Predicting therapy response to mycophenolic acid using UGT1A9 genotyping: towards personalized medicine in atopic dermatitis
Atopic dermatitis (AD) is a very common chronic inflammatory skin disease requiring long-term treatment. Mycophenolic acid (MPA) is used off-label in treatment of patients with severe AD failing Cyclosporin A (CsA) treatment, however clinical efficacy is observed in only half of the AD patients. In...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-04-01
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| Series: | Journal of Dermatological Treatment |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/09546634.2016.1227420 |
| _version_ | 1797684024046518272 |
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| author | J. L. Thijs B. A. M. Van Der Geest J. Van Der Schaft M. P. Van Den Broek W. O. Van Seggelen C. A. F. Bruijnzeel-Koomen D. J. Hijnen R. H. Van Schaik M. S. De Bruin-Weller |
| author_facet | J. L. Thijs B. A. M. Van Der Geest J. Van Der Schaft M. P. Van Den Broek W. O. Van Seggelen C. A. F. Bruijnzeel-Koomen D. J. Hijnen R. H. Van Schaik M. S. De Bruin-Weller |
| author_sort | J. L. Thijs |
| collection | DOAJ |
| description | Atopic dermatitis (AD) is a very common chronic inflammatory skin disease requiring long-term treatment. Mycophenolic acid (MPA) is used off-label in treatment of patients with severe AD failing Cyclosporin A (CsA) treatment, however clinical efficacy is observed in only half of the AD patients. In blood, MPA levels are known to have a large interindividual variability. Low MPA exposure and increased enzyme activity correlates with the presence of UGT1A9 polymorphisms. In this retrospective study, 65 adult AD patients treated with MPA were classified as responder or non-responder to MPA treatment. UGT1A9 polymorphisms were determined using PCR. A significantly higher number of UGT1A9 polymorphisms was found in the group that did not respond to MPA treatment. Of the patients that carried a UGT1A9 polymorphism, 85.7% were non-responsive to MPA treatment. This implies that non-responsiveness in AD patients is more likely to occur in carriers of a UGT1A9 polymorphism. In a binary logistic regression analysis the odds ratio (OR) was 8.65 (95% confidence interval: 0.93–80.17). Our results show that UGT1A9 polymorphisms can be used to identify patients with non-responsiveness to MPA. Patients with UGT1A9 polymorphisms might benefit from higher MPA dosage. |
| first_indexed | 2024-03-12T00:23:22Z |
| format | Article |
| id | doaj.art-b4d4d0258a6c49f2afd9a263e270abb4 |
| institution | Directory Open Access Journal |
| issn | 0954-6634 1471-1753 |
| language | English |
| last_indexed | 2024-03-12T00:23:22Z |
| publishDate | 2017-04-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Dermatological Treatment |
| spelling | doaj.art-b4d4d0258a6c49f2afd9a263e270abb42023-09-15T10:48:03ZengTaylor & Francis GroupJournal of Dermatological Treatment0954-66341471-17532017-04-0128324224510.1080/09546634.2016.12274201227420Predicting therapy response to mycophenolic acid using UGT1A9 genotyping: towards personalized medicine in atopic dermatitisJ. L. Thijs0B. A. M. Van Der Geest1J. Van Der Schaft2M. P. Van Den Broek3W. O. Van Seggelen4C. A. F. Bruijnzeel-Koomen5D. J. Hijnen6R. H. Van Schaik7M. S. De Bruin-Weller8Department of Dermatology and AllergologyDepartment of Dermatology and AllergologyDepartment of Dermatology and AllergologyDepartment of Clinical PharmacyDepartment of Dermatology and AllergologyDepartment of Dermatology and AllergologyDepartment of Dermatology and AllergologyUniversity Medical Center UtrechtDepartment of Dermatology and AllergologyAtopic dermatitis (AD) is a very common chronic inflammatory skin disease requiring long-term treatment. Mycophenolic acid (MPA) is used off-label in treatment of patients with severe AD failing Cyclosporin A (CsA) treatment, however clinical efficacy is observed in only half of the AD patients. In blood, MPA levels are known to have a large interindividual variability. Low MPA exposure and increased enzyme activity correlates with the presence of UGT1A9 polymorphisms. In this retrospective study, 65 adult AD patients treated with MPA were classified as responder or non-responder to MPA treatment. UGT1A9 polymorphisms were determined using PCR. A significantly higher number of UGT1A9 polymorphisms was found in the group that did not respond to MPA treatment. Of the patients that carried a UGT1A9 polymorphism, 85.7% were non-responsive to MPA treatment. This implies that non-responsiveness in AD patients is more likely to occur in carriers of a UGT1A9 polymorphism. In a binary logistic regression analysis the odds ratio (OR) was 8.65 (95% confidence interval: 0.93–80.17). Our results show that UGT1A9 polymorphisms can be used to identify patients with non-responsiveness to MPA. Patients with UGT1A9 polymorphisms might benefit from higher MPA dosage.http://dx.doi.org/10.1080/09546634.2016.1227420atopic dermatitismycophenolic acidugt1a9pharmacogenomics |
| spellingShingle | J. L. Thijs B. A. M. Van Der Geest J. Van Der Schaft M. P. Van Den Broek W. O. Van Seggelen C. A. F. Bruijnzeel-Koomen D. J. Hijnen R. H. Van Schaik M. S. De Bruin-Weller Predicting therapy response to mycophenolic acid using UGT1A9 genotyping: towards personalized medicine in atopic dermatitis Journal of Dermatological Treatment atopic dermatitis mycophenolic acid ugt1a9 pharmacogenomics |
| title | Predicting therapy response to mycophenolic acid using UGT1A9 genotyping: towards personalized medicine in atopic dermatitis |
| title_full | Predicting therapy response to mycophenolic acid using UGT1A9 genotyping: towards personalized medicine in atopic dermatitis |
| title_fullStr | Predicting therapy response to mycophenolic acid using UGT1A9 genotyping: towards personalized medicine in atopic dermatitis |
| title_full_unstemmed | Predicting therapy response to mycophenolic acid using UGT1A9 genotyping: towards personalized medicine in atopic dermatitis |
| title_short | Predicting therapy response to mycophenolic acid using UGT1A9 genotyping: towards personalized medicine in atopic dermatitis |
| title_sort | predicting therapy response to mycophenolic acid using ugt1a9 genotyping towards personalized medicine in atopic dermatitis |
| topic | atopic dermatitis mycophenolic acid ugt1a9 pharmacogenomics |
| url | http://dx.doi.org/10.1080/09546634.2016.1227420 |
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