Steroid-free maintenance immunosuppression or calcineurin inhibi­tor minimization compared to standard quadruple immune­sup­pres­sion in kidney transplantation Interim analysis of the ALLEGRO trial

---

M.S. van Sandwijk, A.P.J. de Vries, S.J Bakker, I.J.M. ten Berge, S.P. Berger, H.J.W. de Fijter, J.J. Homan van der Heide, M.M. Idu, C. Krikke, K.A.M.I van Donselaar-van der Pant, M.E.J. Reinders, J. Ringers, N.C van der Weerd, F.J. Bemelman, J.S.F Sanders

Chair(s): dr. Michiel G.H. Betjes, internist-nefroloog, Erasmus MC & dr. Erik A.M. Verschuuren, internist-klinisch immunoloog, UMCG

Wednesday 9 march 2016

15:00 - 15:10h at Theaterzaal

Categories: Plenaire sessie

Parallel session: Plenaire sessie III - Healthy ageing: Word je gezond oud na een orgaan-transplantatie?

---

Background:
The determination of the immunosuppressive regimen delivering maximum efficacy with minimal toxicity in kidney transplant recipients is a continuing challenge.

Methods:
In this multicenter, investigator-driven, open-label trial, 295 kidney transplant recipients with a low to intermediate immunological risk were randomized to (1) standard triple maintenance immunosuppression (prednisolone, mycophenolic acid and tacrolimus after basiliximab and methylprednisolone induction) versus (2) steroid‑free maintenance immunosuppression or (3) calcineurin inhibitor minimization after six months. The primary endpoint was kidney function, measured as MDRD, creatinine clearance and proteinuria. Secondary endpoints included death, primary nonfunction, graft failure, biopsy proven rejections, discontinuation of study medication for more than six weeks, serious adverse events and cardiovascular risk factors (blood pressure, lipid profile and diabetes). In addition, a composite endpoint reflecting treatment failure, i.e. death, graft loss, rejection and discontinuation of study medication for more than six weeks was defined. The total study duration was two years, with a prespecified interim analysis at six months.

Results:
In this interim analysis, there were no differences in MDRD (43.2 vs 45.0 ml/min/1.73m²), creatinine clearance (58.5 vs 58.3 ml/min) or proteinuria (0.20 vs 0.19 g/day) between the corticosteroid withdrawal (CSWD) group and the chronic corticosteroid therapy (CCS) group. This was true for all donor subtypes (living, DBD and DCD). There were also no significant differences in the individual secondary outcomes of death (1.0 in the CSWD vs 1.5% in the CCS group), primary nonfunction (4.1% vs 1.5%), graft failure (3.1% vs 1.5%), rejection (18.6% vs 14.1%), type of rejection and discontinuation of study medication (19.6% vs 12.6%). Treatment failure occurred more often in the CSWD group (hazard ratio 1.65, p = 0.027), but this group experienced fewer serious adverse events (44 vs 57 per 100 patients, p = 0.048) due to a lower rate of infections. The cardiovascular profile in the CSWD group was also more favorable, with an improved diastolic blood pressure and an improved lipid profile.

Conclusion:
Steroid-free maintenance immunosuppression is a safe option for low to intermediate risk living, DBD and DCD kidney transplant recipients.