A peripheral blood type I interferon (IFN) gene signature can be found in approximately 50% of patients with rheumatoid arthritis (RA),1 suggesting that activation of the type I IFN system contributes to RA pathogenesis within this subset of patients. Therefore, the question arises whether blocking the type I IFN response, especially in patients with a high type I IFN gene signature, would be an effective treatment approach for RA. To address this question and to estimate the potential for the future planning of a larger study, we conducted a randomised, double-blind, placebo-controlled multicentre pilot trial, in which we planned to include 24 patients with RA with active disease and a high type I IFN gene signature to receive the type I IFN receptor blocking antibody anifrolumab2 or placebo intravenously every 4 weeks for a total of six doses (trial registration number NCT03435601; start of study: December 2017; end of study: November 2020). Inclusion criteria, among others, were current treatment with a conventional synthetic disease-modifying antirheumatic drug (DMARD) and failure to clinically respond to at least one Tumor necrosis factor alpha (TNF)-inhibitor but no more than a total of three biological DMARDs; patients had to have moderately to highly active disease. To identify patients with RA with a high IFN signature, we applied a four-gene (IFI27, IFI44, IFI44L, RSAD2) quantitative PCR-based test (QIAGEN) using RNA extracted from whole blood collected in PAXgene Blood RNA tubes (PreAnalytiX).3 Recruitment turned out difficult not least because of the evolution of the COVID-19 pandemic and, therefore, the study was prematurely stopped. Here, we report on the overall results of this pilot trial.