BACKGROUND: Inhibitors of mammalian target of rapamycin (mTORi) have been suggested as an alternative to calcineurin inhibitors (CNIs) to treat stable renal transplant recipients. However, their use has been significantly limited owing to a high incidence of side effects. OBJECTIVE: To compare the rate of dropout (mTORi elimination and CNI reintroduction) caused by side effects among renal transplant patients converted to everolimus (EVL) or sirolimus (SRL). METHODS: Between October 1999 and February 2010, 409 subjects were converted to an mTORi at least 3 months after transplantation, including 220 (53.8%) to EVL and 189 (46.2%) to SRL. Most patients were under CNI therapy. Patients were followed for a median of 35 months (interquartile range [IQR], 18-50 months). RESULTS: mTORi treatment was prematurely eliminated due to adverse events in 112 patients. The median time between the initiation of mTORi and discontinuation was 5.7 months (IQR, 1.9-15.7 months; range, 0.2-48 months): 5.5 (IQR, 1.6-16.3) in the EVL group and 7.4 (IQR, 2.6-15.6) in the SRL group. In the EVL group, the drug was stopped in 69 patients (31.4%), and in the SRL group in 43 patients (22.8%; P=.051). The most important causes of discontinuation were severe infections (2.3% in EVL group and 4.8% in SRL group; P=.17), pneumonitis (6.8 % in EVL group and 4.8 in SRL group; P=.38), acute rejection episode (4.1% in EVL group and 1.6% in SRL group; P=.13), proteinuria (4.1% in EVL group and 1.6% in SRL group; P=.13), renal function deterioration (2.3% in EVL group and 2.1% in SRL group; P=.91), and severe dermal eruption (2.3% in EVL group and 0.5% in SRL group; P=.14). CONCLUSIONS: Although the overall incidence discontinuations due to side effects was higher in the EVL group, there was no greater frequency of severe side effects, such as pneumonitis, proteinuria, acute rejection episodes, renal function deterioration, or dermal eruptions.
BACKGROUND: Inhibitors of mammalian target of rapamycin (mTORi) have been suggested as an alternative to calcineurin inhibitors (CNIs) to treat stable renal transplant recipients. However, their use has been significantly limited owing to a high incidence of side effects. OBJECTIVE: To compare the rate of dropout (mTORi elimination and CNI reintroduction) caused by side effects among renal transplant patients converted to everolimus (EVL) or sirolimus (SRL). METHODS: Between October 1999 and February 2010, 409 subjects were converted to an mTORi at least 3 months after transplantation, including 220 (53.8%) to EVL and 189 (46.2%) to SRL. Most patients were under CNI therapy. Patients were followed for a median of 35 months (interquartile range [IQR], 18-50 months). RESULTS: mTORi treatment was prematurely eliminated due to adverse events in 112 patients. The median time between the initiation of mTORi and discontinuation was 5.7 months (IQR, 1.9-15.7 months; range, 0.2-48 months): 5.5 (IQR, 1.6-16.3) in the EVL group and 7.4 (IQR, 2.6-15.6) in the SRL group. In the EVL group, the drug was stopped in 69 patients (31.4%), and in the SRL group in 43 patients (22.8%; P=.051). The most important causes of discontinuation were severe infections (2.3% in EVL group and 4.8% in SRL group; P=.17), pneumonitis (6.8 % in EVL group and 4.8 in SRL group; P=.38), acute rejection episode (4.1% in EVL group and 1.6% in SRL group; P=.13), proteinuria (4.1% in EVL group and 1.6% in SRL group; P=.13), renal function deterioration (2.3% in EVL group and 2.1% in SRL group; P=.91), and severe dermal eruption (2.3% in EVL group and 0.5% in SRL group; P=.14). CONCLUSIONS: Although the overall incidence discontinuations due to side effects was higher in the EVL group, there was no greater frequency of severe side effects, such as pneumonitis, proteinuria, acute rejection episodes, renal function deterioration, or dermal eruptions.
Authors: S Mielke; M Lutz; J Schmidhuber; M Kapp; D Ditz; J Ammer; H Einsele; G U Grigoleit; E Holler; D Wolff Journal: Bone Marrow Transplant Date: 2014-08-04 Impact factor: 5.483
Authors: Laurent M Willems; Felix Rosenow; Susanne Schubert-Bast; Gerhard Kurlemann; Johann Philipp Zöllner; Thomas Bast; Astrid Bertsche; Ulrich Bettendorf; Daniel Ebrahimi-Fakhari; Janina Grau; Andreas Hahn; Hans Hartmann; Christoph Hertzberg; Frauke Hornemann; Ilka Immisch; Julia Jacobs; Karl Martin Klein; Kerstin A Klotz; Gerhard Kluger; Susanne Knake; Markus Knuf; Klaus Marquard; Thomas Mayer; Sascha Meyer; Hiltrud Muhle; Karen Müller-Schlüter; Felix von Podewils; Susanne Ruf; Matthias Sauter; Hannah Schäfer; Jan-Ulrich Schlump; Steffen Syrbe; Charlotte Thiels; Regina Trollmann; Adelheid Wiemer-Kruel; Bernd Wilken; Bianca Zukunft; Adam Strzelczyk Journal: CNS Drugs Date: 2021-07-17 Impact factor: 5.749