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Abatacept Rescue Therapy in Kidney Transplant Recipients: A Case Series of Five Patients

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Dear Editors, Abatacept, a cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin (CTLA4-Ig), is a subcutaneously administered immunosuppressive drug that selectively inhibits T-cell activation by blocking the CD28-CD80/86 costimulatory pathway. Abatacept is widely… Click to show full abstract

Dear Editors, Abatacept, a cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin (CTLA4-Ig), is a subcutaneously administered immunosuppressive drug that selectively inhibits T-cell activation by blocking the CD28-CD80/86 costimulatory pathway. Abatacept is widely used in rheumatology, especially in the treatment of rheumatoid arthritis (1). More recently, intravenously administered belatacept, another CTLA4-Ig, has shown better renal transplant (RT) survival results, improvement in long-term renal function, and less de novo donor-specific antibody (DSA) formation than a calcineurin inhibitor (CNI) regimen, either in induction therapy or after conversion from CNIs (2–4). However, to date, abatacept has been reported only exceptionally as maintenance treatment in patients who have undergone renal transplantation (5). This letter reports on our experience with CNI conversion to self-administered subcutaneous abatacept in five patients who benefited from RT for 1.5–84 months (Table 1). The initiation of CTLA4-Ig therapy was motivated by graft biopsy-confirmed CNI toxicity in four patients (P1, P2, P3, and P4) and varying concentrations of tacrolimus owing to severe gastroparesis (P5). Abatacept maintenance therapy was chosen due to difficult peripheral venous access or to avoid hospitalization in the context of the COVID-19 pandemic. All patients received a 125 mg subcutaneous injection of abatacept every week (6). The first injection was performed in Day Hospital for monitoring and injection education. Treatment with CNIs was progressively withdrawn over 1–3 months (7). All patients received prednisone 5 mg/day and mycophenolate mofetil (P1, P2, P4, and P5) or everolimus (P3). The mean follow-up after switching to abatacept was 13.6 months. In all patients, renal function was similar between baseline and the last follow-up (Table 1). We did not observe any transplant rejection or any appearance of or increase in DSAs, which were routinely screened every 3 months (screening and single antigen identification, One Lambda Thermo Fisher). Two patients developed CMV disease (P1 and P5). It is of note that P5 was not receiving any CMV prophylaxis. In P1, CMV infection was refractory to available antivirals (valganciclovir, foscarnet) and the discontinuation of abatacept. Treatment with maribavir for 8 weeks reduced the viral load to less than 2,000 IU/ml, and viral load remained stable with only azathioprine and prednisone. In addition, we observed better control of blood pressure in P2 and P3, allowing the cessation of some of the antihypertensive drugs. In RT recipients with CNI intolerance, conversion to belatacept is an effective and validated option. However, this treatment has logistical drawbacks due to its intravenous formulation and its nurse-supervised infusion for 30–60 min (8). In patients with rheumatoid arthritis, a fixed-dose SC administration of 125 mg weekly compared with the body-weight-based monthly IV administration of 10 mg/kg allowed to obtain therapeutic concentrations and similar clinical remission rates irrespective of baseline patient body mass index (6). *Correspondence: Charlotte Uro-Coste [email protected]

Keywords: five patients; abatacept rescue; therapy; rescue therapy; treatment; transplant

Journal Title: Transplant International
Year Published: 2022

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