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Abatacept in Early Diffuse Cutaneous Systemic Sclerosis - Results of a Phase 2 Investigator-Initiated, Multicenter, Double-Blind Randomized Placebo-Controlled Trial

Title: Abatacept in Early Diffuse Cutaneous Systemic Sclerosis - Results of a Phase 2 Investigator-Initiated, Multicenter, Double-Blind Randomized Placebo-Controlled Trial
Authors: Khanna, D; Spino, C; Johnson, S; Chung, L; Whitfield, M; Denton, CP; Berrocal, V; Franks, J; Mehta, B; Molitor, J; Steen, VD; Lafyatis, R; Simms, RW; Gill, A; Kafaja, S; Frech, TM; Hsu, V; Domsic, RT; Pope, JE; Gordon, JK; Mayes, MD; Schiopu, E; Young, A; Sandorfi, N; Park, J; Hant, FN; Bernstein, EJ; Chatterjee, S; Castelino, FV; Ajam, A; Wang, Y; Wood, T; Allanore, Y; Matucci-Cerinic, M; Distler, O; Singer, O; Bush, E; Fox, D; Furst, DE
Source: Arthritis and Rheumatology , 72 (1) pp. 125-136. (2020)
Publication Year: 2020
Collection: University College London: UCL Discovery
Description: OBJECTIVES: T cells play a key role in the pathogenesis of early systemic sclerosis. This study assessed the safety and efficacy of abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc). // METHODS: A 12-month, randomized, double-blind, placebo-controlled trial with participants randomized in a 1:1 ratio to either abatacept 125 mg subcutaneous or matching placebo, stratified by duration of dcSSc. Escape therapy was allowed at six months for worsening disease. The co-primary end points were change in modified Rodnan skin score (mRSS) and safety over 12 months. Treatment differences in longitudinal outcomes were assessed using linear mixed models, with outcomes censored after initiation of escape therapy. Baseline skin tissue was classified into intrinsic gene expression subsets. // RESULTS: Among 88 participants, the adjusted mean change in mRSS at 12 months was -6.24 units in the abatacept and -4.49 units in the placebo, with adjusted mean treatment difference of -1.75 units (p=0.28). Two secondary outcome measures (HAQ-DI and a composite measure) were clinically and statistically significant favoring abatacept. A larger proportion of placebo subjects required escape therapy relative to abatacept (36% vs. 16%). Decline in mRSS over 12 months was clinically and significantly higher in abatacept vs. placebo for the Inflammatory (p
Document Type: article in journal/newspaper
File Description: text
Language: English
Relation: https://discovery.ucl.ac.uk/id/eprint/10078921/1/Khanna%20ASSET%20accepted%20UCL%20version.pdf; https://discovery.ucl.ac.uk/id/eprint/10078921/
Availability: https://discovery.ucl.ac.uk/id/eprint/10078921/1/Khanna%20ASSET%20accepted%20UCL%20version.pdf; https://discovery.ucl.ac.uk/id/eprint/10078921/
Rights: open
Accession Number: edsbas.63A92ACF
Database: BASE