Standard immunosuppression for pediatric heart transplant recipients includes at least
two immunosuppressive drugs (ISDs). Some patients are maintained on a single ISD if
they have suffered complications or adverse drug reactions, but the outcomes of these
patients have not been systematically studied. Our aim was to determine whether patients
on a single ISD have equivalent graft survival (non-inferior hypothesis of a hazard
ratio (HR) < 1.1) compared to those on ≥2 ISDs.
METHODS AND RESULTS
For this retrospective, observational cohort study, we used the Pediatric Heart Transplant
Society dataset (1999-2019). We assessed outcomes in a cohort of consecutive patients
< 18 years of age on a single ISD after the first year post-transplant compared to
patients on ≥2 ISDs. Re-transplanted children were excluded. The primary outcome was
a composite of death or retransplantation (i.e., graft survival). Secondary outcome
measures included treated rejection, coronary artery vasculopathy (CAV), malignancy
and infection. Cox proportional models were used to assess survival after adjustments
for baseline risk factors. We used a time-to-event analysis that accounted for changes
in therapy and post-transplant lymphoproliferative disease (PTLD) status over time.
Our analysis included 2,605 heart transplant recipients (median follow-up time of
5.7 years, total of 23,255 patient-years). Of these, 888 (34%) were on a single ISD
for a median of 4.2 years, and 458 (18%) patients died or were retransplanted at a
median of 4.8 years post-transplant. Patients on a single ISD were younger at transplant
and more likely to have myocarditis at listing. Compared to patients on ≥2 ISDs, patients
on a single ISD had improved graft survival (HR 0.70 CI 0.52-0.94). Patients without
PTLD on a single ISD also had improved graft survival (HR 0.61 CI 0.45-0.84). For
patients with PTLD, we found improved graft survival, but lacked power to prove non-inferiority
(HR 0.58 CI 0.29-1.16). Being on a single ISD was associated with a decreased rate
of CAV (HR 0.58 CI 0.46-0.75), but was not associated with increased rates of infection,
rejection or malignancy.
Use of immunosuppressive therapy with a single ISD beyond the first year post-heart
transplant in children was associated with medium-term outcomes that were equivalent
or improved compared to children on more than a single agent. Whether monotherapy
would be effective as a first-line treatment in carefully selected patients and would
be sufficient longer term requires further study.