Hendriks

Lomme

et al. 2016

Transplantation Direct

Self Cite

View full text Add to dashboard Cite

BackgroundImmunosuppressant agents are inevitable for solid organ recipients, but may have a negative effect on wound healing that is difficult to measure because of clinical use of a polydrug regime. The evidence on mycophenolate mofetil (MMF) is scarce and contradictory. This study aims to investigate the effect of MMF administration on wound healing.MethodsNinety-six male Wistar rats divided into 4 groups underwent anastomotic construction in ileum and colon at day 0. Three groups received daily oral doses of 20 or 40 mg/kg MMF or saline (control group) from day 0 until the end of the experiment. Half of each group was analyzed after 3 days and half after 7 days. Another group started the medication 3 days after the laparotomy and was analyzed after 7 days, half of this group received 20 mg/kg and half 40 mg/kg MMF. Wound strength in anastomoses and in the abdominal wall was measured using bursting pressure, breaking strength, and histology. Trough levels were measured.ResultsSignificant differences in wound strength were seen in ileum tissue after 3 days, which surprisingly showed a stronger anastomosis in the experimental groups. Bursting pressure as well as breaking strength was higher in the low-dose and high-dose MMF group compared with the control group. A negative effect was measured in abdominal wall tissue for the highest-dose group, which disappeared when the medication was delayed for 3 days. Histology showed poorer bridging of the submucosal layer and more polymorphonuclear cell infiltration in the ileum specimens of the control group compared with the treatment groups.ConclusionsAs a single agent in a preclinical wound healing model in the rat, MMF has no negative effect on healing of bowel anastomoses but might have a negative effect on the healing of abdominal wall.

show abstract

Everolimus‐induced loss of wound strength can be prevented by a short postoperative delay in its administration

Cited by 7 publications

References 32 publications

Wound events in kidney transplant patients receiving de novo everolimus: a pooled analysis of three randomized controlled trials

Wound events in kidney transplant patients receiving de novo everolimus: a pooled analysis of three randomized controlled trials

The role of everolimus in liver transplantation

The Effect of Mycophenolate Mofetil on Early Wound Healing in a Rodent Model

Contact Info

Product

Resources

About