Optimization of Rituximab Therapy in Adult Patients With PLA2R1-Associated Membranous Nephropathy With Artificial Intelligence
Rituximab is a first-line treatment for membranous nephropathy. Nephrotic syndrome limits rituximab exposure due to urinary drug loss. Rituximab underdosing (serum level
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| Veröffentlicht in: | Kidney international reports 2024-01, Vol.9 (1), p.134-144 |
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| creator | Destere, Alexandre Teisseyre, Maxime Merino, Diane Cremoni, Marion Gérard, Alexandre O Crepin, Thomas Jourde-Chiche, Noémie Graça, Daisy Zorzi, Kévin Fernandez, Céline Brglez, Vesna Benzaken, Sylvia Esnault, Vincent L M Benito, Sylvain Drici, Milou-Daniel Seitz-Polski, Barbara |
| description | Rituximab is a first-line treatment for membranous nephropathy. Nephrotic syndrome limits rituximab exposure due to urinary drug loss. Rituximab underdosing (serum level |
| doi_str_mv | 10.1016/j.ekir.2023.10.023 |
| format | Article |
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Rituximab concentrations were measured at month-3 in 92 sera from adult patients with primary membranous nephropathy, split into a training (75%) and a testing set (25%). A forward-backward machine-learning procedure determined the best combination of variables to predict rituximab underdosing in the training data set, which was tested in the test set. The performances were evaluated for accuracy, sensitivity, and specificity in 10-fold cross-validation training and test sets.
The best variables combination to predict rituximab underdosing included age, gender, body surface area (BSA), anti-phospholipase A2 receptor type 1 (anti-PLA2R1) antibody titer on day-0, serum albumin on day-0 and day-15, and serum creatinine on day-0 and day-15. The accuracy, sensitivity, and specificity were respectively 79.4%, 78.7%, and 81.0% (training data set), and 79.2%, 84.6% and 72.7% (testing data set). In both sets, the algorithm performed significantly better than chance (
< 0.05). Patients with an initial high probability of underdosing experienced a longer time to remission with higher rituximab cumulative doses required to achieved remission.
This algorithm could allow for early intensification of rituximab regimen in patients at high estimated risk of underdosing to increase the likelihood of remission.</description><identifier>ISSN: 2468-0249</identifier><identifier>EISSN: 2468-0249</identifier><identifier>DOI: 10.1016/j.ekir.2023.10.023</identifier><identifier>PMID: 38312797</identifier><language>eng</language><publisher>United States: Elsevier</publisher><subject>Artificial Intelligence ; Clinical Research ; Computer Science ; Human health and pathology ; Immunology ; Immunotherapy ; Life Sciences ; Urology and Nephrology</subject><ispartof>Kidney international reports, 2024-01, Vol.9 (1), p.134-144</ispartof><rights>2023 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2023 Published by Elsevier, Inc., on behalf of the International Society of Nephrology. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c437t-d648abac9710b3e8a1c7702e988bf60062a64f810d6b0015e16bd0f3ac6006e73</citedby><cites>FETCH-LOGICAL-c437t-d648abac9710b3e8a1c7702e988bf60062a64f810d6b0015e16bd0f3ac6006e73</cites><orcidid>0000-0001-9315-1577</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10831377/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10831377/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38312797$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04321277$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Destere, Alexandre</creatorcontrib><creatorcontrib>Teisseyre, Maxime</creatorcontrib><creatorcontrib>Merino, Diane</creatorcontrib><creatorcontrib>Cremoni, Marion</creatorcontrib><creatorcontrib>Gérard, Alexandre O</creatorcontrib><creatorcontrib>Crepin, Thomas</creatorcontrib><creatorcontrib>Jourde-Chiche, Noémie</creatorcontrib><creatorcontrib>Graça, Daisy</creatorcontrib><creatorcontrib>Zorzi, Kévin</creatorcontrib><creatorcontrib>Fernandez, Céline</creatorcontrib><creatorcontrib>Brglez, Vesna</creatorcontrib><creatorcontrib>Benzaken, Sylvia</creatorcontrib><creatorcontrib>Esnault, Vincent L M</creatorcontrib><creatorcontrib>Benito, Sylvain</creatorcontrib><creatorcontrib>Drici, Milou-Daniel</creatorcontrib><creatorcontrib>Seitz-Polski, Barbara</creatorcontrib><title>Optimization of Rituximab Therapy in Adult Patients With PLA2R1-Associated Membranous Nephropathy With Artificial Intelligence</title><title>Kidney international reports</title><addtitle>Kidney Int Rep</addtitle><description>Rituximab is a first-line treatment for membranous nephropathy. Nephrotic syndrome limits rituximab exposure due to urinary drug loss. Rituximab underdosing (serum level <2 μg/ml at month-3) is a risk factor for treatment failure. We developed a machine learning algorithm to predict the risk of underdosing based on patients' characteristics at rituximab infusion. We investigated the relationship between the predicted risk of underdosing and the cumulative dose of rituximab required to achieve remission.
Rituximab concentrations were measured at month-3 in 92 sera from adult patients with primary membranous nephropathy, split into a training (75%) and a testing set (25%). A forward-backward machine-learning procedure determined the best combination of variables to predict rituximab underdosing in the training data set, which was tested in the test set. The performances were evaluated for accuracy, sensitivity, and specificity in 10-fold cross-validation training and test sets.
