Evolution of the use of corticosteroids for the treatment of hospitalised COVID-19 patients in Spain between March and November 2020: SEMI-COVID national registry

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID- 19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236- 996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%

Safety and tolerability of immune globulin intravenous in chronic inflammatory demyelinating polyradiculoneuropathy.

Abstract BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a common inflammatory neuropathy that can be progressive, stepwise progressive, or relapsing and remitting. OBJECTIVES: To further evaluate the long-term safety and tolerability of immune globulin intravenous, 10% caprylate-chromatography purified immune globulin intravenous in CIDP. DESIGN: Randomized multicenter trial. SETTING: Hospitals and outpatient clinics. Patients: Adults with CIDP (n = 117) [corrected]. INTERVENTIONS: Immune globulin intravenous, 10% caprylate-chromatography purified (2 g/kg of body weight) or placebo was infused as a baseline loading dose, followed by a maintenance dose (1 g/kg) every 3 weeks for up to 24 weeks. Patients who responded were rerandomized into a double-blind extension phase of immune globulin intravenous, 10% caprylate-chromatography purified (1 g/kg) or placebo every 3 weeks for up to 24 weeks. Patients who relapsed during the extension phase were withdrawn from the study. MAIN OUTCOME MEASURES: Additional analyses of safety and tolerability. RESULTS: Overall, 113 patients and 95 patients were exposed to immune globulin intravenous, 10% caprylate-chromatography purified and placebo, respectively. Exposure to immune globulin intravenous, 10% caprylate-chromatography purified was approximately twice that of placebo (1096 vs 575 infusions). Most maintenance dose courses were administered over 1 day in the immune globulin intravenous, 10% caprylate-chromatography purified (89.1% of 783 dose courses) and placebo (91.1% of 359 dose courses) groups. The most common drug-related adverse events (AEs) with immune globulin intravenous, 10% caprylate-chromatography purified were headache (4.0 per 100 infusions) and pyrexia (2.4 per 100 infusions). Five drug-related serious AEs (pulmonary embolism, pyrexia, vomiting, and 2 headache events) were reported in 3 patients (2.7%) exposed to immune globulin intravenous, 10% caprylate-chromatography purified. The incidence of drug-related serious AEs was higher after loading dose infusions than after maintenance dose infusions (4 AEs vs 1 AE). Age, weight, CIDP severity, and previous immune globulin intravenous exposure had no substantial effect on the percentage of patients with AEs, including serious AEs. CONCLUSION: Data support a favorable safety and tolerability profile for administration of immune globulin intravenous, 10% caprylate-chromatography purified as CIDP maintenance therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00220740

Electrophysiology in chronic inflammatory demyelinating polyneuropathy with IGIV.

Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) received immune globulin intravenous, 10% caprylate/chromatography purified (IGIV-C, Gamunex; n=59) or placebo (n=58) every 3 weeks for up to 24 weeks (first period) in a randomized, double-blind, parallel-group, response-conditional, crossover study. Motor and sensory nerves were assessed at baseline and endpoint/week 24. A nonsignificant trend toward improvement in the proximal amplitude of the most severely affected motor nerve was observed with IGIV-C (0.69+/-1.86 mV) versus placebo (0.47+/-2.29 mV), and a greater improvement of 1.08+/-2.15 mV with IGIV-C versus 0.46+/-2.03 mV with placebo (P=0.089) was observed with exclusion of data from Erb's point stimulation. Greater improvements from baseline favoring IGIV-C were observed for 127/142 electrophysiologic parameters. The averaged motor amplitudes from all motor nerves significantly improved with IGIV-C versus placebo [treatment difference, 0.62 mV; 95% confidence interval (CI), 0.05, 1.20; P=0.035], and conduction block decreased significantly (treatment difference, -5.54%; 95% CI, -10.43, -0.64; P=0.027), particularly in the lower limbs. Overall, the data suggest that IGIV-C improves electrophysiologic parameters in CIDP

Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes

Background Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure. Methods We undertook collaborative joint analysis of 13 HIV cohorts from Europe, North America, and Australia, involving patients who had had three-class virological failure (viral load &gt;1000 copies per mL for &gt;4 months). Regression analyses were used to quantify the associations between CD4-cell-count slope, HIV-1 RNA concentration, treatment information, and demographic characteristics. Predictors of death were analysed by Cox's proportional-hazards models. Findings 2488 patients were included. 2118 (85%) had started antiretroviral therapy with single or dual therapy. During 5015 person-years of follow-up, 276 patients died (mortality rate 5.5 per 100 person-years; 3-year mortality risk 15.3% (95% Cl 13.5-17.3). Risk of death was strongly influenced by the latest CD4-cell count with a relative hazard of 15.8 (95% CI 9.28-27.0) for counts below 50 cells per muL versus above 200 cells per muL. The latest viral load did not independently predict death. For any given viral load, patients on treatment had more favourable CD4-cell-count slopes than those off treatment. For patients on treatment and with stable viral load, CD4-cell counts tended to be increasing at times when the current viral load was below 10 000 copies per mL or 1.5 log(10) copies per mL below off-treatment values. Interpretation In patients for whom viral-load suppression to below the level of detection is not possible, achievement and maintenance of a CD4-cell count above 200 per muL becomes the primary aim. Treatment regimens that maintain the viral load below 10 000 copies per mL or at least provide 1.5 log(10) copies per mL suppression below the off-treatment value do not seem to be associated with appreciable CD4-cell-count decline

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis

.AbstractBackgroundInterferon beta is used to modify the course of relapsing multiple sclerosis. Despiteinterferon beta therapy, many patients have relapses. Natalizumab, an α4 integrinantagonist, appeared to be safe and effective alone and when added to interferonbeta-1a in preliminary studies.MethodsWe randomly assigned 1171 patients who, despite interferon beta-1a therapy, hadhad at least one relapse during the 12-month period before randomization to receivecontinued interferon beta-1a in combination with 300 mg of natalizumab (589patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks.The primary end points were the rate of clinical relapse at 1 year and the cumulativeprobability of disability progression sustained for 12 weeks, as measured by theExpanded Disability Status Scale, at 2 years.ResultsCombination therapy resulted in a 24 percent reduction in the relative risk of sustaineddisability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61to 0.96; P = 0.02). Kaplan–Meier estimates of the cumulative probability of progressionat two years were 23 percent with combination therapy and 29 percent withinterferon beta-1a alone. Combination therapy was associated with a lower annualizedrate of relapse over a two-year period than was interferon beta-1a alone (0.34vs. 0.75, P&lt;0.001) and with fewer new or enlarging lesions on T2-weighted magneticresonance imaging (0.9 vs. 5.4, P&lt;0.001). Adverse events associated with combinationtherapy were anxiety, pharyngitis, sinus congestion, and peripheral edema.Two cases of progressive multifocal leukoencephalopathy, one of which was fatal,were diagnosed in natalizumab-treated patients.ConclusionsNatalizumab added to interferon beta-1a was significantly more effective than interferonbeta-1a alone in patients with relapsing multiple sclerosis. Additional researchis needed to elucidate the benefits and risks of this combination treatment.(ClinicalTrials.gov number, NCT00030966.