Comparative analysis of adverse events requiring suspension of mTOR inhibitors: everolimus versus sirolimus.
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.
Department of Nephrology, Hospital Clínico San Carlos, Madrid, Spain. sanchezfruct@telefonica.net
A I
AI
Sánchez-Fructuoso
J C
JC
Ruiz
I
I
Pérez-Flores
C
C
Gómez Alamillo
N
N
Calvo Romero
M
M
Arias
D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016030:Kidney Transplantation; D020123:Sirolimus / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
D007166:Immunosuppressive Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus