Wound healing adverse events in kidney transplant recipients receiving everolimus with reduced calcineurin inhibitor exposure or current standard-of-care: insights from the 24-month TRANSFORM study

ABSTRACT

Objectives

In TRANSFORM, de novo kidney transplant recipients received either everolimus in combination with reduced-exposure calcineurin inhibitor (EVR+rCNI) at standard EVR pre-dose concentrations of 3–8 ng/mL or mycophenolic acid plus standard-exposure CNI (MPA+sCNI). The authors analyzed the incidence of wound healing adverse events (WHAEs) over the 2-year study period 15.

Methods

Patients were randomized to either EVR+rCNI or MPA+sCNI, both combined with induction therapy and steroids 19.

Results

The safety population consisted of 2,026 patients (EVR+rCNI: 1,014, MPA+sCNI: 1,012). The proportion of patients with at least 1 WHAE was comparable between EVR+rCNI and MPA+sCNI treatment groups [20.6% vs. 17.3%; risk ratio (RR): 1.19; 95% confidence interval (CI): 0.99, 1.43] at month 24. The numerical difference between EVR+rCNI and MPA+sCNI was mainly caused by an increased proportion of EVR patients with lymphocele and wound dehiscence [7.5% vs. 5.1% (RR: 1.46; 95% CI: 1.04, 2.05) and 3.9% vs. 1.8% (RR: 2.22; 95%CI: 1.28, 3.84), respectively] 20.

Conclusion

The immediate introduction of EVR+rCNI after kidney transplantation was associated with an overall comparable incidence of WHAEs versus current standard-of-care over the 24-month study period. There was an increased relative risk of experiencing lymphocele and wound dehiscence but the absolute risks were rather low in both groups 21.

CT.gov identifier

NCT01950819.

KEYWORDS:

• Calcineurin inhibitor
• everolimus
• kidney transplantation
• randomized
• safety
• wound healing

Acknowledgments

The manuscript was prepared with assistance from a professional medical writer (Edgar A. Mueller, 3P Consulting), funded by Novartis.

Authors’ contributions

All authors except Peter Bernhardt and Maria Pilar Hernandez Gutierrez participated in the performance of the research (i.e. they recruited patients, collected data and participated in data analysis/interpretation). Maria Pilar Hernandez Gutierrez provided statistical support. Peter Bernhardt provided medical input and was involved in designing the study. All authors critically reviewed the manuscript and approved the final version for publication.

Declaration of interest

F Citterio has received consulting honoraria and travel grants from Novartis, Astellas, Pfizer and Bristol Myers Squibb. M Henry has received consulting honoraria from Novartis. MP Hernandez Gutierrez and P Bernhardt are employees of Novartis. Y Watarai has received consulting honoraria and travel grants from Novartis, Astellas and Chugai Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

The TRANSFORM study was funded by Novartis Pharma AG, Basel, Switzerland. Medical writing support was funded by Novartis.