Safety and efficacy of abatacept in early diffuse cutaneous systemic sclerosis (ASSET): open-label extension of a phase 2, double-blind randomised trial

Abstract

BackgroundWe recently reported that abatacept was well tolerated with potential efficacy for early diffuse cutaneous systemic sclerosis (dcSSc) in a phase II placebo-controlled randomized trial. We report here the results of the six-month open-label extension (OLE) period. MethodsThis was a double-blind, randomized controlled trial with OLE conducted at 22 centers in the US, Canada, and the UK (clinicaltrials.gov NCT 02161406). Participants with dcSSc of < 3 years duration from first non-Raynaud symptom were treated for six months with subcutaneous abatacept 125 mg weekly after completion of 12 months of abatacept or placebo during the double-blind period. Safety and exploratory efficacy endpoints, including modified Rodnan skin score (mRSS), were assessed over the 18-month period. Descriptive statistics were performed including all participants who completed the double-blind period and received at least one dose of open-label treatment. FindingsEighty-eight participants were randomized in the double-blind period between September 22, 2014 and March 15, 2017, and 32 in each group completed the six-month OLE. Infections occurred in nine (12 events, one serious) and 11 (14 events, one serious) participants in the placebo-abatacept and abatacept-abatacept groups, respectively. There were no deaths during the OLE. Abatacept resulted in a mean(SD) improvement in mRSS of -6•6(6•43) at month 12, with further improvement in the open-label period, resulting in a mean(SD) improvement of -9•8(8•14) from baseline to month 18. Participants who initially received placebo experienced a Implications of all the available evidenceGiven the lack of disease-modifying treatment options for patients with early systemic sclerosis, combined with the morbidity and mortality associated with this disease, data from our trial provide hope for a potential future treatment. These data should be further investigated in an adequate, randomized, well-controlled, phase 3 trial before definitive conclusions can

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