Mepolizumab and benralizumab in patients with severe asthma and a history of eosinophilic granulomatosis with polyangiitis

IntroductionAsthma associated with eosinophilic granulomatosis with polyangiitis (EGPA) is often severe and corticosteroid-dependent, leading to significant morbidity. Mepolizumab and benralizumab are humanized monoclonal antibodies targeting interleukin 5 (IL-5) and its receptor, respectively. They have been shown to be effective in steroid-sparing in patients with severe eosinophilic asthma.ObjectiveOur aim was to evaluate the efficacy and safety of mepolizumab and benralizumab prescribed for severe asthma in patients with EGPA under “real-world” conditions.MethodsThis was a retrospective analysis of patients with EGPA and persistent asthma who received either mepolizumab 100 or 300 mg administered every 4 weeks, or benralizumab 30 mg administered every 4 weeks for the initial 3 injections and followed by an injection every 8 weeks thereafter, whilst combined with oral glucocorticoids. The follow-up every 6 ± 3 months included an assessment of clinical manifestations, pulmonary function tests and eosinophil cell count. The primary outcome was the proportion of patients at 12 months receiving a daily oral dose of prednisone or equivalent of 4 mg or less with a BVAS of 0.ResultsTwenty-six patients were included. After 12 months of treatment with mepolizumab or benralizumab, 32% of patients met the primary outcome and were receiving less than 4 mg of prednisone per day with a BVAS of 0. The median dose of prednisone was 10 mg per day at baseline, 9 mg at 6 months, and 5 mg at 12 months (p ≤ 0.01). At 12 months, 23% of patients were weaned off corticosteroids, while an increase or no change in dose was observed in 27% of patients. The median eosinophil count was significantly reduced from 365 cells/mm3 to 55 cells/mm3 at 6 months and 70 cells/mm3 at 12 months, respectively. No significant change was observed in FEV1. After 12 months of treatment, 14% of patients had had an average of 1 exacerbation of asthma, compared with 52% of patients before baseline. The tolerability profile was favorable.ConclusionIn this real-world study in patients with severe asthma and a history of EGPA asthma, mepolizumab and benralizumab had a significant steroid-sparing effect and reduced asthma exacerbation, but no significant effect on lung function

Maladie de Still de l'adulte (manifestations, traitements, évolution et facteurs pronostiques chez 57 patients)

Le but de cette étude observationnelle rétrospective est de décrire une cohorte française de maladies de Still de l'adulte (MSA) et d'en identifier les facteurs pronostiques. Les patients devaient remplir les critères de classification de Yamaguchi ou Fautrel à l'inclusion. Les variables candidates ont été analysées en régression multivariée non ajusté puis ajusté sur les variables potentiellement confondantes. Cinquante-sept patients sont suivis en moyenne 8,4 ans en médecine interne (75%) ou rhumatologie (25%). Le délai diagnostic médian est de 4 mois. L'évolution est monocyclique chez 17 patients, intermittente chez 25 et chronique chez 15. Le dosage de la ferritine glycosylée (FG) réalisé chez 37 patients est corrélé à un diagnostic plus précoce. Neuf 18FDG-PET scanners montrent un hypermétabolisme des tissus lymphatiques et glandulaires. Les complications, dont le syndrome d'activation lymphohistiocytaire (n=8), sont fréquentes (n=19). Aucun des trois décès répertoriés n'est attribuable à la MSA. La corticodépendance, prédite par une FG basse, concerne 23 patients (45%). Un quart des patients a reçu des anti-TNFa ou de l'anakinra, bien tolérés. La fièvre > 39,5C est prédictive d'une évolution monocyclique de la MSA alors que les arthrites et la thrombopénie sont respectivement associées à une évolution chronique et compliquée de la maladie. Les patients les plus jeunes sont les plus à risque de résistance aux premières lignes de traitement. La MSA reste de diagnostic difficile, sa mortalité est faible malgré des complications fréquentes. La FG et le 18FDG-PET scanner sont utiles pour le diagnostic. Les patients initialement très symptomatiques évolueront vers une forme systémique de MSA alors que ceux présentant seulement des arthrites évolueront vers une forme articulaire chronique.LYON1-BU Santé (693882101) / SudocSudocFranceF

Still’s Disease Mortality Trends in France, 1979–2016: A Multiple-Cause-of-Death Study

International audienceStill’s disease (SD) is often considered a benign disease, with low mortality rates. However, few studies have investigated SD mortality and its causes and most of these have been single-center cohort studies. We sought to examine mortality rates and causes of death among French decedents with SD. We performed a multiple-cause-of-death analysis on data collected between 1979 and 2016 by the French Epidemiological Center for the Medical Causes of Death. SD-related mortality rates were calculated and compared with the general population (observed/expected ratios, O/E). A total of 289 death certificates mentioned SD as the underlying cause of death (UCD) (n = 154) or as a non-underlying causes of death (NUCD) (n = 135). Over the study period, the mean age at death was 55.3 years (vs. 75.5 years in the general population), with differences depending on the period analyzed. The age-standardized mortality rate was 0.13/million person-years and was not different between men and women. When SD was the UCD, the most frequent associated causes were cardiovascular diseases (n = 29, 18.8%), infections (n = 25, 16.2%), and blood disorders (n = 11, 7.1%), including six cases (54%) with macrophage activation syndrome. As compared to the general population, SD decedents aged <45 years were more likely to die from a cardiovascular event (O/E = 3.41, p < 0.01); decedents at all ages were more likely to die from infection (O/E = 7.96–13.02, p < 0.001)

