Lille Inflammation Research International Center

Vedolizumab has become the preferred first-line advanced therapy in ulcerative colitis (UC). However, the optimal second-line treatment following vedolizumab failure remains unclear. We aimed to evaluate the effectiveness and safety of second-line therapies after first-line vedolizumab. We conducted a multicenter retrospective study including UC patients from 31 centers who received infliximab (IFX), subcutaneous (SC) anti-TNFs, or ustekinumab after vedolizumab failure. The primary endpoint was steroid-free clinical remission (SFCR) at week 14. Predictors of remission were identified using multivariate logistic regression. Among 196 patients, 99 received IFX, 27 anti-TNF SC, and 70 ustekinumab. At week 14, SFCR was achieved in 78 patients (39.8%): 38 (38.4%) with IFX, 8 (29.6%) with anti-TNF SC, and 32 (45.7%) with ustekinumab, with no significant difference between groups (p=0.32). Median treatment persistence ranged from 8 to 9.2months. Baseline corticosteroid use was associated with lower odds of SFCR (OR=0.37, 95% CI [0.18-0.73]). Adverse events occurred in 15.8% of patients, including 12.2% serious events. Overall adverse events were less frequent with ustekinumab than with IFX (10.0% vs. 24.2%, p=0.02), while serious events were comparable (5.7% vs. 16.1%, p=0.08). Discontinuation due to adverse events was more frequent with IFX (12.1%) and anti-TNF SC (14.8%) than with ustekinumab (2.9%, p=0.045 and 0.049). In UC patients failing vedolizumab, second-line IFX, anti-TNF SC, and ustekinumab showed similar effectiveness and persistence. Infliximab remains a robust option for rapid control in high inflammatory burden, whereas ustekinumab may be preferred for its superior safety profile in high-risk patients.

Abstract Objective Hereditary angioedema (HAE) is a rare disease that presents with recurrent attacks that can be triggered by stress or other emotions. The emotional impact of HAE is well-documented, although mainly via self-reported questionnaires. In this study, we used physiological measures to investigate stress regulation in patients with HAE and compared them to patients with immune thrombocytopenia (ITP), a disease that also progresses with attacks but without emotional triggers. Methods Twenty-six adult patients with HAE or ITP (13 each) were included in the study. Patients were asked to perform several computerized tasks that activated different branches of the autonomic nervous system (ANS). Heart rate variability and electrodermal activity were measured during the experimental tasks and a medical consultation that followed the experiments. Results Patients with HAE did not differ from patients with ITP in their physiological responses. In the reactivity tasks, a non-significant correlation significance was observed between reaction times (RTs) and peak spread in the HAE and ITP groups only for male patients and in a different way for HAE (negative correlation) and ITP (positive correlation). During medical consultations, an association between the physician’s perception of the patient’s stress and the patient’s physiological measures of stress was found only in female HAE patients, but without significance. Conclusions The ANS of patients with HAE and ITP was similarly and abnormally activated, with a possible effect by sex. These results shed new light on the role of emotional regulation in chronic diseases. Trial registration This article does not report the results of a health care intervention on human participants. The research was not preregistered in any registry. The analysis plan was not preregistered in an independent, institutional registry. Data, analytic methods, and study materials are not made directly available.

Recurrent isolated angioedema (AE) is a diagnostic and therapeutic challenge. Only a rigorous clinical approach can rule out the most obvious diagnoses. The recent international classification recognizes 7 subgroups: mast cells induced AE (spontaneous, allergic), Bradykinin mediated AE (Hereditary or acquired C1Inh; kallikrein-kinin mutations), HAE due to vascular endothelium dysfunction, drug induced AE and AE of unknow origin. Bradykinin-mediated hereditary angioedema (BK-HAE) are rare conditions. The currently accepted incidence of HAE-C1INH is approximately 1 in 50,000 inhabitants per year. Bradykinin is released following activation of the kallikrein/kinin pathway in the vascular lumen and is rapidly degraded by kininases, the main one being angiotensin-converting enzyme. The disease manifests as subcutaneous or submucosal edema. When an attack occurs in the pharynx/larynx area, there is a high risk of asphyxia (25% in the absence of specific treatment). This risk is unpredictable and exists throughout the patient's life. AE can be localized in the abdomen and resemble a surgical emergency. The disease is more symptomatic in women, as estrogen is an aggravating factor. In AE due to C1INH deficiency, the diagnosis is based on the search for a weight and/or functional deficiency in C1 inhibitor. In the forms with normal C1 inhibitor, the diagnosis is solely genetic, such as F12, PLG, or KNG1 mutations. The prognosis for these rare diseases has changed considerably in recent years with the arrival of new, highly effective specific drugs. Patient education is an important part of management. We present here the French protocol for the diagnosis and management of bradykinin-mediated hereditary AE.

