Comparison of tacrolimus plus induction via intraoperative single high-dose of rabbit anti-T-lymphocyte globulins versus tacrolimus monotherapy in adult liver transplantation: 1-year results of an investigator-driven randomized controlled trial

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Kevin Ackenine(1), Samuele Iesari1, (2), Maxime Foguenne(1), Chantal De Reyck(1), Eliano Bonaccorsi Riani(1), Olga Ciccarelli(1), Laurent Coubeau(1), Quirino Lai(3), Mina Komuta(4), Pierre Gianello(5), Jan Lerut(1) Published in the journal : July 2018 Category : Mémoires de Recherche Clinique

Summary :

BACKGROUND

The efficacy of anti-lymphocyte serum (ALS) induction remains inconclusive in liver transplantation (LT) due to poorly designed trials.

 

OBJECTIVE

To determine whether induction with ALS is superior to no induction in adult LT.

 

STUDY DESIGN

Randomized controlled trial including 206 adults (aged >15 years) and comparing tacrolimus monotherapy (TAC, n=109) versus tacrolimus plus intraoperative single high-dose (9 mg/kg) of rabbit anti-T-lymphocyte globulins (ATLG; n=97). All patients underwent similar follow-up, including biopsies scored according to the Banff classification. Graft rejection was considered clinically relevant and treated if pathologic and biochemical changes were consistent. The primary endpoint was minimization of immunosuppression to monotherapy; secondary endpoints included biopsy-proven rejection, clinical rejection, as well as patient (PS) and graft (GS) survival.

 

RESULTS

At 1 year, 79 (96.3%) of the 81 ATLG patients and 101 (99.0%) of the 102 TAC patients were steroid-free (p=0.585); 28 (34.6%) ATLG and 31 (30.4%) TAC patients were on double-therapy immunosuppression (p=0.633). One-year PS and GS of ATLG and TAC patients were 84% and 92% (p=0.260) and 76% and 90% (p=0.054), respectively. Though there were significantly fewer moderate-to-severe rejections (Banff 6-9) on Day 7 in the ATLG group than in the TAC group (10.0% vs. 24.0%, p=0.019), the cumulative proportion of patients experiencing clinically relevant rejection (16.5% ATLG vs. 22.0% TAC, p=0.379), steroid-sensitive rejection (13.4% ATLG vs. 17.4% TAC, p=0.448), steroid-resistant rejection (2.1% ATLG vs. 3.7% TAC, p=0.686), and chronic rejection (1.0% ATLG vs. 0.9% TAC, p=1.000) was similar in both groups.

 

CONCLUSIONS

ATLG induction did not significantly impact immunosuppressive load, treated rejection, PS, and GS at 1 year following LT. Long-term results are required to assess the possible benefits of ATLG on immunosuppressive load and tolerance induction.