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

International audienceBackgroundMast 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.ObjectiveTo 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.MethodsClinical 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.ResultsOverall, 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).ConclusionsPatients with cMCADs might not be at risk of severe coronavirus disease 2019, perhaps due to their spontaneous production of IFN-γ

Intravenous versus subcutaneous tocilizumab in Takayasu arteritis: multicentre retrospective study

Objectives: In this large multicentre study, we compared the effectiveness and safety of tocilizumab intravenous versus subcutaneous (SC) in 109 Takayasu arteritis (TAK) patients.Methods: We conducted a retrospective multicentre study in referral centres from France, Italy, Spain, Armenia, Israel, Japan, Tunisia and Russia regarding biological-targeted therapies in TAK, since January 2017 to September 2019.Results: A total of 109 TAK patients received at least 3 months tocilizumab therapy and were included in this study. Among them, 91 and 18 patients received intravenous and SC tocilizumab, respectively. A complete response (NIH <2 with less than 7.5 mg/day of prednisone) at 6 months was evidenced in 69% of TAK patients, of whom 57 (70%) and 11 (69%) patients were on intravenous and SC tocilizumab, respectively (p=0.95). The factors associated with complete response to tocilizumab at 6 months in multivariate analysis, only age <30 years (OR 2.85, 95% CI 1.14 to 7.12; p=0.027) and time between TAK diagnosis and tocilizumab initiation (OR 1.18, 95% CI 1.02 to 1.36; p=0.034). During the median follow-up of 30.1 months (0.4; 105.8) and 10.8 (0.1; 46.4) (p<0.0001) in patients who received tocilizumab in intravenous and SC forms, respectively, the risk of relapse was significantly higher in TAK patients on SC tocilizumab (HR=2.55, 95% CI 1.08 to 6.02; p=0.033). The overall cumulative incidence of relapse at 12 months in TAK patients was at 13.7% (95% CI 7.6% to 21.5%), with 10.3% (95% CI 4.8% to 18.4%) for those on intravenous tocilizumab vs 30.9% (95% CI 10.5% to 54.2%) for patients receiving SC tocilizumab. Adverse events occurred in 14 (15%) patients on intravenous route and in 2 (11%) on SC tocilizumab.Conclusion: In this study, we confirm that tocilizumab is effective in TAK, with complete remission being achieving by 70% of disease-modifying antirheumatic drugs-refractory TAK patients at 6 months

Efficacy and safety of TNF-\u3b1 antagonists and tocilizumab in Takayasu arteritis: Multicenter retrospective study of 209 patients

To assess safety and efficacy of TNF-\u3b1 antagonists and tocilizumab in patients with Takayasu arteritis (TAK)