A Randomized, Placebo-Controlled Phase III Extension Trial of the Long-Term Safety and Tolerability of Anifrolumab in Active Systemic Lupus Erythematosus.

OBJECTIVE: To explore long-term safety and tolerability of anifrolumab 300 mg compared with placebo in patients with systemic lupus erythematosus (SLE) who completed a Treatment of Uncontrolled Lupus via the Interferon Pathway (TULIP) trial and enrolled in the placebo-controlled 3-year long-term extension (LTE) study (ClinicalTrials.gov identifier: NCT02794285). METHODS: In the blinded LTE study, patients continued anifrolumab 300 mg, switched from anifrolumab 150 mg to 300 mg, or were re-randomized from placebo to receive either anifrolumab 300 mg or to continue placebo, administered every 4 weeks. Primary comparisons in the LTE study were between patients who received anifrolumab 300 mg or placebo throughout the TULIP and LTE studies. For rare safety events, comparisons included patients who received any anifrolumab dose during TULIP or LTE. When exposure differed, exposure-adjusted incidence rates (EAIRs) per 100 patient-years were calculated. RESULTS: In the LTE study, EAIRs of serious adverse events (SAEs) were 8.5 with anifrolumab compared with 11.2 with placebo; likewise, EAIRs of AEs leading to treatment discontinuation were 2.5 versus 3.2, respectively. EAIRs of non-opportunistic serious infections were comparable between groups (3.7 with anifrolumab versus 3.6 with placebo). Exposure-adjusted event rates of COVID-related AEs, including asymptomatic infections, were 15.5 with anifrolumab compared with 9.8 with placebo. No COVID-related AEs occurred in fully vaccinated individuals. EAIRs of malignancy and major acute cardiovascular events were low and comparable between groups. Anifrolumab was associated with lower cumulative glucocorticoid use and greater mean improvement in the SLE Disease Activity Index 2000, compared with placebo. CONCLUSION: This LTE study represents the longest placebo-controlled clinical trial performed in SLE to date. No new safety findings were identified in the LTE study, supporting the favorable benefit-risk profile of anifrolumab for patients with moderate-to-severe SLE receiving standard therapy.

Symptom-based clusters of hospitalized patients with severe acute respiratory illness by SARS-CoV-2 in Brazil.

BACKGROUND: COVID-19 has shown a broad clinical spectrum, ranging from asymptomatic to mild, moderate, and severe infections. Many symptoms have already been identified as typical of COVID-19, but few studies show how they can be useful in identifying clusters of patients with different severity of illness. This interpretation may help to recognize the different profiles of symptoms of COVID-19 expressed in a population at certain time. The aim of this study was to identify symptom-based clusters of hospitalized patients with severe acute respiratory illness by SARS-CoV-2 in Brazil. The clusters were evaluated based on sociodemographic characteristics, admission to the Intensive Care Unit (ICU), use of respiratory support, and outcome. METHODS: The Multiple Correspondence Analysis (MCA)-based cluster analysis was applied to symptoms presented before admission. Pearson's chi-square test was used to compare the proportions of symptoms between the clusters and to examine differences in the calculated rates for the following variables: sex, age group, race, Brazilian region, use of respiratory support, admission to the ICU and outcome. RESULTS: Three COVID-19 clusters with distinct symptom profiles were identified by MCA-based cluster analysis. Cluster 1 had the mildest severity profile, with the lowest frequencies for most symptoms investigated. Cluster 2 had a severe respiratory profile, with the highest frequencies of patients with dyspnea, respiratory discomfort and O2 saturation< 95%. Cluster 2 was also the most prevalent in all Brazilian regions and had the highest percentages of patients who used invasive respiratory support (27.4%) (p-value<0.001), were admitted to the ICU (42.6%) (p -value<0.001) and died (39.0%) (p-value<0.001). Cluster 3 had a prominent profile of gastrointestinal symptoms. CONCLUSIONS: The study identified three distinct COVID-19 clusters based on the symptoms presented by patients with severe acute respiratory illness by SARS-CoV-2, but without distinction in their prevalence in the Brazilian regions.