Leflunomide for BKvirus: Report of Seven Kidney-Transplanted Children
Background: Leflunomide is an immunosuppressive agent commercialized for treatment of rheumatoid arthritis. Because of its immunosuppressive and possible antiviral properties, leflunomide has been evaluated in some case series of BKVAN with favorable results, mostly in adult patients. Leflunomide ta...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Shiraz University of Medical Sciences
2018-10-01
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| Series: | International Journal of Organ Transplantation Medicine |
| Subjects: | |
| Online Access: | http://www.ijotm.com/ojs/index.php/IJOTM/article/view/515 |
| _version_ | 1818578716671868928 |
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| author | M Launay V Baudouin R Guillemain A Maisin H Flodrops E Douez S Mavoungou V Jullien E Billaud |
| author_facet | M Launay V Baudouin R Guillemain A Maisin H Flodrops E Douez S Mavoungou V Jullien E Billaud |
| author_sort | M Launay |
| collection | DOAJ |
| description | Background: Leflunomide is an immunosuppressive agent commercialized for treatment of rheumatoid arthritis. Because of its immunosuppressive and possible antiviral properties, leflunomide has been evaluated in some case series of BKVAN with favorable results, mostly in adult patients. Leflunomide targeted levels are usually between 50 and 100 mg/L in kidney transplant adult patients. Data in pediatric population are scarce.
Objective: To assess the effect of leflunomide on BKvirus in kidney-transplanted children.
Methods: Therapeutic drug monitoring of leflunomide is routinely performed by measuring its active metabolite, teriflunomide, using a simple HPLC-UV method. Pediatric kidney transplant patients with at least one teriflunomide sample between 2010 and 2017 were retrospectively included in this study. Viremia control was defined as undetectable BK viremia or a decrease of more than 1 log in the viral load from the baseline after two months of treatment. Adverse events were recorded.
Results: A total of 7 patients from 3 centers was included. 6 were only kidney transplant recipients; 1 was a lung-kidney transplant recipient with cystic fibrosis. All patients reported high load BK viremia but none developed BKVAN. For 67% of the patients, complete BK viral clearance was observed during leflunomide treatment with drastic immunosuppressive therapy reduction. Mycophenolate was indeed discontinued in almost all patients. Of note, leflunomide concentrations were significantly higher when viremia was controlled. Only 33% of the observed concentrations were >40 mg/L. The patient with cystic fibrosis had lower concentrations with higher drug doses. No hepatotoxicity was observed in this study and no patient experienced graft rejection. Leflunomide was suspected to cause hemolytic anemia and one patient experienced biological pancreatitis.
Conclusion: This study evidenced the wide interindividual variability of the exposure and supported the routine practice of leflunomide with a suggested target level of 30–40 mg/L in pediatric kidney transplanted patient. However, because of the very limited number of patients in our series, further investigations are needed to validate this suggestion. |
| first_indexed | 2024-12-16T06:50:14Z |
| format | Article |
| id | doaj.art-2c4cedc6edeb4dfb99d58c23ce65044c |
| institution | Directory Open Access Journal |
| issn | 2008-6482 2008-6490 |
| language | English |
| last_indexed | 2024-12-16T06:50:14Z |
| publishDate | 2018-10-01 |
| publisher | Shiraz University of Medical Sciences |
| record_format | Article |
| series | International Journal of Organ Transplantation Medicine |
