| アブストラクト | BACKGROUND: A highly effective therapy involving elexacaftor, tezacaftor, and ivacaftor (ETI) for cystic fibrosis (CF) patients has recently raised safety concerns regarding potential psychiatric disorders. The manuscript reports cases of suicide attempts in patients receiving ETI and investigates putative causality using the WHO spontaneous reporting database. METHODS: First, four cases of suicide attempts/self-injury are described. Second, a disproportionality analysis was conducted using spontaneous reports collected in Vigibase through the standardised MedDRA Query (narrow version) "Suicide/Self-injury" and ETI exposure. Reporting Odds Ratio (ROR) was calculated for the main and subgroup (i/suicide attempt, ii/suicidal ideation) analyses. Sensitivity analyses were performed with variations in exposure, to ivacaftor/lumacaftor to assess the intrinsic psychiatric risk of CF patients, and paracetamol as a positive control for suicide attempt and a negative one for suicidal ideation. Exposure to reduced-dose ETI was studied to evaluate the dose-gradient effect. RESULTS: Four cases of suicide attempt/self-injury occurred 3 to 13 months after ETI initiation in CF patients and were reported to the Bordeaux Pharmacovigilance centre. Aside, in Vigibase, ETI is associated with an increased likelihood of reporting suicidal behaviour (ROR 2.5, 95 % CI[2.1; 2.8]). A signal of disproportionate reporting was found for the subgroup of suicide attempts (1.4, 95 % CI[1.2; 1.8]), unlike ivacaftor/lumacaftor, which was associated only with the risk of reporting suicidal ideation. Significant ROR values were also found for reduced-dose ETI for all psychiatric effects studied except suicide attempt. CONCLUSIONS: ETI exposure is related with increased reporting of suicidal behaviour. A potential dose-dependent effect merits further investigation. |
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| ジャーナル名 | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society |
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| 投稿日 | 2024/10/16 |
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| 投稿者 | Nidegger, Ines; Macey, Julie; Ferey, Marine; Singier, Allison; Tournier, Marie; Perino, Justine; Salvo, Francesco |
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| 組織名 | CHU de Bordeaux, Service de Pharmacologie Medicale, Centre Regional de;Pharmacovigilance de Bordeaux, F-33000 Bordeaux.;Service de Pneumologie, CHU Bordeaux, F-33000 Bordeaux, France.;Service de Pharmacie, Centre Hospitalier de Charles Perrens, F-33000 Bordeaux,;France.;Universite de Bordeaux, INSERM, Bordeaux Population Health, U1219, AHeaD Team,;F-33000 Bordeaux, France.;F-33000 Bordeaux, France; Charles Perrens Hospital, F-33000 Bordeaux, France.;Pharmacovigilance de Bordeaux, F-33000 Bordeaux; Universite de Bordeaux, INSERM,;Bordeaux Population Health, U1219, AHeaD Team, F-33000 Bordeaux, France.;Electronic address: francesco.salvo@u-bordeaux.fr. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/39406576/ |
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