Adaptative Strategy of Immunosuppressive Drugs Dosage Adjustments When Combined With Nirmatrelvir/Ritonavir in Solid Organ Transplant Recipients With COVID-19

Nirmatrelvir/ritonavir is a promising option for preventing severe COVID-19 in solid organ transplant recipients with SARS-CoV-2 infection. However, concerns have arisen regarding potential drug interactions with calcineurin inhibitors (CNI). This two-phase multicentre retrospective study, involving 113 patients on tacrolimus and 13 on cyclosporine A, aimed to assess the feasibility and outcomes of recommendations issued by The French societies of transplantation (SFT) and pharmacology (SFPT) for CNI management in this context. The study first evaluated adherence to recommendations, CNI exposure, and clinical outcomes. Notably, 96.5% of patients on tacrolimus adhered to the recommendations, maintaining stable tacrolimus trough concentrations (C0) during nirmatrelvir/ritonavir treatment. After reintroduction, most patients experienced increased C0, with 42.9% surpassing 15 ng/mL, including three patients exceeding 40 ng/mL. Similar trends were observed in cyclosporine A patients, with no COVID-19-related hospitalizations. Moreover, data from 22 patients were used to refine the reintroduction strategy. Modelling analyses suggested reintroducing tacrolimus at 50% of the initial dose on day 8, and then at 100% from day 9 as the optimal approach. In conclusion, the current strategy effectively maintains consistent tacrolimus exposure during nirmatrelvir/ritonavir treatment, and a stepwise reintroduction of tacrolimus may be better suited to the low CYP3A recovery

Nirmatrelvir-ritonavir chez les patients greffés rénaux infectés par le SARS-CoV-2 : l’expérience d’une cohorte belge

INTRODUCTION: Le nirmatrelvir-ritonavir (NR) a démontré son efficacité et sa sécurité pour prévenir la survenue de formes sévères de COVID-19 chez les patients à risque de progression. Néanmoins, peu de données existent chez les greffés rénaux. De plus, le ritonavir interagit avec de nombreux médicaments, notamment avec les inhibiteurs de la calcineurine (IC). DESCRIPTION: Nous avons inclus dans cette étude monocentrique rétrospective tous les patients traités par NR entre le 28/04/2022 et le 03/06/2022. MÉTHODES: Le traitement par NR était de 5 jours (jour 1 à jour 5) à la dose recommandée. Le traitement usuel (notamment immunosuppresseur) était adapté selon les recommandations de la Société Française de Pharmacologie et Thérapeutiques. Un suivi standardisé biologique et clinique a été réalisé. RÉSULTATS: Quatorze patients ont été inclus (Tableau 1). Comparées à celles du jour 0 (veille de l’initiation du NR), les concentrations médianes de créatinine plasmatique et les charges virales de SARS-CoV-2 au jour 7 étaient respectivement similaires (p = 0,866) et fortement diminuées (p = 0,002). Deux patients ont eu une insuffisance rénale aigue rapidement résolutive dans un contexte de diarrhée et de sepsis urinaire. Les concentrations résiduelles d’IC sont restées relativement stables avec néanmoins 5 patients qui ont présenté des taux supra-thérapeutiques au premier dosage post reprise de l’IC. Après un suivi médian de 34 jours, aucun patient n’est mort ni n’a présenté de pneumonie virale. Deux patients ont dû être hospitalisés pour sepsis urinaire (au jour 2 et 11). Nous avons néanmoins observé 2 cas de récidive précoce de symptômes associée à une réaugmentation de la charge virale après traitement par NR (au jour 10 et 21). CONCLUSION: L’utilisation du NR est possible chez les greffés rénaux sous condition d’un respect strict des adaptations thérapeutiques recommandées. 14 % de la cohorte a présenté une récidive précoce en cours d’investigation

Adaptative Strategy of Immunosuppressive Drugs Dosage Adjustments When Combined With Nirmatrelvir/Ritonavir in Solid Organ Transplant Recipients With COVID-19

