| アブストラクト | RATIONALE: CFTR modulators (CFTRms) have transformed cystic fibrosis care, yet concern exists regarding their mental health safety profile. OBJECTIVE: To provide further information, we conducted an analysis of CFTRm-related mental health disorders using two spontaneous pharmacovigilance reporting databases in real-world settings. METHODS: We analyzed reports from the French Pharmacovigilance Database (FPD) and VigiBase, the WHO global individual case safety reports database. Reports recorded between 2012 and 2024 involving any CFTRm and psychiatric disorders were included. In VigiBase, we conducted a case-non case, disproportionality analysis using the Reporting Odds Ratio (ROR), overall and stratified by age group (pediatrics vs. adults) and by CFTRm type. This study was conducted in accordance with the STROBE and the READUS-PV guidelines. RESULTS: In the FPD, 116 cases were analyzed. ELX/TEZ/IVA was suspected in 98% of cases and no single case was reported with ivacaftor alone. Sleep (61%), mood (37%), and anxiety disorders (27%) were the most frequently reported, with suicidal behaviors being infrequent, including 6 suicide attempts and no completed suicide. In VigiBase (n = 3,407), sleep disorders predominated in children, whereas mood and suicidality disorders were most frequent in adolescents. The median time to onset was 60 days (Q1-Q3: 12-150 days). Mental health disorders were disproportionately reported with CFTRms, particularly ELX/TEZ/IVA, while they were not with other combination therapies, compared to other drugs in the database. Disproportionality signals were slightly stronger in pediatrics than in adults. CONCLUSIONS: CFTRms, especially ELX/TEZ/IVA, are associated with increased reporting of mental health disorders, predominantly sleep and mood disorders. Pediatrics appear to be particularly affected. Prospective observational studies are warranted to confirm these findings and elucidate underlying pathophysiological mechanisms. REGISTRATION: OSF: mfyx3. |
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| 投稿者 | Merino, Diane A; Cohen, Samuel D; Ben Othman, Nouha; Osmont, Marie-Noelle; Pietri, Tessa; Bergeron, Sandrine; Gautier, Sophie; Rocher, Fanny; Drici, Milou-Daniel; Burgel, Pierre-Regis; Sermet-Gaudelus, Isabelle; Gerard, Alexandre O; Chouchana, Laurent |
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| 組織名 | University Department of Child and Adolescent Psychiatry, Children's Hospitals of;Nice, CHU-Lenval, Nice, France.;Department of Clinical Pharmacology and Pharmacovigilance Center of Nice,;University Hospital of Nice, Universite Cote d'Azur, Nice, France.;Regional Center of Pharmacovigilance, Department of perinatal, pediatric and;adult pharmacology, Hopital Cochin, Hopital Necker, Assistance Publique -;Hopitaux de Paris. Paris, France.;Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Department;of Clinical Pharmacology, Rennes University Hospital, 35033, Rennes, France.;Service de pharmacologie Clinique & Pharmacosurveillance, Centre regional de;pharmacovigilance Marseille Provence Corse, AMU INSERM 1106 Institut de;Neurosciences des Systemes, Assistance Publique - Hopitaux de Marseille,;Marseille, France.;Regional Pharmacovigilance Centre Lille, Clinical Pharmacology Department, U 1171;University Hospital of Lille, University of Lille, F-59000 Lille, France.;Hopital Cochin and Cystic Fibrosis National Reference Center, Service de;Pneumologie, Assistance Publique-Hopitaux de Paris, Paris.;Centre de Reference Maladies Rares Mucoviscidose et Maladies Apparentees, Hopital;Necker Enfants malades, Assistance Publique Hopitaux de Paris, Groupe Hospitalier;Paris Centre, Institut Necker Enfants Malades, INSERM U1151, Paris 75015, France.;ERN Lung, Frankfurt, Germany. |
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