Defining the course of neurosarcoidosis according to presentation at onset and disease modifying treatment: a cohort study of 84 patients

Background: Neurosarcoidosis is a rare manifestation of sarcoidosis with heterogeneous presentations. Patient management is challenging due to the current lack of knowledge about the long-term disease course. Objective: To identify specific disease courses of neurosarcoidosis according to the clinical and paraclinical presentations at onset. Methods: We conducted an observational multicenter cohort study by retrospectively collecting data from the medical records of 84 patients diagnosed with definite, probable, or possible neurosarcoidosis in three tertiary referral centers in France (Nancy, Strasbourg, and Bordeaux). We collected demographic characteristics, clinical and paraclinical data at the beginning of patient management, and during follow-up under the different treatment lines. Two expert neurologists determined disease course profiles. Results: The mean follow-up was 6.6 years. Almost every patient (96.4%) received steroids at some point of their follow-up. Tumor Necrosis Factor-alpha blockers were given in 10.7% as first-line treatment and in 33.3% during follow-up. Every patient presented with a relapsing disease, often monophasic (75%) and sometimes polyphasic with the recurrence of identical manifestations (11.9%). Patients developing new neurological symptoms during follow-up were a minority (13.1%). No patients exhibited a progressive course. Patients with isolated cranial nerves injury or aseptic meningitis always exhibited a monophasic course, and 62.5–75% of them had a full recovery after first-line treatments. This proportion was 15.6% in other forms of the disease. Those with peripheral presentations were more likely to present a polyphasic course than patients with other forms of neurosarcoidosis. Spinal cord presentations were monophasic, but resulted in sequelae and exhibited poor response to first-line treatments despite frequent use of TNF-alpha blockers. Conclusion: Identification of these disease course profiles, based on the initial clinical and paraclinical presentation, could guide the clinician to select the optimal therapeutic approach and follow-up modalities for their patients with neurosarcoidosis

Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia

International audienceImportance 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 unit, TCZ did not reduce WHO-CPS scores lower than 5 at day 4 but might have reduced the risk of NIV, MV, or death by day 14. No difference on day 28 mortality was found. Further studies are necessary for confirming these preliminary results.Trial Registration ClinicalTrials.gov Identifier: NCT0433180

Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

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Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial

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