IntroductionAllergic comorbidities are common in patients with atopic dermatitis (AD). Individual trials with abrocitinib or dupilumab demonstrated efficacy and safety in patients with moderate-to-severe AD and allergic comorbidities. This post hoc analysis of the phase 3 JADE COMPARE and DARE trials compared efficacy, safety, and quality of life following abrocitinib and dupilumab treatment in adults with moderate-to-severe AD, with or without comorbid asthma, allergic rhinitis, or food allergy.MethodsData were pooled from patients who received abrocitinib (200 mg/day) or dupilumab (300 mg/every 2 weeks) for 16 weeks with concomitant topical therapy. Assessments by self-reported asthma, allergic rhinitis, or food allergy included the proportion of patients achieving Investigator’s Global Assessment of clear or almost clear (IGA 0/1), ≥ 75% improvement in Eczema Area and Severity Index (EASI-75), ≥ 4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4), least squares mean change from baseline in Dermatology Life Quality Index (DLQI) and SCORing Atopic Dermatitis (SCORAD), and safety.ResultsOf 1195 patients (abrocitinib, n = 588; dupilumab, n = 607), 377 (32%), 225 (19%), and 211 (18%) patients self-reported comorbid asthma, food allergy, or allergic rhinitis, respectively. Week 16 IGA 0/1 responses were comparable between patients with/without comorbidity with abrocitinib (52%/54% [with/without asthma], 50%/54% [with/without allergic rhinitis], and 53%/53% [with/without food allergy]) or dupilumab (42%/42%, 37%/43%, and 47%/41%). EASI-75 and PP-NRS4 responses and DLQI and SCORAD improvements were also comparable between patients with/without comorbidity in each treatment arm. Treatment-emergent adverse events were more common in patients with comorbidities in the abrocitinib (76%/67% [with/without asthma], 80%/67% [with/without allergic rhinitis], and 78%/67% [with/without food allergy]) and dupilumab (71%/53%, 71%/57%, and 62%/59%) arms.ConclusionAbrocitinib and dupilumab improved AD signs and symptoms with a manageable safety profile in patients with moderate-to-severe AD, regardless of asthma, allergic rhinitis, or food allergy.Graphical available for this article.Trial RegistrationClinicalTrials.gov identifier, NCT03720470 (JADE COMPARE) and NCT04345367 (DARE).Graphical Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-025-01516-w.

BackgroundJunior doctors often demonstrate insufficient prescribing skills, highlighting the need to enhance undergraduate medical training in this area. Serious games (SGs) have proven effective in teaching knowledge and skills across various medical specialties including surgery and emergency care. To our knowledge, no SG specifically dedicated to prescribing has been developed to date. Our objective was to develop a new educational program, based on a learning game designed to enhance medical students’ competencies in safe and effective prescribing.ObjectiveThis study aimed to describe ADRENALINE, a learning game designed to promote safe and effective prescribing, and to report feedback from sixth-year undergraduate medical students at our medical school after the first year of its implementation in the therapeutics curriculum.MethodsThis study implemented an interactive educational program based on Kolb experiential learning theory to enhance safe and effective prescribing skills among sixth-year medical students. The program followed 3 phases: a preliminary in-person lecture introducing the SG ADRENALINE, autonomous gameplay, and a final debriefing lecture. ADRENALINE, accessible via university platform Moodle (Andrews Lyons) on multiple devices, was developed using MOSAIC software (Katia Quelennec), a software program created to develop evolutive SG based on real-life professional situations, and includes 20 realistic clinical scenarios of varying difficulty, requiring students to make therapeutic decisions and receive immediate feedback. Players advance through levels based on performance, with ongoing support from professors via feedback and a dedicated forum. The program was integrated into the therapeutic curriculum of Lille University, and participation was voluntary. All 598 sixth-year students were invited to access the game via email and to participate in pre- and postintervention surveys assessing usage patterns, satisfaction, and learning outcomes.ResultsBetween November 2023 and March 2024, 272 sixth-year students accessed the ADRENALINE program. Of these, 201/272 (73.9%) students completed at least one scenario and obtained scores ranging from 16.5 to 100 out of 100. Pretest survey responses (n=99 answers) indicated that 92/99 (93%) students identified as gamers and believed that SGs could be relevant for their medical education. Posttest survey responses (n=50 answers) reflected a high level of satisfaction among participants. Most students reported that ADRENALINE helps them apply academic knowledge in real-world context, feel more confident with prescribing and managing adverse drug reactions, improve their prescribing skills, and better prepare for the national Objective Structured Clinical Examination.ConclusionsWe developed a learning game focused on medical prescribing, designed to be easily shared with other French-speaking medical schools. Although only 201/598 (33.6%) students engaged with this initial version, 85% (42/50) of the feedback received was positive, indicating strong student interest and supporting the educational value of a game-based approach to enhance prescribing skills among undergraduate medical students.

