Analysis of adverse events with ruxolitinib using real-world datasets and drug-interaction networks
Objectives: Ruxolitinib is used to treat myelofibrosis, polycythemia vera, and steroid-refractory graft-versus-host disease following allogeneic stem cell transplantation. This study aimed to determine the association between ruxolitinib and adverse events by evaluating case reports published betwee...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2025-06-01
|
| Series: | SAGE Open Medicine |
| Online Access: | https://doi.org/10.1177/20503121251348420 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850167115546361856 |
|---|---|
| author | Hideyuki Tanaka Mika Maezawa Mizuki Tanaka Ryogo Umetsu Sakiko Hirofuji Koumi Miyasaka Satoshi Nakao Yuka Nokura Moe Yamashita Nanaka Ichihara Kana Sugishita Tomofumi Yamazaki Kohei Shiota Hirofumi Tamaki Kazuhiro Iguchi Mitsuhiro Nakamura |
| author_facet | Hideyuki Tanaka Mika Maezawa Mizuki Tanaka Ryogo Umetsu Sakiko Hirofuji Koumi Miyasaka Satoshi Nakao Yuka Nokura Moe Yamashita Nanaka Ichihara Kana Sugishita Tomofumi Yamazaki Kohei Shiota Hirofumi Tamaki Kazuhiro Iguchi Mitsuhiro Nakamura |
| author_sort | Hideyuki Tanaka |
| collection | DOAJ |
| description | Objectives: Ruxolitinib is used to treat myelofibrosis, polycythemia vera, and steroid-refractory graft-versus-host disease following allogeneic stem cell transplantation. This study aimed to determine the association between ruxolitinib and adverse events by evaluating case reports published between January 2014 and March 2024 in the Japanese Adverse Drug Event Report database. Methods: The signals for the ruxolitinib–adverse event association were identified using propensity score-adjusted reporting odds ratio analysis. Data obtained from the drug–gene interaction, drug signature, search tool for chemical interactions, and interaction reference index databases were used to construct a drug–gene interaction network. Functional and pathway enrichment analyses were performed using the Disease Ontology Semantic and Enrichment and ReactomePA R packages. Results: The propensity score-adjusted reporting odds ratio for ruxolitinib-associated adverse events was as follows: anemia, 18.49 (95% confidence interval (CI): 16.15–21.16); myelosuppression, 4.70 (95% CI: 3.54–6.24); pancytopenia, 1.97 (95% CI: 1.23–3.16); cardiac failure, 2.29 (95% CI: 1.60–3.28); hepatic function abnormal, 1.60 (95% CI: 1.15–2.23); herpes zoster, 6.40 (95% CI: 4.35–9.41); pneumonia, 2.96 (95% CI: 2.35–3.73); renal impairment, 1.34 (95% CI: 0.94–1.90); sepsis, 5.14 (95% CI: 3.75–7.05); interstitial lung disease, 0.33 (95% CI: 0.21–0.52); deep vein thrombosis, 0.32 (95% CI: 0.07–1.44); hemorrhage, 1.99 (95% CI: 1.05–3.75). We also assessed 3015 human genes that directly or indirectly interact with ruxolitinib. The molecular complex detection plug-in of Cytoscape was used to detect 24 clusters. Several genes were enriched in the biological processes of “anemia” and “bacterial infections,” identified as significant ruxolitinib-related disease terms. Conclusions: This retrospective analysis using the Japanese Adverse Drug Event Report database indicated potential associations between ruxolitinib and adverse events, including anemia and bacterial infections. Future research should explore the underlying pharmacological mechanisms using functional enrichment analysis of ruxolitinib-associated genes related to blood toxicity and bacterial infections. |
| format | Article |
| id | doaj-art-bc8d12ae61134abca26862b66166e30b |
| institution | OA Journals |
| issn | 2050-3121 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | SAGE Open Medicine |
| spelling | doaj-art-bc8d12ae61134abca26862b66166e30b2025-08-20T02:21:16ZengSAGE PublishingSAGE Open Medicine2050-31212025-06-011310.1177/20503121251348420Analysis of adverse events with ruxolitinib using real-world datasets and drug-interaction networksHideyuki Tanaka0Mika Maezawa1Mizuki Tanaka2Ryogo Umetsu3Sakiko Hirofuji4Koumi Miyasaka5Satoshi Nakao6Yuka Nokura7Moe Yamashita8Nanaka Ichihara9Kana Sugishita10Tomofumi Yamazaki11Kohei Shiota12Hirofumi Tamaki13Kazuhiro Iguchi14Mitsuhiro Nakamura15Chubuyakuhin Co., Ltd., Tajimi-shi, Gifu, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, JapanDepartment of Pharmacy, Kyushu University Hospital, Higashi-ku, Fukuoka, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, JapanLaboratory of Community Pharmacy, Gifu Pharmaceutical University, Gifu-shi, JapanLaboratory of Community Pharmacy, Gifu Pharmaceutical University, Gifu-shi, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, JapanObjectives: Ruxolitinib is used to treat myelofibrosis, polycythemia vera, and steroid-refractory graft-versus-host disease following allogeneic stem cell transplantation. This study aimed to determine the association between ruxolitinib and adverse