| spelling | doaj.art-2c4cedc6edeb4dfb99d58c23ce65044c2022-12-21T22:40:24ZengShiraz University of Medical SciencesInternational Journal of Organ Transplantation Medicine2008-64822008-64902018-10-0194291Leflunomide for BKvirus: Report of Seven Kidney-Transplanted ChildrenM Launay0V Baudouin1R Guillemain2A Maisin3H Flodrops4E Douez5S Mavoungou6V Jullien7E Billaud8Laboratory of Pharmacology and Toxicology, European Hospital Georges Pompidou- APHPLaboratory of Pharmacology and Toxicology, European Hospital Georges Pompidou- APHPThoracic transplantation, European Hospital Georges Pompidou - APHPLaboratory of Pharmacology and Toxicology, European Hospital Georges Pompidou- APHPPediatry Department, Hospital of La ReunionLaboratory of Pharmacology and Toxicology, European Hospital Georges Pompidou - APHPLaboratory of Pharmacology and Toxicology, European Hospital Georges Pompidou - APHPLaboratory of Pharmacology and Toxicology, European Hospital Georges Pompidou - APHPLaboratory of Pharmacology and Toxicology, European Hospital Georges Pompidou - APHPBackground: Leflunomide is an immunosuppressive agent commercialized for treatment of rheumatoid arthritis. Because of its immunosuppressive and possible antiviral properties, leflunomide has been evaluated in some case series of BKVAN with favorable results, mostly in adult patients. Leflunomide targeted levels are usually between 50 and 100 mg/L in kidney transplant adult patients. Data in pediatric population are scarce. Objective: To assess the effect of leflunomide on BKvirus in kidney-transplanted children. Methods: Therapeutic drug monitoring of leflunomide is routinely performed by measuring its active metabolite, teriflunomide, using a simple HPLC-UV method. Pediatric kidney transplant patients with at least one teriflunomide sample between 2010 and 2017 were retrospectively included in this study. Viremia control was defined as undetectable BK viremia or a decrease of more than 1 log in the viral load from the baseline after two months of treatment. Adverse events were recorded. Results: A total of 7 patients from 3 centers was included. 6 were only kidney transplant recipients; 1 was a lung-kidney transplant recipient with cystic fibrosis. All patients reported high load BK viremia but none developed BKVAN. For 67% of the patients, complete BK viral clearance was observed during leflunomide treatment with drastic immunosuppressive therapy reduction. Mycophenolate was indeed discontinued in almost all patients. Of note, leflunomide concentrations were significantly higher when viremia was controlled. Only 33% of the observed concentrations were >40 mg/L. The patient with cystic fibrosis had lower concentrations with higher drug doses. No hepatotoxicity was observed in this study and no patient experienced graft rejection. Leflunomide was suspected to cause hemolytic anemia and one patient experienced biological pancreatitis. Conclusion: This study evidenced the wide interindividual variability of the exposure and supported the routine practice of leflunomide with a suggested target level of 30–40 mg/L in pediatric kidney transplanted patient. However, because of the very limited number of patients in our series, further investigations are needed to validate this suggestion.http://www.ijotm.com/ojs/index.php/IJOTM/article/view/515LeflunomideKidney transplantationPediatricsBK virusCystic fibrosisMycophenolate |
| spellingShingle | M Launay V Baudouin R Guillemain A Maisin H Flodrops E Douez S Mavoungou V Jullien E Billaud Leflunomide for BKvirus: Report of Seven Kidney-Transplanted Children International Journal of Organ Transplantation Medicine Leflunomide Kidney transplantation Pediatrics BK virus Cystic fibrosis Mycophenolate |
| title | Leflunomide for BKvirus: Report of Seven Kidney-Transplanted Children |
| title_full | Leflunomide for BKvirus: Report of Seven Kidney-Transplanted Children |
| title_fullStr | Leflunomide for BKvirus: Report of Seven Kidney-Transplanted Children |
| title_full_unstemmed | Leflunomide for BKvirus: Report of Seven Kidney-Transplanted Children |
| title_short | Leflunomide for BKvirus: Report of Seven Kidney-Transplanted Children |
| title_sort | leflunomide for bkvirus report of seven kidney transplanted children |
| topic | Leflunomide Kidney transplantation Pediatrics BK virus Cystic fibrosis Mycophenolate |
| url | http://www.ijotm.com/ojs/index.php/IJOTM/article/view/515 |
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