Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): a double-blind, double-dummy, randomised, controlled, phase 2b trial

作者：Toby M. Maher, Veronica A Tudor, Peter Saunders, Michael Gibbons, Sophie Fletcher, Christopher P. Denton, Rachel K. Hoyles, Helen Parfrey, Elisabetta Renzoni, Maria Kokosi, Athol U. Wells, Deborah Ashby, Mátyás Szigeti, Philip L. Molyneaux, Mohammed Akil, Daphne Babalis, Nazia Chaudhuri, Felix Chua, Arnab Data, Dhananjay Desai, Shrish Dubey, Natalie Dwyer, Marcus Flather, Richard Fordham, Carlota Grossi Sampedro, Frances Hall, Ira Jakupovic, Gregory J. Keir, Bipen D. Patel, Henry Penn, Arvind Rajasekaran, Lisa Spencer, Vicky Tsipouri, Zhe Wu, Georgio Xydopoulos, Fernando Zanghelini · 发表于：The Lancet Respiratory Medicine · 年份：2022 · DOI：10.1016/s2213-2600(22)00359-9 · 被引用次数：281 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Inflammatory Myopathies and Dermatomyositis、Systemic Sclerosis and Related Diseases

Background Rituximab is often used as rescue therapy in interstitial lung disease (ILD) associated with connective tissue disease (CTD), but has not been studied in clinical trials. This study aimed to assess whether rituximab is superior to cyclophosphamide as a treatment for severe or progressive CTD associated ILD. Methods We conducted a randomised, double-blind, double-dummy, phase 2b trial to assess the superiority of rituximab compared with cyclophosphamide. Patients aged 18–80 years with severe or progressive ILD related to scleroderma, idiopathic inflammatory myositis, or mixed CTD, recruited across 11 specialist ILD or rheumatology centres in the UK, were randomly assigned (1:1) to receive rituximab (1000 mg at weeks 0 and 2 intravenously) or cyclophosphamide (600 mg/m 2 body surface area every 4 weeks intravenously for six doses). The primary endpoint was rate of change in forced vital capacity (FVC) at 24 weeks compared with baseline, analysed using a mixed-effects model with random intercepts, adjusted for baseline FVC and CTD type. Prespecified secondary endpoints reported in this Article were change in FVC at 48 weeks versus baseline; changes from baseline in 6 min walk distance, diffusing capacity of the lung for carbon monoxide (DL CO ), physician-assessed global disease activity (GDA) score, and quality-of-life scores on the St George's Respiratory Questionnaire (SGRQ), King's Brief Interstitial Lung Disease (KBILD) questionnaire, and European Quality of Life...