ABSTRACT
Rationale: Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator therapy has previously been contraindicated in solid organ transplant recipients. This was due to lack of data and concern for interaction with immunosuppressive drug regimens. However, in post-lung transplant recipients, CFTR modulators may improve extra-pulmonary manifestations of cystic fibrosis without impacting graft function or drug levels. Herein, we present our single center experience with the use of Trikafta in post-lung transplant recipients.Methods: We retrospectively analyzed the charts of 9 lung transplant recipients who were started on Trikafta since December of 2019. Trikafta was started in patients with poorly controlled CF-related diabetes, sinus issues, significant GI manifestations, or inability to gain weight. We assessed graft function utilizing ISHLT staging, immunosuppressive drug dosing before and after starting Trikafta, any reported side effects, white blood cell (WBC) count, weight, blood sugar monitoring, sinus and GI symptoms, and need for surgical intervention.Results: Trikafta was initiated a mean of 1,249.6 days post-transplant. Of the 9 patients, 5 were female and 4 were male. 1 patient died due to complications of COVID ARDS and 1 patient underwent retransplantation, at which time Trikafta was stopped. All patients had stable or increased graft function except for 2;one of which underwent retransplantation and the second was relisted for retransplantation. All patients were treated with tacrolimus with only one requiring significant dose adjustment. 1 patient experienced joint pain for which Trikafta dosing was reduced and another patient experienced abdominal pain for which Trikafta was stopped, with plans to re-introduce at a lower dose. WBC remained stable in all patients. 50% of people gained weight with mean change of 5.2lbs. One patient was able to stop insulin usage completely with the remainder having stable blood sugar levels. Sinus symptoms were reported to have improved in 8/9 patients. Complains of GI symptoms including gastroparesis, fullness, bloating and reflux improved in all patients. No patient underwent surgical intervention for GI or sinus complications after initiation of Trikafta. Conclusion: Our single center experience revealed that Trikafta did not impact graft function or cause significant drug to drug interactions with immunosuppressive regimens. Our patients tolerated Trikafta well without significant side effects and half gained weight. GI and sinus symptoms improved in the majority of our patients without the need for any surgical intervention.
ABSTRACT
COVID-19 is the disease caused by SARS-CoV-2 that portends both a relatively high mortality rate as well as high rate of intensive care admission amongst all age groups; however effective therapy remains poorly characterized. Post-transplant patients are especially high risk and underrepresented in the literature. In these patients, cytokine release may play a significant role in the development of acute respiratory distress syndrome, raising the hypothesis that interleukin-6 inhibitors such as tocilizumab may be of benefit. Here, we describe two high-risk post-transplant patients who were treated with single-dose tocilizumab after intubation for moderate acute respiratory distress syndrome secondary to confirmed COVID-19 infection. Both patients recovered rapidly and were successfully extubated and discharged from the hospital without need for supplemental oxygen shortly thereafter, and their clinical improvement correlated with response in interleukin-6 levels. Tocilizumab appears to hold promise for critically ill COVID-19 patients who require mechanical ventilation when given shortly after intubation.