International audienceNirmatrelvir/ritonavir is a promising option for preventing severe COVID-19 in solid organ transplant recipients with SARS-CoV-2 infection. However, concerns have arisen regarding potential drug interactions with calcineurin inhibitors (CNI). This two-phase multicentre retrospective study, involving 113 patients on tacrolimus and 13 on cyclosporine A, aimed to assess the feasibility and outcomes of recommendations issued by The French societies of transplantation (SFT) and pharmacology (SFPT) for CNI management in this context. The study first evaluated adherence to recommendations, CNI exposure, and clinical outcomes. Notably, 96.5% of patients on tacrolimus adhered to the recommendations, maintaining stable tacrolimus trough concentrations (C 0 ) during nirmatrelvir/ritonavir treatment. After reintroduction, most patients experienced increased C 0 , with 42.9% surpassing 15 ng/mL, including three patients exceeding 40 ng/mL. Similar trends were observed in cyclosporine A patients, with no COVID-19-related hospitalizations. Moreover, data from 22 patients were used to refine the reintroduction strategy. Modelling analyses suggested reintroducing tacrolimus at 50% of the initial dose on day 8, and then at 100% from day 9 as the optimal approach. In conclusion, the current strategy effectively maintains consistent tacrolimus exposure during nirmatrelvir/ritonavir treatment, and a stepwise reintroduction of tacrolimus may be better suited to the low CYP3A recovery

Adaptative Strategy of Immunosuppressive Drugs Dosage Adjustments When Combined With Nirmatrelvir/Ritonavir in Solid Organ Transplant Recipients With COVID-19

Nirmatrelvir/ritonavir is a promising option for preventing severe COVID-19 in solid organ transplant recipients with SARS-CoV-2 infection. However, concerns have arisen regarding potential drug interactions with calcineurin inhibitors (CNI). This two-phase multicentre retrospective study, involving 113 patients on tacrolimus and 13 on cyclosporine A, aimed to assess the feasibility and outcomes of recommendations issued by The French societies of transplantation (SFT) and pharmacology (SFPT) for CNI management in this context. The study first evaluated adherence to recommendations, CNI exposure, and clinical outcomes. Notably, 96.5% of patients on tacrolimus adhered to the recommendations, maintaining stable tacrolimus trough concentrations (C0) during nirmatrelvir/ritonavir treatment. After reintroduction, most patients experienced increased C0, with 42.9% surpassing 15 ng/mL, including three patients exceeding 40 ng/mL. Similar trends were observed in cyclosporine A patients, with no COVID-19-related hospitalizations. Moreover, data from 22 patients were used to refine the reintroduction strategy. Modelling analyses suggested reintroducing tacrolimus at 50% of the initial dose on day 8, and then at 100% from day 9 as the optimal approach. In conclusion, the current strategy effectively maintains consistent tacrolimus exposure during nirmatrelvir/ritonavir treatment, and a stepwise reintroduction of tacrolimus may be better suited to the low CYP3A recovery.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Safety, Efficacy and Relapse of Nirmatrelvir-Ritonavir in Kidney Transplant Recipients Infected with SARS-CoV-2

International audienceINTRODUCTION: Nirmatrelvir-ritonavir (NR) has demonstrated its efficacy to decrease the risk of progression to severe COVID-19 in high-risk patients. However, evidence in infected kidney transplant recipients (KTRs) is lacking. Moreover, NR has significant and potentially harmful interactions with calcineurin inhibitors (CNIs). METHODS: In this single-center retrospective study, we included all KTRs treated with NR from April 28(th) to June 3(th), 2022. A standard management strategy of CNIs dose adaptation (discontinuation of tacrolimus 12 hours before the start of NR and administration of 20% the cyclosporine dose) and laboratory follow-up was applied. RESULTS: Fourteen patients were included. Compared to day-0 (day before NR initiation), day-7 plasma creatinine concentrations and SARS-CoV-2 viral loads were similar (p = 0.866) and decreased (p=0.002), respectively. CNIs trough concentrations at the end of the treatment were satisfactory, with nevertheless high individual variability. After a median follow-up time of 34 days, no death nor viral pneumonia were observed. However, 2 patients experienced early SARS-CoV-2 infection relapses (at day-10 and day-21) associated with an increase in SARS-CoV-2 viral loads. CONCLUSIONS: NR can be used in KTRs but requires a strict protocol of drug adaptation. We observed two cases of early relapse after NR treatment that need further investigations