Pierre‐Marie Morice

Background Arterial hypertension has been recently reported from randomized controlled trials (RCTs) assessing poly (ADP‐ribose) polymerase inhibitor (PARPi). Objective In a context of increasing use of PARPi, it is crucial to properly assess risk and incidence of this adverse event for clinical practice. Methods We performed a systematic review and meta‐analysis in MEDLINE, Cochrane CENTRAL and ClinicalTrials.gov up to January 4, 2023 with an ongoing surveillance up to June 7, 2023. RCTs comparing PARPi to placebo in adult patients with solid tumors were included if hypertension was reported. The primary outcome was the summary risk ratio (RR, with 95% CIs) of any hypertension of PARPi class in placebo RCTs. Secondary outcomes were the summary risk and incidence of hypertension of each individual PARPi. To provide clinical features of PARPi‐associated hypertension, we independently queried the WHO's pharmacovigilance database, up to September 1, 2022. Results In total, 41 placebo RCTs ( n = 15 264 adult patients) were included. PARPi class was not associated with an increased risk of hypertension compared with placebo. In individual analyses, the risk of hypertension was lower with olaparib than placebo (RR 0.77 [95% CI: 0.68–0.86], P < 0.01; I 2 = 19%, χ 2 P = 0.26). Niraparib monotherapy increased the risk of any (RR 2.84 [95% CI: 1.76–4.57], P < 0.01; I 2 = 66%, χ 2 P = 0.01) hypertension with a summary incidence of 19.87% (95% CI: 15.23–25.50). In real‐life setting, niraparib‐associated hypertension occurs within 20 days and was serious in 66%. Co‐prescription of at least one antihypertensive or therapy‐induced hypertension was reported in 20.5% or 14.4% of cases, respectively. Conclusions In a context of extensive assessment of niraparib in combination, these data reinforce the need of a close monitoring of this adverse event to preserve its clinical benefit on patients' survival.

Aims Due to their central mechanism of action, antiseizure medications (ASMs) could lead to adverse effects likely to impair driving skills. Their extended use to neuropsychiatric disorders makes it a class of drugs to monitor for their road traffic accidental (RTA) potential. We aimed to assess the reporting association between ASMs and RTAs using the World Health Organization pharmacovigilance database (VigiBase). Methods We performed a disproportionality analysis to compute adjusted reporting odds ratios to evaluate the strength of reporting association between ASMs and RTAs. A univariate analysis using the reporting odds‐ratio was used to assess drug–drug interactions between ASMs and RTAs. Results There were 1 341 509 reports associated with at least 1 ASM in VigiBase of whom 2.91‰ were RTAs reports. Eight ASMs were associated with higher reporting of RTAs compared to others (ranging from 1.35 [95% confidence interval 1.11–1.64] for lamotrigine to 4.36 [95% confidence interval 3.56–5.32] for cannabis). Eight significant drug–drug interactions were found between ASMs and the onset of RTA, mainly involving CYP450 induction. Conclusion A significant safety signal between RTAs and some ASMs was identified. Association of several ASMs might further increase the occurrence of RTA. ASMs prescription in patients with identified risk factors of RTA should be considered with caution. Study number: ClinicalTrials.gov , NCT04480996.