CLINICAL OUTCOMES OF KIDNEY TRANSPLANT RECIPIENTS DURING TRANSITION FROM IMMUNOASSAY TO TANDEM MASS SPECTROMETRY BASED THERAPEUTIC DRUG MONITORING OF EVEROLIMUS

CLINICAL IMMUNOSUPPRESSION - KIDNEY EARLY

H.S. Yong¹, P.Y.W. Fan¹, P.H. Lee¹, W.Y. Ng², T. Kee^3
1Pharmacy, Singapore General Hospital, Singapore/SINGAPORE, ²Pathology, Singapore General Hospital, Singapore/SINGAPORE, ³Renal Medicine, Singapore General Hospital, Singapore/SINGAPORE

Body: Introduction: Blood levels of everolimus (ERL) measured by fluorescent polarization immunoassay (FPIA) have been shown to be higher than levels measured by tandem mass spectrometry (TMS). A pilot study at our hospital showed that target ERL trough levels of 3-8ng/mL measured by FPIA may have to be adjusted to a lower range of 2–7ng/mL if TMS is used instead because of cross-reactivity of the antibody used in FPIA with the ERL metabolite. As a result, we undertook a prospective study to determine the clinical impact of switching from FPIA to TMS based therapeutic drug monitoring (TDM) of ERL. Methods: This prospective study at our hospital included 18 kidney transplant recipients who were receiving ERL in combination with corticosteroids and either cyclosporine (ERL-CsA) (n=8) or a mycophenolate analogue (ERL-MPA) for maintenance immunosuppression (n=10). Prior to switching to TMS for TDM of ERL, baseline ERL trough levels at steady state measured by FPIA, baseline CsA trough levels and clinical parameters such as serum creatinine, full blood count, fasting lipid levels, urine protein-creatinine ratio, and infection rate were recorded. After switching to TMS, the same parameters were prospectively collected for a period of 3 months and compared with those obtained during FPIA-based TDM. An average of 12 sampling points was used for the collection of data for the respective parameters and was expressed as median in the study. The target trough levels for ERL and CsA for the ERL-CsA group were 3-8ng/mL and 25-50ng/mL respectively. For the ERL-MPA group, the target trough levels for ERL and MPA were 6-8ng/mL and 2-4ng/mL respectively. Results: There were no differences in the ERL levels measured using both FPIA and TMS in the ERL-MPA group. In contrast, the ERL levels obtained from TMS in the ERL-CsA group were significantly lower than those measured using FPIA. Nevertheless, no significant dose adjustments for ERL, CsA or MPA were made to either group after transition to TMS-based monitoring.There was no significant difference in patients’ clinical parameters when ERL levels was monitored using FPIA versus TMS. In addition, there was no increase in episodes of infection with use of TMS compared to FPIA for the monitoring of ERL.Clinical parameters during FPIA and TMS based TDM of ERL

Parameters expressed as median (ranges)	FPIA (n=18)	TMS (n=18)	p value
Everolimus trough levels (ng/mL) with concomitant CsA with concomitant MPA	5.1(4.3-6.3) 6.1(5.3-7.9)	3.8(2.0-4.1) 5.3(3.5-9.1)	0.03 0.69
Cyclosporine levels (ng/mL)	38 (25-78)	30 (25-54)	0.45
Everolimus dose (mg/day)	1.5(1.0-2.5)	1.5(1.0-2.5)	1.00
Cyclosporine dose (mg/day)	60 (30-100)	60 (30-100)	1.00
Mycophenolate mofetil dose (mg/day)	750 (250-1250)	500 (250-1250)	0.50
Prednisolone dose (mg/day)	10 (10-20)	10 (9-10)	0.25
Serum creatinine (umol/L) at month 1 at month 2 at month 3	124(88-256) 160(84-279) 150(73-276)	134(85-251) 139(79-321) 146(80-258)	0.73 1.00 0.75
Calculated glomerular filtration rate (ml/min) at month 1 at month 2 at month 3	53 (22-83) 39 (23-74) 39 (20-75)	38 (24-68) 39 (17-79) 38 (24-69)	1.00 1.00 0.75
Urine protein-creatinine ratio (g/g)	0.16 (0-0.47)	0.13 (0-0.73)	0.75
Total cholesterol (mmol/L)	5.5 (2.3-8.3)	5.4 (4.4-6.6)	0.75
Triglyceride (mmol/L)	1.4 (0.9-2.6)	1.4 (0.8-4.0)	0.34
Low density lipoprotein (mmol/L)	2.9 (2.6-4.3)	3.0 (1.9-4.0)	1.00
Hemoglobin (g/dL)	12.8 (10.1-17.1)	12.7 (8.2-16.1)	1.00
White blood count (109/L)	7.4 (3.8-16.0)	8.0 (4.2-16.4)	0.82
Platelet count (109/L)	245 (137-486)	270 (145-483)	0.24
Infection episodes	0	1	-

Conclusion: Although there was a trend towards lower ERL levels with use of TMS especially in the ERL-CsA group, there were no observable differences in the clinical outcomes with the difference in levels documented. Therefore the transition from FPIA to TMS based TDM for ERL does not require pre-emptive dosage adjustments for ERL or additional monitoring for patients.

Disclosure: All authors have declared no conflicts of interest.