Delayed-Onset Hemolytic Anemia in Patients with Travel-Associated Severe Malaria Treated with Artesunate, France, 2011–2013

French Artesunate Working GroupInternational audienceArtesunate is the most effective treatment for severe malaria. However, delayed-onset hemolytic anemia has been observed in ≈20% of travelers who receive artesunate, ≈60% of whom require transfusion. This finding could discourage physicians from using artesunate. We prospectively evaluated a cohort of 123 patients in France who had severe imported malaria that was treated with artesunate; our evaluation focused on outcome, adverse events, and postartesunate delayed-onset hemolysis (PADH). Of the 123 patients, 6 (5%) died. Overall, 97 adverse events occurred. Among the 78 patients who received follow-up for >8 days after treatment initiation, 76 (97%) had anemia, and 21 (27%) of the 78 cases were recorded as PADH. The median drop in hemoglobin levels was 1.3 g/dL; 15% of patients with PADH had hemoglobin levels of <7 g/dL, and 1 required transfusion. Despite the high incidence of PADH, the resulting anemia remained mild in 85% of cases. This reassuring result confirms the safety and therapeutic benefit of artesunate

Demographic and Clinical Factors Associated with Response to Smallpox Vaccine in Preimmunized Volunteers

CONTEXT: In March 2003, the French Ministry of Health implemented a program on preparedness and response to a biological attack using smallpox as weapon. This program included the establishment of a preoutbreak national team that could be revaccinated against smallpox. OBJECTIVE: To identify demographic and clinical factors associated with vaccination success defined as the presence of a pustule at the inoculation site at day 8 (days 7-9), with an undiluted vaccinia virus derived from a Lister strain among preimmunized volunteers. VOLUNTEERS AND METHODS: From March 2003 to November 2006, we have studied prospectively 226 eligible volunteers. Demographic data were recorded for each volunteer (age, sex, number of previously smallpox vaccinations and date of the last vaccination). Smallpox vaccine adverse reactions were diagnosed on the basis of clinical examination performed at days 0, 7, 14, 21 and 28 after revaccination. RESULTS: A total of 226 volunteers (sex ratio H/F = 2.7) were revaccinated. Median age was 45 years (range: 27-63 yrs). All volunteers completed follow-up. Median number of vaccinations before revaccination was 2 (range: 1-8). The median delay between time of the study and the last vaccination was 29 years (range; 18-60 yrs). Sixty-one volunteers (27%) experienced one (n = 40) or more (n = 21) minor side effects during the 2-14 days after revaccination. Successful vaccination was noted in 216/226 volunteers (95.6%) at day 8 and the median of the pustule diameter was 5 mm (range: 1-20 mm). Size of the pustule at day 8 was correlated with age (p = 0.03) and with the presence of axillary adenopathy after revaccination (p = 0.007). Sex, number of prior vaccinations, delay between the last vaccination and revaccination, and local or systemic side effects with the exception of axillary adenopathy, were not correlated with the size of the pustule at day 8. CONCLUSIONS: Previously vaccinated volunteers can be successfully revaccinated with the Lister strain

L’organisation de la pharmacovigilance en France, en Europe et dans le monde

Recevoir un nouveau médicament pour soigner une maladie rare signifie aussi en connaitre potentiellement les effets secondaires, qu’ils soient déjà connus ou pas encore. Leur signalement intéresse au plus haut point les équipes de pharmacovigilance, dont le rôle consiste à surveiller de près la pharmacopée et à prévenir le risque d’événements indésirables qui résultent de son utilisation. Gros plan sur une discipline à l’image souvent malmenée

Toxidermies sous anti-vitamine K (revue de la littérature et analyse des cas graves de la base française de pharmacovigilance)

Les anti-vitamine K (AVK) appartiennent à 2 familles chimiques: les coumariniques (acénocoumarol et warfarine) et les indane-diones (fluindione). La littérature rapporte plus d'effets immuno-allergiques (IA) sous indane-diones que sous coumariniques. Pour comparer le risque IA de ces molécules, nous avons réalisé une étude rétrospective à partir des notifications de toxidermies graves sous AVK de la Base Nationale de PharmacoVigilance et à partir des estimations des effectifs de patients traités par AVK en France. Il n'y avait pas de différence significative des incidences annuelles moyennes de notifications de toxidermies graves IA et non IA entre les AVK. Cependant, la part de notifications de syndromes d'hypersensibilité parmi les toxidermies graves IA était plus importante sous fluindione (16,7%) que sous AVK coumariniques (4,5% et 2,9%), soulevant la question de la justification de la place occupée par cette molécule sur le marché des AVK en France (80% des prescriptions en 2007).TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Checkpoint inhibitor-associated immune arthritis

International audienceNo abstract availabl

Checkpoint inhibitor-associated immune arthritis

International audienceNo abstract availabl

Characterizing drug-induced capillary leak syndromes using the World Health Organization VigiBase

International audienc

Graft Versus Host Disease Associated with Immune Checkpoint Inhibitors: A Pharmacovigilance Study and Systematic Literature Review

International audienceBackground: In patients with allogenic hematopoietic stem cell transplantation (allo-HSCT), immune-checkpoint inhibitors (ICI) are used to treat malignancy recurrence. However, ICI are also associated with graft vs. host disease (GVHD). In this pharmacovigilance analysis, we aimed to characterize cases of GVHD associated with ICI, drawn from the World Health Organization pharmacovigilance database, VigiBase®, and from literature.Methods: We performed VigiBase® query of cases of GVHD associated with ICI. These cases were combined with those of literature, not reported in VigiBase®. The Bayesian estimate of disproportionality analysis, the information component, was considered significant if its 95% credibility interval lower bound was positive; denoting a significant association between GVHD and the suspected ICI. Time to onset between ICI and GVHD onset and subsequent mortality were assessed.Results: Disproportionality analysis yielded 93 cases of GVHD associated with ICI (61.8% men, median age 38 [interquartile range = 27; 50] years). Cases were mostly associated with nivolumab (53/93, 57.0%), pembrolizumab (23/93, 24.7%) and ipilimumab (12/93, 12.9%) monotherapies. GVHD events occurred after 1 [1; 5.5] injection of ICI, with a time to onset of 35 [IQR = 14; 176] days. Immediate subsequent mortality after GVHD was 24/93, 25.8%. There was no significant difference in mortality depending on the molecule (p = 0.41) or the combination regimen (combined vs. monotherapy, p = 0.60). Previous history of GVHD was present in 11/18, 61.1% in cases reported in literature.Conclusion: In this worldwide pharmacovigilance study, disproportionality yielded significant association between GVHD and ICI, with subsequent mortality of 25.8%. Previous history of GVHD was reported in more than half of cases.Clinicaltrials.gov identifier:NCT0349224

Cytopenia induced by low-dose methotrexate: An analysis of 433 cases from the French pharmacovigilance database

International audienc