events by evaluating case reports published between January 2014 and March 2024 in the Japanese Adverse Drug Event Report database. Methods: The signals for the ruxolitinib–adverse event association were identified using propensity score-adjusted reporting odds ratio analysis. Data obtained from the drug–gene interaction, drug signature, search tool for chemical interactions, and interaction reference index databases were used to construct a drug–gene interaction network. Functional and pathway enrichment analyses were performed using the Disease Ontology Semantic and Enrichment and ReactomePA R packages. Results: The propensity score-adjusted reporting odds ratio for ruxolitinib-associated adverse events was as follows: anemia, 18.49 (95% confidence interval (CI): 16.15–21.16); myelosuppression, 4.70 (95% CI: 3.54–6.24); pancytopenia, 1.97 (95% CI: 1.23–3.16); cardiac failure, 2.29 (95% CI: 1.60–3.28); hepatic function abnormal, 1.60 (95% CI: 1.15–2.23); herpes zoster, 6.40 (95% CI: 4.35–9.41); pneumonia, 2.96 (95% CI: 2.35–3.73); renal impairment, 1.34 (95% CI: 0.94–1.90); sepsis, 5.14 (95% CI: 3.75–7.05); interstitial lung disease, 0.33 (95% CI: 0.21–0.52); deep vein thrombosis, 0.32 (95% CI: 0.07–1.44); hemorrhage, 1.99 (95% CI: 1.05–3.75). We also assessed 3015 human genes that directly or indirectly interact with ruxolitinib. The molecular complex detection plug-in of Cytoscape was used to detect 24 clusters. Several genes were enriched in the biological processes of “anemia” and “bacterial infections,” identified as significant ruxolitinib-related disease terms. Conclusions: This retrospective analysis using the Japanese Adverse Drug Event Report database indicated potential associations between ruxolitinib and adverse events, including anemia and bacterial infections. Future research should explore the underlying pharmacological mechanisms using functional enrichment analysis of ruxolitinib-associated genes related to blood toxicity and bacterial infections.https://doi.org/10.1177/20503121251348420 |
| spellingShingle | Hideyuki Tanaka Mika Maezawa Mizuki Tanaka Ryogo Umetsu Sakiko Hirofuji Koumi Miyasaka Satoshi Nakao Yuka Nokura Moe Yamashita Nanaka Ichihara Kana Sugishita Tomofumi Yamazaki Kohei Shiota Hirofumi Tamaki Kazuhiro Iguchi Mitsuhiro Nakamura Analysis of adverse events with ruxolitinib using real-world datasets and drug-interaction networks SAGE Open Medicine |
| title | Analysis of adverse events with ruxolitinib using real-world datasets and drug-interaction networks |
| title_full | Analysis of adverse events with ruxolitinib using real-world datasets and drug-interaction networks |
| title_fullStr | Analysis of adverse events with ruxolitinib using real-world datasets and drug-interaction networks |
| title_full_unstemmed | Analysis of adverse events with ruxolitinib using real-world datasets and drug-interaction networks |
| title_short | Analysis of adverse events with ruxolitinib using real-world datasets and drug-interaction networks |
| title_sort | analysis of adverse events with ruxolitinib using real world datasets and drug interaction networks |
| url | https://doi.org/10.1177/20503121251348420 |
| work_keys_str_mv | AT hideyukitanaka analysisofadverseeventswithruxolitinibusingrealworlddatasetsanddruginteractionnetworks AT mikamaezawa analysisofadverseeventswithruxolitinibusingrealworlddatasetsanddruginteractionnetworks AT mizukitanaka analysisofadverseeventswithruxolitinibusingrealworlddatasetsanddruginteractionnetworks AT ryogoumetsu analysisofadverseeventswithruxolitinibusingrealworlddatasetsanddruginteractionnetworks AT sakikohirofuji analysisofadverseeventswithruxolitinibusingrealworlddatasetsanddruginteractionnetworks AT koumimiyasaka analysisofadverseeventswithruxolitinibusingrealworlddatasetsanddruginteractionnetworks AT satoshinakao analysisofadverseeventswithruxolitinibusingrealworlddatasetsanddruginteractionnetworks AT yukanokura analysisofadverseeventswithruxolitinibusingrealworlddatasetsanddruginteractionnetworks AT moeyamashita analysisofadverseeventswithruxolitinibusingrealworlddatasetsanddruginteractionnetworks AT nanakaichihara analysisofadverseeventswithruxolitinibusingrealworlddatasetsanddruginteractionnetworks AT kanasugishita analysisofadverseeventswithruxolitinibusingrealworlddatasetsanddruginteractionnetworks AT tomofumiyamazaki analysisofadverseeventswithruxolitinibusingrealworlddatasetsanddruginteractionnetworks AT koheishiota analysisofadverseeventswithruxolitinibusingrealworlddatasetsanddruginteractionnetworks AT hirofumitamaki analysisofadverseeventswithruxolitinibusingrealworlddatasetsanddruginteractionnetworks AT kazuhiroiguchi analysisofadverseeventswithruxolitinibusingrealworlddatasetsanddruginteractionnetworks AT mitsuhironakamura analysisofadverseeventswithruxolitinibusingrealworlddatasetsanddruginteractionnetworks |