Still’s Disease Mortality Trends in France, 1979–2016: A Multiple-Cause-of-Death Study

Still’s disease (SD) is often considered a benign disease, with low mortality rates. However, few studies have investigated SD mortality and its causes and most of these have been single-center cohort studies. We sought to examine mortality rates and causes of death among French decedents with SD. We performed a multiple-cause-of-death analysis on data collected between 1979 and 2016 by the French Epidemiological Center for the Medical Causes of Death. SD-related mortality rates were calculated and compared with the general population (observed/expected ratios, O/E). A total of 289 death certificates mentioned SD as the underlying cause of death (UCD) (n = 154) or as a non-underlying causes of death (NUCD) (n = 135). Over the study period, the mean age at death was 55.3 years (vs. 75.5 years in the general population), with differences depending on the period analyzed. The age-standardized mortality rate was 0.13/million person-years and was not different between men and women. When SD was the UCD, the most frequent associated causes were cardiovascular diseases (n = 29, 18.8%), infections (n = 25, 16.2%), and blood disorders (n = 11, 7.1%), including six cases (54%) with macrophage activation syndrome. As compared to the general population, SD decedents aged &lt;45 years were more likely to die from a cardiovascular event (O/E = 3.41, p &lt; 0.01); decedents at all ages were more likely to die from infection (O/E = 7.96–13.02, p &lt; 0.001).</jats:p

Still’s Disease Mortality Trends in France, 1979–2016: A Multiple-Cause-of-Death Study

Still’s disease (SD) is often considered a benign disease, with low mortality rates. However, few studies have investigated SD mortality and its causes and most of these have been single-center cohort studies. We sought to examine mortality rates and causes of death among French decedents with SD. We performed a multiple-cause-of-death analysis on data collected between 1979 and 2016 by the French Epidemiological Center for the Medical Causes of Death. SD-related mortality rates were calculated and compared with the general population (observed/expected ratios, O/E). A total of 289 death certificates mentioned SD as the underlying cause of death (UCD) (n = 154) or as a non-underlying causes of death (NUCD) (n = 135). Over the study period, the mean age at death was 55.3 years (vs. 75.5 years in the general population), with differences depending on the period analyzed. The age-standardized mortality rate was 0.13/million person-years and was not different between men and women. When SD was the UCD, the most frequent associated causes were cardiovascular diseases (n = 29, 18.8%), infections (n = 25, 16.2%), and blood disorders (n = 11, 7.1%), including six cases (54%) with macrophage activation syndrome. As compared to the general population, SD decedents aged &lt;45 years were more likely to die from a cardiovascular event (O/E = 3.41, p &lt; 0.01); decedents at all ages were more likely to die from infection (O/E = 7.96–13.02, p &lt; 0.001)

Adult-onset Still's disease

AbstractFirst described in 1971, adult-onset Still's disease (AOSD) is a rare multisystemic disorder considered as a complex (multigenic) autoinflammatory syndrome.A genetic background would confer susceptibility to the development of autoinflammatory reactions to environmental triggers. Macrophage and neutrophil activation is a hallmark of AOSD which can lead to a reactive hemophagocytic lymphohistiocytosis. As in the latter disease, the cytotoxic function of natural killer cells is decreased in patients with active AOSD. IL-18 and IL-1β, two proinflammatory cytokines processed through the inflammasome machinery, are key factors in the pathogenesis of AOSD; they cause IL-6 and Th1 cytokine secretion as well as NK cell dysregulation leading to macrophage activation.The clinico-biological picture of AOSD usually includes high spiking fever with joint symptoms, evanescent skin rash, sore throat, striking neutrophilic leukocytosis, hyperferritinemia with collapsed glycosylated ferritin (<20%), and abnormal liver function tests.According to the clinical presentation of the disease at diagnosis, two AOSD phenotypes may be distinguished: i) a highly symptomatic, systemic and feverish one, which would evolve into a systemic (mono- or polycyclic) pattern; ii) a more indolent one with arthritis in the foreground and poor systemic symptomatology, which would evolve into a chronic articular pattern.Steroid- and methotrexate-refractory AOSD cases benefit now from recent insights into autoinflammatory disorders: anakinra seems to be an efficient, well tolerated, steroid-sparing treatment in systemic patterns; tocilizumab seems efficient in AOSD with active arthritis and systemic symptoms while TNFα-blockers could be interesting in chronic polyarticular refractory AOSD