Khanna D, Spino C, Johnson S, et al. - In patients with diffuse cutaneous systemic sclerosis (dcSSc), researchers tested the effectiveness and safety of abatacept, a CTLA4 immunoglobulin fusion protein. For this 12-month, randomized, double-blind, placebo-controlled trial, 88 candidates were randomized 1:1 to receive either subcutaneous abatacept 125 mg or matching placebo, stratified by duration of dcSSc. At 12 months, the adjusted mean change in modified Rodnan skin score (MRSS) was -6.24 and -4.49 units in the abatacept and in the placebo, respectively, with an adjusted mean treatment difference of -1.75 units. In the placebo group, the proportion of individuals needing escape therapy was higher relative to the abatacept group. The decline in the MRSS over 12 months was clinically and significantly greater in the abatacept group vs the placebo group in the inflammatory and normal-like skin gene expression subsets. Overall, the authors concluded that abatacept was well-tolerated, but there was no statistically significant change in the MRSS. In support of abatacept, secondary outcome measures, including gene expression subsets, demonstrated evidence. In a Phase III trial, these results should be verified.