Nested Case‐Control Study Utilizing MID‐NET® on Thrombocytopenia Associated With Pegfilgrastim in Patients Treated With Antineoplastic Agents

Abstract

Although several spontaneous case reports on the occurrence of thrombocytopenia in patients treated with human granulocyte colony-stimulating factor (G-CSF) preparations have been accumulated, its actual causality is still unclear. To investigate the association between G-CSF preparations (filgrastim, nartograstim, lenograstim, and pegfilgrastim) available in Japan and thrombocytopenia in patients treated with antineoplastic agents, a nested case-control study was conducted using the Medical Information Database NETwork (MID-NET®) 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 (< 50,000/mm 3 ). 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-CSF 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-CSF preparations, the use of any G-CSF preparations increased the risk of thrombocytopenia (aOR: 5.7, 95% CI: 4.3-7.5). More detailed analysis showed that a distinctive increased risk was observed when pegfilgrastim was prescribed at 2-7 days before the index date (aOR: 7.4 95% CI: 2.0-28.1). Associations of the other G-CSF 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.

A phase II study of FOLFIRINOX with primary prophylactic pegfilgrastim for chemotherapy-naïve Japanese patients with metastatic pancreatic cancer

“…With respect to adverse events other than FN, the incidence of grade 3 or higher thrombocytopenia in our study was higher than that in the Japanese modified FOLFIRINOX study (22.7 vs. 2.9%). Kajiyama et al reported from a large national database, that pegfilgrastim increased the risk of thrombocytopenia in Japanese patients treated with antineoplastic agents [25]. Therefore, as not only the doses of FOLFIRINOX, but also the dose of pegfilgrastim could have had an influence on the incidence of severe thrombocytopenia, careful attention should be paid when adding pegfilgrastim administration to the modified FOLFIRINOX regimen for Japanese patients with PC.…”

Use of National Database of Health Insurance Claims and Specific Health Checkups for examining practical utilization and safety signal of a drug to support regulatory assessment on postmarketing drug safety in Japan

“…Therefore, we selected the NDB as a data source for these studies. MID-NET R is usually selected for a study in which laboratory test results are necessary for analysis (29)(30)(31)(32). As described above, an understanding of the characteristics of each database is important to select a data source fit to a study purpose.…”

Continuous co-prescription of rebamipide prevents upper gastrointestinal bleeding in NSAID use for orthopaedic conditions: A nested case-control study using the LIFE Study database

“…Using routinely collected medical claims data, this observational study using a nested case-control study design [ 27 – 29 ] was conducted following the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines [ 30 ], RECORD (Reporting of Studies Conducted Using Observational Routinely-Collected Health Data) Statement [ 31 ], and ethical standards of the Declaration of Helsinki.…”