Time to therapeutic tacrolimus levels and association with acute cellular rejection and de novo donor-specific antibody development in lung transplant recipients Corey Dinunno, PharmD; Christine Pham, PharmD; Brett Pierce, PharmD; Ahmad Goodarzi, MD; Simon W. Yau, MD; Jihad G. Youssef, MD; Duc T. Nguyen, MD, PhD; Edward A. Graviss, PhD, MPH; Howard J. Huang, MD PURPOSE
RESULTS
Tacrolimus (FK506) is standard of care for preventing rejection in lung transplant for maintenance immunosuppression. Both acute cellular rejection (ACR) and de novo donor-specific antibodies (dnDSAs) are strongly associated with development of chronic lung allograft dysfunction. The optimal time to therapeutic (TTT) FK506 level post-transplant has not been established, and a standardized dosing strategy for all patients in the immediate post-transplant period may be inappropriate. We evaluated whether TTT FK506 impacted ACR and dnDSA rates within 6 months of lung transplantation.
Median TTT was 7 days (IQR 5.0-10.0) in 222 patients. There was no difference in ACR [7.6% vs 9.7% (p=0.63)] or dnDSA [35% vs 44% (p=0.20)] between patients achieving therapeutic FK506 <7 days vs >7 days. Recipients therapeutic <7 days had a longer median time to dnDSA development (44 days vs 27 days, p=0.043). TTR at 1 month was longer in patients therapeutic <7 days (40% vs 28%, p<0.001). Neither median nor percentage of TTR had an impact on the composite outcome (HR 0.99; 95% CI 0.95-1.03). AKI incidence (>stage 2) was similar (40.3% vs 38.8%, p=0.82) between groups. Multivariate analysis identified receipt of a double lung transplant as the only covariate associated with a higher risk of AKI [OR 3.56, 95% CI 1.40-9.05 (p=0.01)].
METHODS
We retrospectively reviewed lung transplant recipients between 5/2016 – 12/2019. We excluded patients who did not receive FK506, received their first dose >48 hours post-transplant, were transitioned off FK506 during the study period, or expired within 30 days. Our primary outcome was a composite of ACR and dnDSA development within 6 months for patients achieving therapeutic FK506 (8-15 ng/mL) within 7 days, versus >7 days. Secondary endpoints included: time within therapeutic range (TTR) at 1 month and incidence of acute kidney injury (AKI) within 14 days.
CONCLUSION
There was no significant difference in development of ACR or dnDSA within 6 months between lung transplant recipients achieving therapeutic FK506 <7 days vs >7 days. Increased time to dnDSA development in the <7-day cohort suggests a potential benefit to minimizing time to therapeutic FK506 level post-transplantation.
PGY1 PHARMACY RESIDENCY
Corey Dinunno, PharmD Corey completed his undergraduate coursework and earned his PharmD from the University of Connecticut in 2020. After completion of his PGY1, Corey will be completing a PGY2 in Internal Medicine at Houston Methodist Hospital. Primary project preceptor: Christine Pham, PharmD Presented at 2020 Virtual Vizient Pharmacy Network Conference; 2021 Virtual Midwest Pharmacy Residents Conference; 2021 Virtual ISHLT Annual Meeting
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