Severe asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP) are airway diseases mostly caused by type 2 (T2) inflammation, in which eosinophils play an important role [1]. Severe asthma is characterised by persistent symptoms despite high doses of corticosteroids, which can lead to long-term side effects [2]. Consequently, biologics have been developed, including those targeting eosinophils through interleukin-5 (IL-5) or its receptor. However, these therapies do not uniformly suppress eosinophil activity [3], suggesting heterogeneity among eosinophil populations and differential sensitivity to treatments. In atopic dermatitis, another T2 inflammatory disorder, we have previously demonstrated that blood eosinophils display unique surface markers compared to healthy individuals [4]. Therefore, this study aimed to determine whether circulating eosinophils in patients with severe asthma or CRSwNP display altered surface marker expression in comparison to healthy controls. Furthermore, we assessed whether specific surface markers correlate with diseases clinical features. The description and characteristics of the participants included in the study are presented in Table 1 and the Document S1. The levels of surface markers were examined by flow cytometry as described in the Document S1. Among the surface markers, CD123 and CD125 are critical receptors for interleukin-3 (IL-3) and IL-5 involved in eosinophil differentiation, migration and survival. We also analysed Siglec-8, a marker of mature eosinophils and mast cells that reduces eosinophil activity [5] and chemokine receptors, CCR3 and CRTH2, binding the eotaxins and prostaglandin D2, respectively. Additionally, we assessed adhesion molecules (CD44 and CD62-L) and eosinophil activation markers (CD63, CD69, CD137, HLA-DR). Among all analysed markers, only CD125 was significantly higher on eosinophils from patients with severe asthma and in patients with CRSwNP compared to healthy controls (Figure 1A and Data S1 Figure 1B). We then performed correlation analyses between surface marker levels and clinical features (Figure 1B,C). In severe asthma, higher levels of HLA-DR, CD69, and CD44 correlated with poorer asthma control, as determined by the Asthma Control Test (ACT) or the Asthma Control Questionnaire (ACQ-6). Furthermore, increased airflow limitation, assessed via the Forced Exhaled Volume in 1 s/forced vital capacity ratio (FEV1/FVC), was associated with increased CD123 on eosinophils. CD62-L expression inversely correlates with age at disease onset and fractional exhaled nitric oxide (FeNO), the latter of which indicates greater T2 airway inflammation in patients with low CD62-L (Figure 1B). However, unlike Mesnil et al. [6], we did not identify distinct eosinophil subsets based on CD62-L and CD123 in either patients or controls. The number of exacerbations, total serum IgE levels and inhaled corticosteroid dose did not show significant correlations (Figure S2A). In CRSwNP, CCR3 level inversely correlated with nasal polyp score (NPS), whereas CD63 showed a positive correlation (Figure 1C). These significant associations are further illustrated in Figure S2B. We also performed correlation analyses between surface marker expressions (Table S1). However, due to the limited sample size, we did not pursue more complex multivariate clustering approaches at this stage. In conclusion, this is a study analysing human blood eosinophil surface markers in patients with severe asthma and CRSwNP. Variability among participants and limited sample size may have restricted the number of statistically significant outcomes. However, we observed a high surface expression of CD125 in severe asthma and CRSwNP compared to controls. This finding highlights the potential of using eosinophil phenotyping to identify patients who may respond to anti-IL-5 and IL-5 receptor therapy despite a moderate eosinophil count. Furthermore, we identified specific eosinophil surface markers (i.e., HLA-DR, CD69, CD44, CCR3) correlated with phenotypic and treatable traits (ACT, ACQ-6, NPS), providing potential biomarkers of airway diseases. Further research is needed to confirm the utility of eosinophil surface protein profiling in predicting disease features and therapeutic response. All authors have contributed significantly to the study. C. Chenivesse declares research grants from AstraZeneca, GSK, Santelys, and Novartis; personal fees from ALK-Abello, AstraZeneca, Boehringer-Ingelheim, Celtrion, Chiesi, Sanofi, and GSK; and congress support from AstraZeneca, Boehringer Ingelheim, Chiesi, Sanofi, and Novartis. G. Lefèvre received consulting fees, personal fees for advisory boards or meetings, and research funding from AstraZeneca and GSK. The rest of the authors declare that they have no relevant conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. Data S1: all70001-sup-0001-DataS1.zip. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.