Single-drug immunosuppression is associated with noninferior medium-term survival in pediatric heart transplant recipients

Abstract

Patients are usually maintained on at least 2 immunosuppressive drugs (ISDs) after the first year post heart transplant. Anecdotally, some children are switched to single-drug monotherapy (a single ISD) for various reasons and varying durations. Outcomes associated with differences in immunosuppression after heart transplantation are unknown for children. A priori we defined a noninferiority hypothesis for monotherapy compared to ≥2 ISDs. The primary outcome was graft failure, a composite of death and retransplantation. Secondary outcomes included rejection, infection, malignancy, cardiac allograft vasculopathy and dialysis. This international, multicenter, retrospective, observational cohort study used data from the Pediatric Heart Transplant Society. We included patients who underwent first-time heart transplant <18 years of age between 1999 and 2020 with ≥1 year of follow-up data available. Our analysis included 3493 patients with a median time post-transplant of 6.7 years. There were 893 patients (25.6%) switched to monotherapy at least once with the remaining 2600 patients always on ≥2 ISDs. The median time on monotherapy after the first year post-transplant was 2.8 years (range 1.1-5.9 years). We found an adjusted hazard ratio (HR) of 0.65 (95%CI: 0.47-0.88) favoring monotherapy compared to ≥2 ISDs (p=0.002). There were no meaningful differences in the incidence of secondary outcomes between groups, except for a lower rate of cardiac allograft vasculopathy in patients on monotherapy (HR 0.58, 95%CI: 0.45-0.74). For pediatric heart transplant recipients placed on monotherapy, immunosuppression with a single ISD after the first year post-transplant was noninferior to standard therapy with ≥2 ISDs in the medium term. Some children are switched to a single immunosuppressive drug (ISD) for various reasons after heart transplant, but outcomes associated with differences in immunosuppression are unknown for children. We assessed graft failure in children on a single ISD (monotherapy) compared to ≥2 ISDs in a cohort of 3493 children with a first heart transplant. We found an adjusted hazard ratio of 0.65 (95%CI: 0.47-0.88) favoring monotherapy. We concluded that for pediatric heart transplant recipients placed on monotherapy, immunosuppression with a single ISD after the first year post-transplant was non-inferior to standard therapy with ≥2 ISDs in the medium term.