The best variables combination to predict rituximab underdosing included age, gender, body surface area (BSA), anti-phospholipase A2 receptor type 1 (anti-PLA2R1) antibody titer on day-0, serum albumin on day-0 and day-15, and serum creatinine on day-0 and day-15. The accuracy, sensitivity, and specificity were respectively 79.4%, 78.7%, and 81.0% (training data set), and 79.2%, 84.6% and 72.7% (testing data set). In both sets, the algorithm performed significantly better than chance (
< 0.05). Patients with an initial high probability of underdosing experienced a longer time to remission with higher rituximab cumulative doses required to achieved remission.
This algorithm could allow for early intensification of rituximab regimen in patients at high estimated risk of underdosing to increase the likelihood of remission.</description><subject>Artificial Intelligence</subject><subject>Clinical Research</subject><subject>Computer Science</subject><subject>Human health and pathology</subject><subject>Immunology</subject><subject>Immunotherapy</subject><subject>Life Sciences</subject><subject>Urology and Nephrology</subject><issn>2468-0249</issn><issn>2468-0249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNpdUU1v1DAUtBCIVqV_gAPyEQ5Z_JG1kxOKqkIrLW1VFXG0HOel8ZLEwXYqlgO_HUfbVm1Pz5o3M9a8Qeg9JStKqPi8XcEv61eMMJ6AVRqv0CHLRZERlpevn7wP0HEIW0IIlWJdkuItOuAFp0yW8hD9u5yiHexfHa0bsWvxtY3zHzvoGt904PW0w3bEVTP3EV8lEowx4J82dvhqU7FrmlUhOGN1hAZ_h6H2enRzwBcwdd5NOna7Pbvy0bY2EXt8Pkboe3sLo4F36E2r-wDH9_MI_fh6enNylm0uv52fVJvM5FzGrBF5oWttSklJzaHQ1EhJGJRFUbeCEMG0yNuCkkbUKecaqKgb0nJtliVIfoS-7H2nuR6gMSmG172afErqd8ppq55vRtupW3enKEmn4nJx-LR36F7ozqqNWjCSc5aOKu9o4n68_8273zOEqAYbTAqtR0jXUaxkLF_zXLJEZXuq8S4ED-2jNyVqKVpt1VK0WopesDSS6MPTNI-Sh1r5f4HXppY</recordid><startdate>20240101</startdate><enddate>20240101</enddate><creator>Destere, Alexandre</creator><creator>Teisseyre, Maxime</creator><creator>Merino, Diane</creator><creator>Cremoni, Marion</creator><creator>Gérard, Alexandre O</creator><creator>Crepin, Thomas</creator><creator>Jourde-Chiche, Noémie</creator><creator>Graça, Daisy</creator><creator>Zorzi, Kévin</creator><creator>Fernandez, Céline</creator><creator>Brglez, Vesna</creator><creator>Benzaken, Sylvia</creator><creator>Esnault, Vincent L M</creator><creator>Benito, Sylvain</creator><creator>Drici, Milou-Daniel</creator><creator>Seitz-Polski, Barbara</creator><general>Elsevier</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9315-1577</orcidid></search><sort><creationdate>20240101</creationdate><title>Optimization of Rituximab Therapy in Adult Patients With PLA2R1-Associated Membranous Nephropathy With Artificial Intelligence</title><author>Destere, Alexandre ; 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Nephrotic syndrome limits rituximab exposure due to urinary drug loss. Rituximab underdosing (serum level <2 μg/ml at month-3) is a risk factor for treatment failure. We developed a machine learning algorithm to predict the risk of underdosing based on patients' characteristics at rituximab infusion. We investigated the relationship between the predicted risk of underdosing and the cumulative dose of rituximab required to achieve remission.
Rituximab concentrations were measured at month-3 in 92 sera from adult patients with primary membranous nephropathy, split into a training (75%) and a testing set (25%). A forward-backward machine-learning procedure determined the best combination of variables to predict rituximab underdosing in the training data set, which was tested in the test set. The performances were evaluated for accuracy, sensitivity, and specificity in 10-fold cross-validation training and test sets.
The best variables combination to predict rituximab underdosing included age, gender, body surface area (BSA), anti-phospholipase A2 receptor type 1 (anti-PLA2R1) antibody titer on day-0, serum albumin on day-0 and day-15, and serum creatinine on day-0 and day-15. The accuracy, sensitivity, and specificity were respectively 79.4%, 78.7%, and 81.0% (training data set), and 79.2%, 84.6% and 72.7% (testing data set). In both sets, the algorithm performed significantly better than chance (
< 0.05). Patients with an initial high probability of underdosing experienced a longer time to remission with higher rituximab cumulative doses required to achieved remission.
This algorithm could allow for early intensification of rituximab regimen in patients at high estimated risk of underdosing to increase the likelihood of remission.</abstract><cop>United States</cop><pub>Elsevier</pub><pmid>38312797</pmid><doi>10.1016/j.ekir.2023.10.023</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-9315-1577</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Artificial Intelligence Clinical Research Computer Science Human health and pathology Immunology Immunotherapy Life Sciences Urology and Nephrology |
| title | Optimization of Rituximab Therapy in Adult Patients With PLA2R1-Associated Membranous Nephropathy With Artificial Intelligence |
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