; for the CORIMUNO-19 Collaborative Group IMPORTANCE Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19). OBJECTIVE To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia. DESIGN, SETTING, AND PARTICPANTS This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes. INTERVENTIONS Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants. MAIN OUTCOMES AND MEASURES Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events. RESULTS Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21). CONCLUSIONS AND RELEVANCE In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care...

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell–driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert‐guided and evidence‐based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Background: Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials. Objective:We sought to assess the effectiveness and safety of dupilumab in adults with AD in a real-life French multicenter retrospective cohort.Methods: Patients were included between March 2017 and April 2018. Efficacy outcomes were collected both at baseline and three months (M3), when available, including SCORAD (Scoring Atopic Dermatitis) and EASI (Eczema Area and Severity Index) scores. Adverse events (AE) were recorded at the follow-up. Results:We included 241 patients. The median follow-up time was 3.8±3.7 months. SCORAD75 and EASI75 were achieved in 27/163 (16.6%) and 40/82 (48.8%) patients, respectively. The median SCORAD and EASI at M3 were significantly lower compared with baseline (25±21 vs 56±27.4, p<10 -9 and 4.1±6.8 vs 17.9±15.4, p<10 -9 , respectively).Conjunctivitis was reported in 84/241 (38.2%) patients. The proportion of eosinophilia (>500/mm 3 ) during follow-up (57%) was higher than at baseline (33.7%) (n=172, p<10 -6 ).Dupilumab was stopped in 42 cases, 27 of which were due to an AE. Limitations:No control group, missing data. Conclusion:This real-life study demonstrated results similar to clinical trials, with regard to dupilumab effectiveness, but revealed a higher frequency of conjunctivitis and eosinophilia.

Background Patients with COVID-19 pneumonia have an excess of inflammation and increased concentrations of cytokines including interleukin-1 (IL-1). We aimed to determine whether anakinra, a recombinant human IL-1 receptor antagonist, could improve outcomes in patients in hospital with mild-to-moderate COVID-19 pneumonia.Methods In this multicentre, open-label, Bayesian randomised clinical trial (CORIMUNO-ANA-1), nested within the CORIMUNO-19 cohort, we recruited patients from 16 University hospitals in France with mild-to-moderate COVID-19 pneumonia, severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time RT-PCR, requiring at least 3 L/min of oxygen by mask or nasal cannula but without ventilation assistance, a score of 5 on the WHO Clinical Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the intensive care unit at admission to hospital. Eligible patients were randomly assigned (1:1) using a web-based secure centralised system, stratified by centre and blocked with varying block sizes (randomly of size two or four), to either usual care plus anakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) or usual care alone. Usual care was provided at the discretion of the site clinicians. The two coprimary outcomes were the proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 on the WHO-CPS) and survival without need for mechanical or non-invasive ventilation (including high-flow oxygen) at day 14. All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT04341584, and is now closed to accrual. FindingsBetween April 8 and April 26, 2020, we screened 153 patients. The study was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: 59 were assigned to the anakinra group, and 57 were assigned to the usual care group. Two patients in the usual care group withdrew consent and were not analysed. In the analysable population, the median age was 66 years (IQR 59 to 76) and 80 (70%) participants were men. In the anakinra group, 21 (36%) of 59 patients had a WHO-CPS score of more than 5 at day 4 versus 21 (38%) of 55 in the usual care group (median posterior absolute risk difference [ARD] -2•5%, 90% credible interval [CrI] -17•1 to 12•0), with a posterior probability of ARD of less than 0 (ie, anakinra better than usual care) of 61•2%. At day 14, 28 (47%; 95% CI 33 to 59) patients in the anakinra group and 28 (51%; 95% CI 36 to 62) in the usual care group needed ventilation or died, with a posterior probability of any efficacy of anakinra (hazard ratio [HR] being less than 1) of 54•5% (median posterior HR 0•97; 90% CrI 0•62 to 1•52). At day 90, 16 (27%) patients in the anakinra group and 15 (27%) in the usual care group had died. Serious adverse events occurred in 27 (46%) patients in the anakinra group and 21 (38%) in the usu...

