Safety and efficacy of everolimus in maintenance kidney transplant patients: A 2-year post-marketing surveillance study in Japan
Yoko Watanabe1, Naomi Hayase2, Mariko Yamada3, Shuhei Kaneko4.
1Immunology, Hepatology & Dermatology Clinical Development Department, Novartis Pharma K.K. Japan, Tokyo, Japan; 2Medical Division, Novartis Pharma K.K. Japan, Tokyo, Japan; 3Patient Safety Japan Re-Examination Department, Novartis Pharma K.K. Japan, Tokyo, Japan; 4Biostatistics Pharma, Integrated Biostatistics Japan, Clinical Development & Analytics , Novartis Pharma K.K. Japan, Tokyo, Japan
On behalf of JP01 Study Group.
Background: A 2-year, observational, post-marketing surveillance (PMS) was conducted to assess safety and efficacy of everolimus (EVR) and explore renal impairment factors in maintenance of adult kidney transplant recipients (KTRs).
Method: This multicenter PMS study was conducted across 34 medical institutes in Japan. A total of 263 adult KTRs, treated with EVR during the surveillance period, were enrolled. Patients started EVR at various time points after transplant, and electronic data at Month 6, Years 1 and 2 after starting EVR treatment were collected.
Results: Of 263 KTRs, males accounted for 61.98%. The mean (±SD) age was 51.5 (±13.1) years. Renal function aggravation (31.56%), malignancy (13.69%) and arteriosclerosis (11.03%) were the major reasons for initiating EVR. The mean daily doses of cyclosporine and tacrolimus were reduced to ~72% and ~87% of the initial dose one month after EVR initiation and ~64% and ~79% at Year 2. The overall incidence of severe adverse events (SAEs) and adverse drug reactions (ADRs) were 15.97% and 49.43%, respectively. The most common ADRs were stomatitis (15.97%), proteinuria (9.89%), hyperlipidemia (5.32%), and peripheral edema (3.80%). The overall patient survival rate was 99.24% (261/263, <65 years: 100% and ≥65 years: 96.43%) and graft survival rate was 95.82% (252/263, 69.57% in patients with mean estimated glomerular filtration rate (eGFR [MDRD]) <30 mL/min/1.73m2; P<0.0001, and 84.21% in patients with urinary protein/creatinine ratio ≥0.55g/gCr). Graft loss and rejection were reported in 11 (6.84%) and in 18 (4.18%) of 263 patients throughout the efficacy analysis period, respectively. The eGFR values were stable (>55 mL/min/1.73m2) throughout the observation period. The examination of different renal impairment factors suggested that low eGFR, patients and donors age at baseline were associated with the subsequent decrease in renal function.
Conclusions: This is the first real world study of EVR in Japanese KTRs in maintenance phase. The majority of the patients on EVR were able to reduce the dose of calcineurin Inhibitors, and stable renal function with tolerable safety was observed throughout the study period.
The study was funded by Novartis Pharma K.K., Japan.
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