medwireNews: Findings from the phase II ASSET trial suggest that patients with diffuse cutaneous systemic sclerosis (dcSSc) who are treated with abatacept do not experience significantly greater improvements in skin disease than those given placebo.
However, the investigators say that the drug was well tolerated, and participants in the abatacept arm fared better in some secondary outcome measures than those in the placebo group.
As reported in Arthritis & Rheumatology, the adjusted least-squares (LS) mean improvement in modified Rodnan skin score (mRSS) from baseline to the 1-year follow-up was 6.24 points for the 44 patients randomly assigned to receive subcutaneous abatacept 125 mg/week, compared with 4.49 points for the 44 participants given placebo, giving a nonsignificant between-group difference of 1.75 points for the primary efficacy outcome.
On the other hand, Dinesh Khanna (University of Michigan, Ann Arbor, USA) and colleagues found “statistically significant and clinically meaningful treatment differences” in physical function between the two groups.
Indeed, LS mean HAQ-DI scores improved by 0.17 points over 1 year in the abatacept group but worsened by 0.11 points in the placebo group, giving a significant difference of 0.28 points between the arms.
Participants given abatacept also experienced a significantly greater average improvement in ACR-CRISS score – a composite endpoint including cardio-pulmonary-renal involvement and change in mRSS, HAQ-DI, forced vital capacity, and physician and patient global assessments – over the study period than those in the placebo group, at 0.68 versus 0.01 points.
The researchers conducted an exploratory subgroup analysis based on gene expression in skin biopsies, finding that the LS mean improvement in mRSS over 1 year was significantly greater with abatacept versus placebo for patients in the inflammatory and normal-like subgroups but not for those in the fibroproliferative group.
“These data are consistent with results from the pilot study of abatacept and extend these findings, for the first time, to a large placebo-controlled trial that shows intrinsic skin gene expression subsets may predict differential response to a targeted biological therapy,” write Khanna et al.
In all, 80% of patients in the abatacept and 91% of those given placebo experienced adverse events (AEs) over the study period, with 20% and 27%, experiencing serious AEs, respectively, and 5% in each group experiencing infectious AEs.
Two deaths in the abatacept arm and one in the placebo arm occurred during the trial. One person in the abatacept group died due to respiratory failure considered to be related to the study drug, following renal crisis not considered related to the study drug. The other two deaths were not judged to be related to the study drugs.
The ASSET investigators say that overall, “abatacept was well tolerated,” with “no new safety signals” emerging from the trial.
They conclude: “A Phase 3 trial should be conducted before drawing definitive conclusions about the efficacy and safety of abatacept in dcSSc.”
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