Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals

Social protection as development policy. A new international agenda for action.

At the turn of the millennium, social protection became a new priority for both states of the global South and international development policy more generally. As, in the past, social protection policies were considered unsuitable for development countries, the elevation of social protection to the level of a preferred instrument of development marks a fundamental paradigm shift. This shift began in the late 1990s, driven by disenchantment with the results of economic adjustment programmes, the 1997 Asian economic crisis, and a heightened awareness of the negative effects of global poverty. Social protection thus became a preferred instrument of the Millennium Development Goals, while the World Bank promoted social protection as a key component of international poverty reduction strategies (social risk management). The Department for International Development (DfID) in the United Kingdom, along with other organisations, promoted a development model centred on the rights of the poor. Successful social protection programmes developed in the Global South – such as Brazilian and South African social pension schemes and conditional cash transfers (CCT) established in Mexico and Brazil – were adopted as model programmes at the global level. The purpose of this article is to analyse the emergence of social protection in development policies. From this perspective, it examines the various types of programmes promoted by the international community, with a specific focus on CCT. It concludes with an assessment of the relative appropriateness of social protection policies for developing countries

ON RELATIONSHIPS BETWEEN INTEGRATED POLICIES FOR SUSTAINABLE URBAN DEVELOPMENT AND URBAN GOVERNANCE

The aim of this paper is not to open a debate on the various meanings of governance and urban governance, nor to discuss in depth the relevance of integrated urban policy strategies. Its starting point is to explain why these 'new urban policies' are placed on political agendas and how they contribute to the transformation of the urban government system and to the implementation of urban governance. This paper has arisen from two basic questions. The first question concerns the variety of definitions of these concepts and the ways in which they well up in the context of elaborating and implementing public policy. The second question looks specifically at the relationships holding between integrated policies of urban development and systems of urban regulation and governance. It seeks to render explicit the construction of urban governance by analysing the process of co-operation among the various agents at work in the city. Copyright (c) 2005 by the Royal Dutch Geographical Society KNAG.

The reframing of family policies in France: processes and actors

French family policy is generally considered as one of the oldest, most explicit and extensive in Europe. To understand the changes in this public policy sector during the past decades, we first discuss the roots and scope of family policy and then propose a 'process tracing' to identify sequences, based on two sets of opposing principles that have shaped French family policy history: universality versus selectivity and French 'familialisme' versus individualism. In the last two sections, a detailed analysis of the dynamics of change is presented before focusing on the role of the different protagonists of this change: political actors, high-ranking civil servants, family associations and experts. We underline the importance of a small group of high-ranking civil servants, called the 'welfare elite', in this specific sector, whose contribution explains the permanent French specificity and path dependency