Trump’s election foreshadows further divisions in Europe. CEPS Commentary, 9 November 2016

The victory of Donald Trump has sent shockwaves throughout Europe. Under President Trump, US domestic and foreign policies can be expected to become more volatile and less predictable. For years, Trump has fairly consistently espoused the view that the US has been taken advantage of by the free-riding of its so-called ‘strategic’ partners. With Trump, a US retreat from the world can be expected. Guarantees that have underpinned more than 70 years of post-war global order are melting into air. This will affect Europe, in particular in the fields of trade and security and call into question previously shared values

A Commission of concrete steps rather than grand strategy. Policy Priorities for 2019-2024, 19 September 2019

The von der Leyen Commission inherits a Union that has largely overcome its ‘polycrises’. The economy has stabilised and employment continues to grow, despite the slowdown in the global economy. Apart from some fluctuations in the risk premium on Italian government bonds, the financial markets are largely without tension. The flow of refugees has fallen to a fraction of the peak registered three and four years ago. At the same time, trust in the EU and its institutions has increased steadily across most member states, reaching near-record values, and participation rates in the recent elections for the European Parliament also increased considerably. Against this background, it is not surprising that the various Eurosceptic parties did not do as well as expected in these elections. In the absence of unforeseen major shocks, the EU institutions should now be less engaged in crisis management and more able to pursue a long-term strategic agenda. The President-elect of the European Commission has also set out her overall programme, which is highly ambitious in many respects, hits all the right notes in terms of policy prioritisation but, significantly, does not recognise any trade-offs between different goals. Recognising trade-offs is essential for policymaking. For example, protecting citizens from terrorist threats might necessitate limitations to their freedoms. Fostering a climate-neutral Europe has costs that might weigh on growth and be difficult to distribute fairly. Any concrete political strategy will need to address these trade-offs – which political leaders typically fail to do

The EU’s Response to the Refugee Crisis: Taking Stock and Setting Policy Priorities. CEPS Essay No. 20, 16 December 2015

What have been the most important EU policy and legal responses to the 2015 refugee crisis? Is Europe taking effectively responsibility in compliance with its founding principles? This Essay takes stock of the main results and policy outputs from the EU’s interventions in the refugee crisis. It critically highlights the outstanding policy dilemmas confronting the adopted instruments and puts forwards a set of policy priorities to guide the next phases of the European Agenda on Migration

The European Border and Coast Guard Addressing migration and asylum challenges in the Mediterranean? CEPS Task Force Report, 1 February 2017

The humanitarian refugee crisis in Europe of 2015-2016 has revealed several unfinished elements and shortcomings in current EU policies and approaches to migration, asylum and borders, particularly those applying in southern EU maritime borders and frontier states in the Mediterranean. This book provides a critical examination of the main issues and lessons learned from this crisis and gives an up-to-date assessment of the main policy, legal and institutional responses that have been put in place at the EU level. It further examines the extent to which these responses can be expected to work under the current system of sharing responsibilities among EU member states in assessing asylum applications and ensuring a consistent implementation of EU legal standards that comply with the rule of law and fundamental rights. This report is based on original research and draws upon the existing literature, along with the discussions of a CEPS Task Force that met over six months, under the chairmanship of Enrico Letta, President of the Jacques Delors Institute, Dean of the Paris School of International Affairs (PSIA) at Sciences Po and former Prime Minister of Italy. The rapporteurs offer specific recommendations and possible scenarios for policy optimisation and assess the extent to which the establishment of a European Border and Asylum Service (EBAS) could address the current gaps and challenges in EU and member states’ migration policies

Long-term effect of tocilizumab in patients with giant cell arteritis:open-label extension phase of the Giant Cell Arteritis Actemra (GiACTA) trial