Dipeptidyl peptidase-4 inhibitors have been suspected to induce bullous pemphigoid (BP). The objective of this study was to compare the observed frequency of gliptin intake in a large sample of 1,787 BP patients diagnosed between 2012 and 2015 in France, with the expected frequency after indirect age standardization on 225,412 individuals extracted from the database of the National Healthcare Insurance Agency. The secondary objective was to assess the clinical characteristics and the course of gliptin-associated BP, depending on whether gliptin was continued or stopped. The observed frequencies of intake of the whole gliptin class and that of vildagliptin in the BP population were higher than those in the general population after age standardization (whole gliptin class: 6.0%; 95% confidence interval ¼ 4.9e7.1% vs. 3.6%, observed-to-expected drug intake ratio ¼ 1.7; 95% confidence interval ¼ 1.4e2.0; P < 0.0001; vildagliptin ¼ 3.3%; 95% confidence interval ¼ 2.5e4.1% vs. 0.7%, ratio ¼ 4.4; 95% confidence interval ¼ 3.5e5.7; P < 0.0001). The association of any gliptinþmetformin was also higher than in the general population, ratio ¼ 1.8 (95% confidence interval ¼ 1.3e2.4; P < 0.0001). Gliptin-associated BP had no specific clinical characteristics. Gliptin was stopped in 48 (45.3%) cases. Median duration to achieve disease control, rate, and delay of relapse were not different whether gliptin was stopped or continued. This study strongly supports the association between gliptin intake, particularly vildagliptin, and the onset of BP.

Objective To assess the association between early and prolonged β blocker treatment and mortality after acute myocardial infarction.Design Multicentre prospective cohort study.Setting Nationwide French registry of Acute ST- and non-ST-elevation Myocardial Infarction (FAST-MI) (at 223 centres) at the end of 2005.Participants 2679 consecutive patients with acute myocardial infarction and without heart failure or left ventricular dysfunction.Main outcome measures Mortality was assessed at 30 days in relation to early use of β blockers (≤48 hours of admission), at one year in relation to discharge prescription, and at five years in relation to one year use.Results β blockers were used early in 77% (2050/2679) of patients, were prescribed at discharge in 80% (1783/2217), and were still being used in 89% (1230/1383) of those alive at one year. Thirty day mortality was lower in patients taking early β blockers (adjusted hazard ratio 0.46, 95% confidence interval 0.26 to 0.82), whereas the hazard ratio for one year mortality associated with β blockers at discharge was 0.77 (0.46 to 1.30). Persistence of β blockers at one year was not associated with lower five year mortality (hazard ratio 1.19, 0.65 to 2.18). In contrast, five year mortality was lower in patients continuing statins at one year (hazard ratio 0.42, 0.25 to 0.72) compared with those discontinuing statins. Propensity score and sensitivity analyses showed consistent results.Conclusions Early β blocker use was associated with reduced 30 day mortality in patients with acute myocardial infarction, and discontinuation of β blockers at one year was not associated with higher five year mortality. These findings question the utility of prolonged β blocker treatment after acute myocardial infarction in patients without heart failure or left ventricular dysfunction.Trial registration Clinical trials NCT00673036.

Background Anaphylaxis, which is rare, has been reported after COVID‐19 vaccination, but its management is not standardized. Method Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre‐vaccination screening and management of allergic reactions to COVID‐19 vaccines, and literature was analysed. Results No death due to anaphylaxis to COVID‐19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine are excipients. The authors propose allergy evaluation of persons with the following histories: 1—anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2—anaphylaxis to oral/topical PEG containing products; 3—recurrent anaphylaxis of unknown cause; 4—suspected or confirmed allergy to any mRNA vaccine; and 5—confirmed allergy to PEG or derivatives. We recommend a prick‐to‐prick skin test with the left‐over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable. Conclusions These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID‐19 vaccines and enable more people with history of allergy to be vaccinated.

Introduction The COVID‐19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown. Aim To understand how CU patients are affected by the COVID‐19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID‐19. Materials and Methods Our cross‐sectional, international, questionnaire‐based, multicenter UCARE COVID‐CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences. Results The COVID‐19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID‐19 patient care, which negatively impacted on the care of urticaria patients. The rate of face‐to‐face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID‐19, but COVID‐19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID‐19. Conclusions The COVID‐19 pandemic brings major changes and challenges for CU patients and their physicians. The long‐term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.