Tolerance and efficacy of targeted therapies prescribed for off-label indications in refractory systemic autoimmune diseases: data of the first 100 patients enrolled in the TATA registry (TArgeted Therapy in Autoimmune Diseases).

OBJECTIVES: To assess the tolerance and efficacy of targeted therapies prescribed off-label in refractory low-prevalence autoimmune and inflammatory systemic diseases. METHODS: The TATA registry (TArgeted Therapy in Autoimmune Diseases) is a prospective, observational, national and independent cohort follow-up. The inclusion criteria in the registry are as follows: age >18 years; low-prevalence autoimmune and inflammatory systemic disease treated with off-label drugs started after 1 January 2019. RESULTS: Hundred (100) patients (79 women) were enrolled. The median age was 52.5 years (95% CI 49 to 56) and the median disease duration before enrolment was 5 years (3 to 7). The targeted therapies at enrolment were as follows: Janus kinase/signal transducers and activators of transcription inhibitors (44%), anti-interleukin (IL)-6R (22%), anti-IL-12/23, anti-IL-23 and anti-IL-17 (9%), anti-B cell activating factor of the tumour necrosis factor family (5%), abatacept (5%), other targeted treatments (9%) and combination of targeted treatments (6%). 73% of patients were receiving corticosteroid therapy at enrolment (median dose 10 mg/day). The current median follow-up time is 9 months (8 to 10).Safety: 11 serious infections (incidence rate of 14.8/100 patient-years) and 1 cancer (1.3 cancers/100 patient-years) were observed. Two patients died from severe COVID-19 (2.7 deaths/100 patient-years).Efficacy: the targeted treatment was considered effective by the clinician in 56% of patients and allowed, in responders, a median reduction of oral corticosteroids of 15 (9 to 21) mg/day, below 7.5 mg/day in 76% of patients, while 28% discontinued. CONCLUSION: These initial results of the TATA registry confirm the diversity of targeted treatments prescribed off-label in refractory autoimmune diseases and their corticosteroid-sparing effect when effective. Tolerance was acceptable in these refractory patients with a long history of treatment with immunosuppressive drugs.

Effective Anti-SARS-CoV-2 Immune Response in Patients With Clonal Mast Cell Disorders.

BACKGROUND: Mast cells are key players in innate immunity and the TH2 adaptive immune response. The latter counterbalances the TH1 response, which is critical for antiviral immunity. Clonal mast cell activation disorders (cMCADs, such as mastocytosis and clonal mast cell activation syndrome) are characterized by abnormal mast cell accumulation and/or activation. No data on the antiviral immune response in patients with MCADs have been published. OBJECTIVE: To study a comprehensive range of outcomes in patients with cMCAD with PCR- or serologically confirmed coronavirus disease 2019 and to characterize the specific anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune response in this setting. METHODS: Clinical follow-up and outcome data were collected prospectively over a 12-month period by members of the French Centre de Référence des Mastocytoses rare disease network. Anti-SARS-CoV-2-specific T-cell activity was measured with an ELISA, and humoral responses were evaluated by assaying circulating levels of specific IgG, IgA, and neutralizing antibodies. RESULTS: Overall, 32 patients with cMCAD were evaluated. None required noninvasive or mechanical ventilation. Two patients were admitted to hospital for oxygen and steroid therapy. The SARS-CoV-2-specific immune response was characterized in 21 of the 32 patients. Most had high counts of circulating SARS-CoV-2-specific, IFN-γ-producing T cells and high titers of neutralizing antispike IgGs. The patients frequently showed spontaneous T-cell IFN-γ production in the absence of stimulation; this production was correlated with basal circulating tryptase levels (a marker of the mast cell burden). CONCLUSIONS: Patients with cMCADs might not be at risk of severe coronavirus disease 2019, perhaps due to their spontaneous production of IFN-γ.

Immunothérapie dans le mélanome en hospitalisation à domicile : enquête de satisfaction et retour d’expérience des centres français d’oncodermatologie

Introduction Le nombre de patients atteints de mélanome traités par anti-PD1 en HDJ augmente ces dernières années en raison de l’avènement des traitements adjuvants. L’épidémie du COVID-19 a bouleversé l’organisation des HDJ par la déprogrammation de certaines cures, la diminution du personnel soignant en HDJ et la nécessité de limiter les infections nosocomiales COVID-19. Ce contexte sanitaire inédit a motivé la mise en place d’une filière HDJ-HAD permettant la réalisation des perfusions d’immunothérapie à domicile. Matériel et méthodes Dans le but d’évaluer le parcours mis en place ainsi que cette pratique à l’échelle nationale, nous menons un travail en 2 parties : – la première multicentrique pour évaluer la pratique de l’immunothérapie en HAD avec un questionnaire auprès de différents centres français d’oncodermatologie, – la deuxième monocentrique avec l’inclusion des tous les patients ayant un mélanome traité actuellement ou ayant été traité par anti-PD1(adjuvant ou curatif) dans la filière HDJ-HAD au CHUGA et la distribution d’un questionnaire de satisfaction sur ce parcours HAD aux patients et aux différents intervenants de cette filière. Résultats Au niveau national sur 17 centres répondeurs, 3 pratiquent l’immunothérapie en HAD. Les principaux points positifs sur leurs retours d’expériences sont la satisfaction des patients et la libération de places en HDJ. Les principaux freins sont la diminution des chiffres d’activité de l’HDJ, la difficulté de gérer les toxicités à distance, et les problèmes de coordination entre l’HAD et la pharmacie centrale de l’hôpital. Nous avons inclus 27 patients au CHUGA (adjuvant n=13, curatif n=14). Plus de 90 % des patients sont très ou totalement satisfaits de la prise en charge en HAD et recommanderaient ce parcours de traitement à d’autres patients. Il en est de même pour les différents professionnels de santé, néanmoins il ressort un manque de formation sur l’immunothérapie et le mélanome pour les praticiens libéraux. Discussion La pandémie de COVID-19 a permis la mise en place d’une filière HDJ-HAD ou une augmentation de l’inclusion en HAD de patients sous anti-PD1 selon les centres. Une étude française montre des résultats concordants avec une moyenne de satisfaction cotée à 9 sur 10 [1]. Une seconde étude montre que l’immunothérapie en HAD est moins coûteuse qu’en HDJ pour la sécurité sociale [2]. À travers ce travail, nous essayerons de mieux structurer ce parcours qui sera poursuivi dans notre centre, et d’améliorer la collaboration ville-hôpital en proposant des formations aux intervenants libéraux.

COVID-19 as a trigger of acute attacks in people with hereditary angioedema.

Acute attacks could occur during the convalescent phase of COVID-19 illness, more commonly in patients with a history of frequent attacks. However it is unclear whether the acute attacks during the convalescent phase are specifically triggered by COVID-19 or not.

The global impact of the COVID-19 pandemic on the management and course of chronic urticaria.

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.