Outcome of COVID-19 in patients with rheumatic and inflammatory diseases treated with mycophenolic acid: data from the French RMD COVID-19 cohort.

BACKGROUND: Patients with inflammatory rheumatic and musculoskeletal diseases (iRMD) receiving mycophenolic acid (MPA) may have a less favourable outcome from COVID-19 infection. Our aim was to investigate whether MPA treatment is associated with severe infection and/or death. METHODS: IRMD patients with and without MPA treatment with highly suspected/confirmed COVID-19 were included in this observational multicentre study. The primary outcome was death rate from COVID-19 with secondary objectives to determine the severity of infection and length of hospital stay. Outcome comparisons were made using regression models with and without adjustment on prespecified confounding factors. ORs, sub-HR (sHR) and 95% CIs were calculated using patients not treated with MPA as a reference group. RESULTS: Of the 1977 patients, 1928 were not treated with MPA (393 were MPA eligible), and 49 patients were treated with MPA. MPA-treated patients had more severe disease, longer hospital stays and higher death rate from COVID-19 than non-MPA patients (OR 8.02 (95% CI 3.35 to 19.20), p<0.001; sHR 0.57 (95% CI 0.33 to 0.98), p=0.040; OR 11.58 (95% CI 4.10 to 32.69), p<0.001). In adjusted analyses, however, no outcome was independently associated with MPA treatment. Death rate, severity and length of hospital stay of MPA-treated patients were not significantly different from those of not treated but MPA-eligible patients. CONCLUSION: MPA therapy is not associated with a more severe COVID-19 infection. However, due to increased vulnerability of developing a severe form of COVID-19, careful consideration should be taken with iRMD patients likely to be treated with MPA. TRIAL REGISTRATION NUMBER: NCT04353609.

COVID-19 infection among patients with autoinflammatory diseases: a study on 117 French patients compared with 1545 from the French RMD COVID-19 cohort: COVIMAI - the French cohort study of SARS-CoV-2 infection in patient with systemic autoinflammatory diseases.

OBJECTIVE: There is little known about SARS-CoV-2 infection in patients with systemic autoinflammatory disease (SAID). This study aimed to describe epidemiological features associated with severe disease form and death. Mortality between patients with and without SAID hospitalised for SARS-CoV-2 infection was compared. METHODS: A national multicentric prospective cohort study was conducted from the French Rheumatic and Musculoskeletal Diseases (RMD) COVID-19 cohort. Patients with SAID were matched with patients with non-SAID on age±7 years, gender and number of comorbidities to consider important confounding factors. Impact of SAID on severity of SARS-CoV-2 infection was analysed using multinomial logistic regression for severity in three classes (mild, moderate and severe with mild status as reference). Fine-Gray regression model for length of hospital stay and binomial logistic regression model for risk of death at 30 days. RESULTS: We identified 117 patients with SAID (sex ratio 0.84, 17 children) and compared them with 1545 patients with non-autoinflammatory immune-mediated inflammatory disorders (non-SAID). 67 patients had a monogenic SAID (64 with familial Mediterranean fever). Other SAIDs were Behçet' disease (n=21), undifferentiated SAID (n=16), adult-onset Still disease (n=9) and systemic-onset juvenile idiopathic arthritis (n=5). Ten adults developed severe form (8.6%). Six patients died. All children had a benign disease. After matching on age±7 years, sex and number of comorbidities, no significant difference between the two groups in length of stay and the severity of infection was noted. CONCLUSION: As identified in the whole French RMD COVID-19 cohort, patients with SAID on corticosteroids and with multiple comorbidities are prone to develop more severe COVID-19 forms.

Primary Thromboprophylaxis in Ambulatory Pancreatic Cancer Patients Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Patients with pancreatic cancer (PC) carry the highest risk of venous thromboembolism (VTE) amongst all cancer patients. Appropriate use of primary thromboprophylaxis might significantly and safely reduce its burden. We performed a systematic review of published studies and meeting abstracts using MEDLINE and EMBASE through July 2020 to evaluate the efficacy and safety of primary thromboprophylaxis in ambulatory PC patients receiving chemotherapy. The Mantel-Haenszel random effect model was used to estimate the pooled event-based risk ratio (RR) and the pooled absolute risk difference (RD) with a 95% confidence interval (CI). Five randomized controlled studies with 1003 PC patients were included in this meta-analysis. Compared to placebo, thromboprophylaxis significantly decreased the risk of VTE (pooled RR 0.31, 95% CI 0.19-0.51, p < 0.00001, I2 = 8%; absolute RD -0.08, 95% CI -0.12--0.05, p < 0.00001, I2 = 0%), with an estimated number needed to treat of 11.9 patients to prevent one VTE event. Similar reductions of VTE were observed in studies with parenteral (RR 0.30, 95% CI 0.17-0.53) versus oral anticoagulants (RR 0.37, 95% CI 0.14-0.99) and in studies using prophylactic doses of anticoagulants (RR 0.34, 95% CI 0.17-0.70) versus supra-prophylactic doses of anticoagulants (RR 0.27, 95% CI 0.08-0.90). The pooled RR for major bleeding was 1.08 (95% CI 0.47-2.52, p = 0.85, I2 = 0%) and the absolute RD was 0.00 (95% CI -0.02-0.03, p = 0.85, I2 = 0%). Evidence supports a net clinical benefit of thromboprophylaxis in ambulatory PC patients receiving chemotherapy. Adequately powered randomized phase III studies assessing the most effective anticoagulant and the optimal dose, schedule and duration of thromboprophylaxis to be used are warranted.

Low fetal hemoglobin percentage is associated with silent brain lesions in adults with homozygous sickle cell disease.

Silent white matter changes (WMCs) on brain imaging are common in individuals with sickle cell disease (SCD) and are associated with cognitive deficits in children. We investigated the factors predictive of WMCs in adults with homozygous SCD and no history of neurological conditions. Patients were recruited from a cohort of adults with homozygous SCD followed up at an adult sickle cell referral center for which steady-state measurements of biological parameters and magnetic resonance imaging scans of the brain were available. WMCs were rated by consensus, on a validated age-related WMC scale. The prevalence of WMCs was 49% (95% confidence interval [CI], 39%-60%) in the 83 patients without vasculopathy included. In univariable analysis, the patients who had WMCs were more likely to be older (P = .003) and to have hypertension (P = .02), a lower mean corpuscular volume (P = .005), a lower corpuscular hemoglobin concentration (P = .008), and a lower fetal hemoglobin percentage (%HbF) (P = .003). In multivariable analysis, only a lower %HbF remained associated with the presence of WMCs (odds ratio [OR] per 1% increase in %HbF, 0.84; 95% CI, 0.72-0.97; P = .021). %HbF was also associated with WMC burden (P for trend = .007). Multivariable ordinal logistic regression showed an inverse relationship between WMC burden (age-related WMC score divided into 4 strata) and HbF level (OR for 1% increase in %HbF, 0.89; 95% CI, 0.79-0.99; P = .039). Our study suggests that HbF may protect against silent WMCs, decreasing the likelihood of WMCs being present and their severity. It may therefore be beneficial to increase HbF levels in patients with WMCs.