Background
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.
Objectives
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.
Methods
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.
Results
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).
Conclusions
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.
Condensed abstract
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.
KEYWORDS
Abbreviations:
HT (heart transplantation), ISD (immunosuppressive drug), PTSD (post-transplant lymphoproliferative disease), PHTS (Pediatric Heart Transplant Society), CAV (coronary artery vasculopathy), MMF (mycophenolate Mofetil)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: March 03, 2023
Publication stage
In Press Journal Pre-ProofIdentification
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