Watelle L, Touré M, Lamour JM, Kemna MS, Spinner JA, Hoffman TM, Carlo WF, Ballweg JA, Greenway SC, Dallaire F. J Heart Lung Transplant. 2023 Aug;42(8):1074-1081. doi: 10.1016/j.healun.2023.02.1705.
Take home points:
- After heart transplantation, immunosuppression with a single immunosuppressive drug after the first year post-transplant was noninferior to standard therapy (≥2 immunosuppressive drugs)
- Based on this retrospective analysis, monotherapy was not associated with change in the incidence of rejection, infection, and malignancy, and even the development of Coronary Artery Vasculopathy.
Commentary from Dr. Manoj Gupta (New York City, NY, USA), chief section editor of Pediatric & Fetal Cardiology Journal Watch.
Introduction:
Heart transplantation (HT) requires lifelong immunosuppression to prevent organ rejection and enable allograft and patient survival. Traditionally, maintenance immunosuppression following HT has required at least 2 immunosuppressive drugs. However, anecdotally, many patients are successfully maintained on monotherapy (defined as taking only a single immunosuppressive drug) for varying durations. Patients may be placed on monotherapy because of immunosuppressive drugs side effects or complications (i.e., post-transplant lymphoproliferative disease, PTLD) or they are deemed to be at low immunological risk for rejection (i.e., neonatal transplantation).
To test this, the authors leveraged data from the Pediatric Heart Transplant Society (PHTS) to describe a cohort of pediatric heart transplant recipients on monotherapy and to assess graft failure and complication rates in patients on monotherapy compared to those on ≥2 immunosuppressive drugs.
Methods:
For the current study, we included patients with their first heart transplant before 18 years of age between 1999 and 2020 and who had ≥1 year of follow-up data available. The primary outcome was graft failure, a composite of death and retransplantation. Secondary outcomes were graft rejection, infection, malignancy, cardiac allograft vasculopathy (CAV) and need for dialysis.
Results
We identified 3493 heart transplant recipients from the PHTS database meeting our inclusion criteria and exclusion criteria. Patient demographics and baseline characteristics are summarized in Table 1. The median follow-up time post-transplant was 6.7 years (range: 1.3-20.5 years, IQR 4.5-10 years) for a total of 26,740 patient-years. There were 893 patients (25.6%) switched to monotherapy at least once during follow-up with the remaining 2600 patients on ≥2 ISDs for their entire follow-up. The median time on monotherapy was 2.8 years (IQR 1.1-5.9 years) for a total of 3824 patient-years on monotherapy. Patients on monotherapy were younger at the time of transplant (median 1.3 years vs 6.2 years) and were more likely to have undergone transplantation as a neonate (48/893 vs 37/2600 patients or 5.4% vs 1.4%). The most common underlying diagnoses leading to HT were cardiomyopathy (1857/3493 patients, 53.2%) and congenital heart disease (1530/3493 patients, 43.8%) without a clear difference in diagnosis between those ever on monotherapy and those never on monotherapy.
At 1-year post-transplant (i.e., the start of follow-up for the current analysis), there were 260/3493 patients (7.5%) already on monotherapy. This proportion steadily increased to peak at 23.9% at 12.4 years post-HT and then slightly decreases thereafter.
The agent most frequently used during monotherapy was tacrolimus (69.7%) followed by cyclosporine (26.5%). Sirolimus was rarely used as monotherapy (1.8%). Other agents (mycophenolate mofetil (MMF), steroids, azathioprine and everolimus) were each used < 1% for monotherapy.
Discussion
How much immunosuppression is necessary for an individual child after heart transplantation is an important question. The use of monotherapy may offer fewer episodes of infection and malignancy post-transplant once past the higher-risk period of rejection within the first year post transplant. In this study, we found that a sizeable proportion of patients are on a single immunosuppressive drug and, importantly, monotherapy appears to be noninferior to standard (≥2 immunosuppressive drugs) post-transplant immunotherapy for the primary outcome of death or retransplantation.
Conclusions
Our study suggests that for children switched to monotherapy after HT, immunosuppression with a single ISD after the first year post-transplant was noninferior to standard therapy (≥2 ISDs) for the outcomes of death or retransplantation in the medium-term. We also found that monotherapy was not associated with change in the incidence of rejection, infection and malignancy, and even the development of CAV. Our data suggest that the clinician’s decision to switch these patients to monotherapy was not detrimental.
