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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


Abstract

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<0.001) and Normal-like skin gene expression subsets (p=0.03). 35 participants in the abatacept versus 40 in the placebo had adverse events (AEs), including two and one deaths, respectively.
CONCLUSIONS
In this Phase 2 trial, abatacept was well tolerated, but change in mRSS was not statistically significant. Secondary outcome measures, including gene expression subsets, showed some evidence in favor of abatacept. These data should be confirmed in a Phase 3 trial. This article is protected by copyright. All rights reserved.

Abstract

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<0.001) and Normal-like skin gene expression subsets (p=0.03). 35 participants in the abatacept versus 40 in the placebo had adverse events (AEs), including two and one deaths, respectively.
CONCLUSIONS
In this Phase 2 trial, abatacept was well tolerated, but change in mRSS was not statistically significant. Secondary outcome measures, including gene expression subsets, showed some evidence in favor of abatacept. These data should be confirmed in a Phase 3 trial. This article is protected by copyright. All rights reserved.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
Dewey Decimal Classification:610 Medicine & health
Date:1 January 2020
Deposited On:16 Aug 2019 08:13
Last Modified:29 Dec 2019 02:02
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:2326-5191
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/art.41055
PubMed ID:31342624

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