Therapie最新文献

Importance: The safety profile of a rechallenge with BRAF inhibitors (BRAFi) or a combination of BRAF and MEK inhibitors (MEKi) following an adverse drug reaction (ADR) remains largely unexplored.

Objective: To identify the reported recurrence rate of the same ADR after a BRAFi±MEKi targeted therapy (TT) rechallenge in patients with cancer and to identify factors associated with recurrence.

Design, setting, and participants: In this observational, pharmacovigilance study, ADR reports were sourced from VigiBase, the World Health Organization database. The inclusion criteria encompassed all BRAFi cases (with or without MEKi) through September 01, 2023, irrespective of the primary cancer diagnosis.

Main outcomes and measures: The primary outcome was the reported recurrence rate of the same initial ADR following TT rechallenge. Secondary outcomes measures included were identification of variables associated with recurrence among informative rechallenges, defined as those with known recurrence status.

Results: Out of 21,339 ADR cases linked to TT, 4771 (22.4%) reported a rechallenge, with 563 yielding informative data (11.8%). Recurrence of the initial ADR was reported in 223 cases, resulting in a reported recurrence rate of 39.6% (95% CI: 35.7-43.7). The highest recurrence rates in a rechallenge were observed for pyrexia (47%, 95% CI: 39-55), renal failure (46%, 95% CI: 32-60), and musculoskeletal disorders (44%, 95%CI: 33-56). There was no significant influence of factors such as TT regimen (either BRAFi monotherapy or any TT combination), age, sex, or the type of cancer on reported recurrence rate.

Conclusions and relevance: In real-world settings, approximately two-fifths of cases with notified TT rechallenges led to a reporting of recurrence of the same initial ADR. The primary determinant of reported recurrence seems to be the nature of the initial ADR rather than the TT regimen, or any other baseline patient characteristic.

Aim: During coronavirus disease 2019 (COVID-19), the incidence rate of adverse drug reactions (ADRs) in hospitalized patients seemed higher than before the pandemic. Severe inflammation triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was cited as an explanation. We aimed to determine whether COVID-19 infection was associated with a higher risk of ADRs compared to other infectious diseases.

Methods: A monocentric historic cohort, "exposed/unexposed" study, was conducted in the university hospital of Saint-Étienne (inclusion period from March 05, 2020 to April 16, 2020 for "COVID-19" and from January to December 2019 for "non-COVID-19"). All ADRs reported in patients' medical records were retrospectively assessed using Bégaud et al.'s algorithm. A multivariable Cox regression was performed to assess the hazard ratio (HR).

Results: The incidence rate of 4.64 ADRs per person-month in the "COVID-19" group did not differ from the 3.52 ADRs per person-month in the "non-COVID-19" group (multivariable adjusted HR 1.29, 95% confidence interval [CI], 0.91-1.81, P=0.1436). COVID-19 patients had more hepatobiliary disorders whereas non-COVID-19 patients had more renal and urinary disorders. Classes of drugs mostly involved in ADRs occurrence were antibiotics, followed by antithrombotics in both groups. Compared to patients with no ADR, patients with ADRs had higher C-reactive protein (CRP) levels and a lower estimated glomerular filtration rate (eGFR).

Conclusion: In this study, the incidence rate in hospitalized patients with COVID-19 was not statistically different from that in the group with another infection. High CRP levels, as well as low eGFR, were the main risk factors for the occurrence of ADRs and should be considered in further ADR prevention strategies.

Objective: A supply shortage of dronabinol occurred between December 2023 and February 2024, forcing chronic pain patients to discontinue this treatment. We assessed the impact of this shortage on patients in our hospital.

Method: A retrospective observational study of patients treated with dronabinol was conducted. Collected data included socio-demographic, pharmacological and clinical data. Pain intensity and its interference, the intensity of other pain dimensions (mood, relationship with others, etc.) and quality of sleep were collected before discontinuation (dronabinol dosage balanced, M0) and at the end of discontinuation (dronabinol stopped for several weeks, M3). The patient's perception of his state of health evolution was collected at the end of the shortage.

Results: Health deterioration was reported by 86% of patients after 3 months of rupture. Pain intensity and its interference with patients' daily lives increased significantly. Patients' sleep deteriorated significantly. The number of patients with permanent pain increased 5-fold (n=2 at M0 and n=10 at M3). The number of patients with more than 20 painful attacks per 24hours increased 2-fold (n=2 at M0 and n=4 at M3).

Conclusion: Although data on the efficiency of dronabinol are currently limited, this supply disruption has had negative clinical consequences for our patients. With drug shortages multiplying in recent years, the marketing of new specialties and therefore the availability of therapeutic alternatives could help reduce the clinical impact of a possible new dronabinol shortage in these refractory chronic pain patients.

