{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T02:12:18Z","timestamp":1787969538971,"version":"build-2784847793"},"reference-count":12,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T00:00:00Z","timestamp":1621382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:p>Although several spontaneous case reports on the occurrence of thrombocytopenia in patients treated with human granulocyte colony\u2010stimulating factor (G\u2010CSF) preparations have been accumulated, its actual causality is still unclear. To investigate the association between G\u2010CSF preparations (filgrastim, nartograstim, lenograstim, and pegfilgrastim) available in Japan and thrombocytopenia in patients treated with antineoplastic agents, a nested case\u2010control study was conducted using the Medical Information Database NETwork (MID\u2010NET\u00ae) with the cohort of the Japanese population taking antineoplastic agents between 2009 and 2018. A case of thrombocytopenia was defined as a patient who had decreased platelet counts (&lt;\u00a050,000\/mm<jats:sup>3<\/jats:sup>). We identified a maximum of 10 controls for each case matched on the index date. Adjusted odds ratios (aORs) and their 95% confidence intervals (CIs) of thrombocytopenia for the use of G\u2010CSF preparations compared with nonuse were estimated using conditional logistic regression. From the cohort in which 33,124 patients were included, 733 cases and 5,592 controls were identified. Compared with the nonuse of G\u2010CSF preparations, the use of any G\u2010CSF preparations increased the risk of thrombocytopenia (aOR: 5.7, 95% CI: 4.3\u20107.5). More detailed analysis showed that a distinctive increased risk was observed when pegfilgrastim was prescribed at 2\u20137\u00a0days before the index date (aOR: 7.4 95% CI: 2.0\u201328.1). Associations of the other G\u2010CSF preparations with thrombocytopenia were unclear due to the inconsistent results among different analyses. A significantly increased risk of thrombocytopenia associated with pegfilgrastim was identified, leading to a revision of precautions in the package inserts of pegfilgrastim as a regulatory safety action.<\/jats:p>","DOI":"10.1002\/cpt.2263","type":"journal-article","created":{"date-parts":[[2021,4,18]],"date-time":"2021-04-18T18:18:01Z","timestamp":1618769881000},"page":"473-479","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Nested Case\u2010Control Study Utilizing MID\u2010NET\u00ae on Thrombocytopenia Associated With Pegfilgrastim in Patients Treated With Antineoplastic Agents"],"prefix":"10.1111","volume":"110","author":[{"given":"Kazuhiro","family":"Kajiyama","sequence":"first","affiliation":[{"name":"Office of Medical Informatics and Epidemiology, Pharmaceuticals and Medical Devices Agency Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieko","family":"Ishiguro","sequence":"additional","affiliation":[{"name":"Office of Medical Informatics and Epidemiology, Pharmaceuticals and Medical Devices Agency Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ando","sequence":"additional","affiliation":[{"name":"Office of Medical Informatics and Epidemiology, Pharmaceuticals and Medical Devices Agency Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kubota","sequence":"additional","affiliation":[{"name":"Office of Pharmacovigilance I, Pharmaceuticals and Medical Devices Agency Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsumi","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Office of Pharmacovigilance II, Pharmaceuticals and Medical Devices Agency Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Oniyama","sequence":"additional","affiliation":[{"name":"Office of Pharmacovigilance I, Pharmaceuticals and Medical Devices Agency Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toyotaka","family":"Iguchi","sequence":"additional","affiliation":[{"name":"Office of Pharmacovigilance II, Pharmaceuticals and Medical Devices Agency Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Uyama","sequence":"additional","affiliation":[{"name":"Office of Medical Informatics and Epidemiology, Pharmaceuticals and Medical Devices Agency Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,19]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-017-3854-x"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-017-3842-1"},{"key":"e_1_2_11_3_1","unstructured":"Pharmaceuticals and Medical Devices Agency.Package insert of Pegfilgrastim (Genetical Recombination)subcutaneous injection 3.6mg [in Japanese]<https:\/\/www.info.pmda.go.jp\/go\/pack\/3399410G1020_1_08\/?view=frame&style=XML<=ja>. Accessed December 1 2020."},{"key":"e_1_2_11_4_1","unstructured":"Pharmaceuticals and Medical Devices Agency.Information for Spontaneous Case Reports suspected as Adverse Drug Reaction In Japan [in Japanese]<https:\/\/www.pmda.go.jp\/safety\/info\u2010services\/drugs\/adr\u2010info\/suspected\u2010adr\/0005.html>. Accessed December 1 2020."},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.4879"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.4777"},{"key":"e_1_2_11_7_1","unstructured":"Pharmaceuticals and Medical Devices Agency.Information for studies approved by the expert committee of MID\u2010NET\u00ae [in Japanese]<https:\/\/www.pmda.go.jp\/safety\/mid\u2010net\/0010.html>. Accessed December 1 2020."},{"key":"e_1_2_11_8_1","unstructured":"Act on the Pharmaceuticals and Medical Devices Agency (Act No.192 of 2002). [in Japanese] <https:\/\/elaws.e\u2010gov.go.jp\/document?lawid=414AC0000000192>. Accessed December 1 2020."},{"key":"e_1_2_11_9_1","unstructured":"Pharmarceuticals and Medical Devies Angency.MIHARI Project [in Japanese]<https:\/\/www.pmda.go.jp\/safety\/surveillance\u2010analysis\/0045.html>. Accessed December 1 2020."},{"key":"e_1_2_11_10_1","unstructured":"World Health Organization.ICD\u201010 : international statistical classification of diseases and related health problems : tenth revision 2nd ed<https:\/\/apps.who.int\/iris\/handle\/10665\/42980> (2004). Accessed December 1 2020."},{"key":"e_1_2_11_11_1","unstructured":"National Cancer Institute.Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events (CTCAE) v4.0<https:\/\/ctep.cancer.gov\/protocolDevelopment\/electronic_applications\/ctc.htm>. Accessed December 1 2020."},{"key":"e_1_2_11_12_1","unstructured":"Ministry of Health Labour and Welfare.Revision of Precautions. Pegfilgrastim (genetical recombination) [in Japanese]<https:\/\/www.pmda.go.jp\/files\/000234688.pdf> (2020). Accessed December 1 2020."}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.2263","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.2263","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.2263","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T13:38:29Z","timestamp":1699364309000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.2263"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,19]]},"references-count":12,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1002\/cpt.2263"],"URL":"https:\/\/doi.org\/10.1002\/cpt.2263","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,19]]},"assertion":[{"value":"2020-12-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}