Background: The combination of tocilizumab plus a glucocorticoid taper is effective in maintaining clinical remission without requiring additional glucocorticoid therapy in patients with giant cell arteritis, as shown in part one of the Giant Cell Arteritis Actemra (GiACTA) trial. However, the duration of the tocilizumab effect after discontinuation is unknown. Here, we explored the maintenance of efficacy 1 year after discontinuation of tocilizumab treatment, the effectiveness of retreatment with tocilizumab after relapse, and the long-term glucocorticoid-sparing effect of tocilizumab. Methods: In part one of the GiACTA trial, 251 patients were randomly assigned (2:1:1:1) to receive subcutaneous tocilizumab (162 mg) once a week or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks. Patients in clinical remission stopped masked injections at 1 year (the conclusion of part one). In part two, treatment was at the investigators' discretion and could consist of no treatment, tocilizumab, glucocorticoids, methotrexate, or combinations of these, for two years. Maintenance of efficacy as assessed by clinical remission (defined as absence of relapse determined by the investigator), cumulative glucocorticoid dose, and long-term safety were exploratory objectives in part two of the trial. This trial is registered at ClinicalTrials.gov, NCT01791153. Findings: 215 patients participated in part two of the trial; 81 patients who were randomly assigned to tocilizumab once a week in part one were in clinical remission after 1 year, of whom 59 started part two on no treatment. 25 of these 59 patients (42%) maintained tocilizumab-free and glucocorticoid-free clinical remission throughout part two. Median (95% CI) cumulative glucocorticoid doses over 3 years were 2647 mg (1987\u20133507) for tocilizumab once a week, 3948 mg (2352\u20135186) for tocilizumab-every-other-week, 5277 mg (3944\u20136685) for placebo with a 26-week prednisone taper, and 5323 mg (3900\u20136951) for placebo with a 52-week prednisone taper (van Elteren p 640\ub7001, tocilizumab once a week vs placebo groups; p<0\ub705, tocilizumab-every-other-week vs placebo groups). Tocilizumab-based regimens restored clinical remission among patients who experienced relapse in part two and were treated (median time to remission: 15 days for tocilizumab alone [n=17]; 16 days for tocilizumab plus glucocorticoids [n=36]; and 54 days for glucocorticoids alone [n=27]). No new or unexpected safety findings were reported over the full 3 years of the study. Interpretation: Giant cell arteritis remains a chronic disease that entails ongoing management and careful vigilance for disease relapse, but continuous indefinite treatment with immunosuppressive drugs is not required for all patients. A substantial proportion of patients treated with tocilizumab for one year maintain drug-free remission during the two years after tocilizumab cessation. For patients who experience relapse, tocilizumab can be used to manage relapses, but it remains prudent to include prednisone for patients who experience relapse because of the risk for vision loss. Funding: F Hoffmann-La Roche

New-onset versus relapsing giant cell arteritis treated with tocilizumab:3-year results from a randomized controlled trial and extension

OBJECTIVE: Tocilizumab plus prednisone induces sustained glucocorticoid-free remission in patients with giant cell arteritis (GCA). However, its long-term benefits in new-onset vs relapsing disease are uncertain and the value of weekly vs every-other-week dosing has not been evaluated. METHODS: In GiACTA part 1, patients with new-onset or relapsing GCA received blinded tocilizumab weekly (TCZ QW), tocilizumab every-other-week (TCZ Q2W), or placebo for 52 weeks with a prednisone taper. In part 2 (open-label), patients were treated at investigator discretion for 104 weeks. In this analysis, patients were evaluated according to their original treatment assignments and outcomes beyond 52 weeks were assessed. Outcomes of interest included time to first flare and cumulative glucocorticoid exposure over 3 years according to baseline disease status. RESULTS: Part 1 enrolled 250 patients; 215 entered part 2. At baseline, 48% had new-onset disease and 52% had relapsing disease. In patients with new-onset and relapsing disease, median time to first flare in the TCZ QW group was 577 and 575 days, respectively, vs 479 and 428 days with TCZ Q2W and 179 and 224 days with placebo; median cumulative glucocorticoid dose was 3068 mg and 2191 mg with TCZ QW, 4080 mg and 2353 mg with TCZ Q2W, and 4639 mg and 6178 mg with placebo. CONCLUSIONS: TCZ QW delays the time to flare and reduces cumulative glucocorticoid dose in patients with relapsing GCA and new-onset GCA. These data support initiating TCZ QW as part of first-line therapy in all patients with active GCA. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT01791153