Objective: Metformin-associated lactic acidosis (MALA) is a rare but serious adverse drug reaction (ADR). The aim of the study was to identify clinical situations associated with the onset of MALA in patients hospitalised in the Nord Pas de Calais regional intensive care units (ICUs), and to assess its preventability.

Material and methods: We included all cases of MALA, identified by metformin accumulation >2.3mg/dL and lactate >2.2mmol/L, reported by the regional ICU physicians to the Regional Centre of Pharmacovigilance and registered in the French Pharmacovigilance Database between 1 January 2017 and 30 December 2018.

Results: One hundred and ninety-eight (198) cases of MALA were included. 38 patients died in direct association with MALA (19.2%). There was a correlation between metformin plasma accumulation and acute renal failure and with the severity of MALA (P<0.0001). All patients presented an acute intercurrent event favouring MALA, dehydration for 87 (43.9%) patients, severe infection for 65 (32.8%) patients. For 172 patients (86.7%), the prescription was not adapted to the intercurrent medical situation as recommended. Seventy (40.5%) patients consulted their general practitioner for the acute intercurrent event, 1 temporarily stopped metformin and 34.3% had been referred directly to hospital. The remaining 65.7% presented to the hospital around 4 days later due to worsening symptoms. MALA was identified as preventable in 160 patients (80.8%).

Conclusions: MALA in ICUs often follow acute dehydration or infection, and these high-risk situations must be signals to prevent this serious ADR. Specific education programmes for physicians and patients could also reduce this risk.

4P medicine (personalized, preventive, predictive, and participatory) is experiencing a remarkable rise, and pharmacogenetics is an essential part of it. However, several obstacles are hindering its deployment. This round table brought together a group of experts to take stock of the situation, reflecting on ways to facilitate the prescription of these tests and the dissemination of the results on a national scale. The experts looked at the methods of prescribing and communicating pharmacogenetic data in the current situation as well as in the coming years, with the arrival of artificial intelligence software. The questions relating to the reimbursement of tests - as topical as ever - were also discussed, as this is a way to allow all patients to access these tests. Numerous recommendations have been formulated on these various points, aimed at facilitating prescription management for healthcare professionals, and ensuring the retention and use of the results throughout the patient's life. Finally, better patient information was recommended, as well as strengthening the involvement of healthcare professionals and industry stakeholders in this process, with insistence on the necessary training and commitment to ensure its success.

France has been engaged in a legal and organisational transition for many years. It has had to adapt its national framework to the legal requirements of personal data protection, European ambitions and international competition. From the Data Protection Act of 1978 to the Healthcare System Transformation Act of 2019, reforms have strengthened requirements in terms of personal data protection, while opening the way to innovative uses. Recent European regulations, such as the AI Act (2024) and the European Health Data Area (2024), aim to reinforce this dynamic, ensuring a secure, transparent and competitive framework for the sharing and use of health data. How can we ensure that the re-use of healthcare data is truly effective, while respecting the fundamental rights of citizens? How can we reconcile national and European ambitions with the technical and organisational realities of the healthcare system, in clinical and research teams, and as close as possible to patients and users in our territories? These questions are essential, because access to and use of health data are seen as major levers for improving the quality of care, supporting innovation and boosting the competitiveness of the French healthcare system. The impact study on the 2019 reform stresses that the transformation of the healthcare system will have to be based on taking better account of the needs of patients and professionals by encouraging local initiatives. In this context, France faces a priority to establish greater coordination between the national and local levels, while preserving the trust of users. This precious trust is essential if we are to make the transition to achieving national and European objectives for the scientific and economic use of data.

The drug authorization process is shifting towards a policy aimed at shortening time-to-market. While this policy facilitates early access to new treatments, it can also result in potentially insufficient knowledge of both efficacy and safety at the time of marketing. The latter is particularly true for long-term outcomes or in specific populations (e.g., children and the elderly). Yet, French pharmacoepidemiology is currently not designed to address these challenges, despite recognized expertise. In this context, we aim: (i) to define a strategy for strengthening pharmacoepidemiology in France; and (ii) to identify the associated human, technical, and financial requirements to ensure its success. In this paper, we present the French Pharmacoepidemiology Initiative (https://frenchpharmacoepi.org/), i.e. a network of independent academic teams to complement existing institutions. It will provide coordinated expertise and a workforce to meet national and regional needs for pharmacoepidemiological monitoring and drug-related decision-making. Leveraging the existing expertise of university hospital pharmacoepidemiology units would enable rapid operational deployment to inform the decisions and policies of national regulatory agencies.