In patients with early diffuse cutaneous systemic sclerosis (dcSSc), treatment with abatacept may be safe and promote overall global improvement, according to study results published in Lancet Rheumatology.
Researchers conducted a 6-month, open-label extension of a 12-month, phase 2, double-blind, randomized trial — A Study of Subcutaneous Abatacept to Treat Diffuse Cutaneous Systemic Sclerosis (ASSET; ClinicalTrials.gov Identifier: NCT02161406) — at 22 sites in the United States, the United Kingdom, and Canada. They sought to evaluate the safety and efficacy of abatacept on the skin, joints, and disability in patients with dcSSc.
All study participants were aged at least 18 years and had dcSSc for less than 3 years from the time of their first non-Raynaud symptom. Participants received 12 months of treatment with abatacept or placebo in the double-blind phase, followed by an open-label extension period in which an additional 6 months of abatacept 125 mg was administered subcutaneously every week. The primary endpoint of the double-blind trial was modified Rodnan Skin Score (mRSS) at 12 months, which was re-evaluated in the open-label extension at 18 months.
Between September 22, 2014, and March 15, 2017, a total of 88 participants were randomly assigned in the double-blind trial to either abatacept (n=44) or placebo (n=44). Overall, 32 participants from each treatment group completed the 6-month, open-label extension.
In patients who received abatacept, the researchers observed a mean improvement from baseline in mRSS at 12 months (-6.6±6.4), with further improvement during the open-label extension phase at 18 months (-9.8±8.1). Participants in the placebo group had a mean improvement from baseline in mRSS at 12 months (-3.7±7.6), with further improvement at 18 months (-6.3±9.3).
During the open-label period, infections were reported in 9 patients in the placebo-abatacept group (12 adverse events and 1 serious adverse event) and in 11 patients in the abatacept-abatacept group (14 adverse events and 1 serious adverse event). During the 12-month double-blind phase, 2 deaths occurred in the abatacept group, which were associated with the development of scleroderma renal crisis; however, no deaths were reported during the open-label extension.
Study limitations included the possibility of survivor bias, missing data, and the small sample size.
Researchers concluded that the findings from the study warrant further assessment in a phase 3, randomized trial before any definitive conclusions can be drawn about the risks and benefits associated with the use of abatacept in patients with dcSSc.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Chung L, Spino C, McLain R, et al. Safety and efficacy of abatacept in early diffuse cutaneous systemic sclerosis (ASSET): open-label extension of a phase 2, double-blind randomised trial. Lancet Rheumatol. Published online October 19, 2020. doi:10.1016/S2665-9913(20)30237-X