Clinical and serological evaluation of a novel CENP-A peptide based ELISA

ABSTRACT: INTRODUCTION: Anti-centromere antibodies (ACA) are useful biomarkers in the diagnosis of systemic sclerosis (SSc). ACA are found in 20-40% of SSc patients and, albeit with lower prevalence, in patients with other systemic autoimmune rheumatic diseases. Historically, ACA were detected by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed by immunoassays using recombinant CENP-B. The objective of this study was to evaluate a novel CENP-A peptide ELISA. METHODS: Sera collected from SSc patients (n=334) and various other diseases (n=619) and from healthy controls (n=175) were tested for anti-CENP-A antibodies by the novel CENP-A enzyme linked immunosorbent assay (ELISA). Furthermore, ACA were determined in the disease cohorts by IIF (ImmunoConcepts), CENP-B ELISA (Dr. Fooke), EliA(R) CENP (Phadia) and line-immunoassay (LIA, Mikrogen). Serological and clinical associations of anti-CENP-A with other autoantibodies were conducted in one participating centre. Inhibition experiments with either the CENP-A peptide or recombinant CENP-B were carried out to analyse the specificity of anti-CENP-A and -B antibodies. RESULTS: The CENP-A ELISA results were in good agreement with other ACA detection methods. According to the kappa method, the qualitative agreements were: 0.73 (vs. IIF), 0.81 (vs. LIA), 0.86 (vs. CENP-B ELISA) and 0.97 (vs. EliA(R) CENP). The quantitative comparison between CENP-A and CENP-B ELISA using 265 samples revealed a correlation value of rho=0.5 (by Spearman equation). The receiver operating characteristic analysis indicated that the discrimination between SSc patients (n=131) and various controls (n=134) was significantly better using the CENP-A as compared to CENP-B ELISA (p<0.0001). Modified Rodnan skin score was significantly lower in the CENP-A negative group compared to the positive patients (p=0.013). Inhibition experiments revealed no significant cross reactivity of anti-CENP-A and anti-CENP-B antibodies. Statistically relevant differences for gender ratio (p=0.0103), specific joint involvement (Jaccoud) (p=0.0006) and anti-phospholipid syndrome (p=0.0157) between ACA positive SLE patients and the entire SLE cohort were observed. CONCLUSION: Anti-CENP-A antibodies as determined by peptide ELISA represent a sensitive, specific and independent marker for the detection of ACA and are useful biomarkers for the diagnosis of SSc. Our data suggest that anti-CENP-A antibodies are a more specific biomarker for SSc than antibodies to CENP-B. Furthers studies are required to verify these findings.status: publishe

Priorities for the Juncker Commission: Policy recommendations and advice from the research team at CEPS. CEPS Special Report No. 92, 22 October 2014

In the months leading up to his nomination as President of the European Commission by the European Council in June 2014 through to his approval by the European Parliament in mid-July and finally his approval at a second special summit in August, CEPS’ researchers have closely followed the travails of Jean-Claude Juncker. We have also carefully studied his fundamental restructuring of the College in re-grouping commissioners around seven project teams, each headed by a vice-president. In our view, these changes promise to improve internal coordination, policy-making and transparency of rule-making and hopefully will reduce the personalisation of portfolios. This Special Report brings together under a single cover a series of 14 separate commentaries prepared by senior CEPS researchers, offering their assessment of these profound changes underway and their policy advice to the new commissioners from the perspective of their field of specialisation

Deliberative Democracy in the EU. Countering Populism with Participation and Debate. CEPS Paperback

Elections are the preferred way to freely transfer power from one term to the next and from one political party or coalition to another. They are an essential element of democracy. But if the process of power transfer is corrupted, democracy risks collapse. Reliance on voters, civil society organisations and neutral observers to fully exercise their freedoms as laid down in international human rights conventions is an integral part of holding democratic elections. Without free, fair and regular elections, liberal democracy is inconceivable. Elections are no guarantee that democracy will take root and hold, however. If the history of political participation in Europe over the past 800 years is anything to go by, successful attempts at gaining voice have been patchy, while leaders’ attempts to silence these voices and consolidate their own power have been almost constant (Blockmans, 2020). Recent developments in certain EU member states have again shown us that democratically elected leaders will try and use majoritarian rule to curb freedoms, overstep the constitutional limits of their powers, protect the interests of their cronies and recycle themselves through seemingly free and fair elections. In their recent book How Democracies Die, two Harvard professors of politics write: “Since the end of the Cold War, most democratic breakdowns have been caused not by generals and soldiers but by elected governments themselves” (Levitsky and Ziblatt, 2018)