According to the results of a randomized controlled trial published in Arthritis & Rheumatology, abatacept was safe for patients with diffuse cutaneous systemic sclerosis (dcSSc) but had little overall effect on skin thickness.
In this phase 2 double-blind placebo-controlled study, 88 patients with dcSSc were randomly assigned in a 1:1 ratio to receive either 125 mg subcutaneous abatacept or placebo for 12 months. Patients were stratified by disease duration (≤18 months vs >18-≤36 months) in the overall analysis. Study injections were administered weekly at home; patients attended in-clinic follow-up assessments at months 1, 3, 6, 9, and 12. The primary outcome measure was the change in modified Rodnan skin score (mRSS) from baseline to 12 months. As safety end points, investigators also monitored patients for adverse events. Linear mixed models were used to identify outcome differences between treatment groups. Skin biopsies were taken at baseline and processed for RNA; patients were then classified into different gene expression subsets. Outcome measures were also compared across these gene expression subsets.
Adjusted mean change in mRSS at 12 months was -6.24 units for patients receiving abatacept and -4.49 units for patients receiving placebo (P =.28). Overall, adjusted mean change in mRSS was not significant between groups. However, compared with placebo, the abatacept group experienced clinically and statistically significant improvements on the Health Assessment Questionnaire-Disability Index and a new composite end point, the American College of Rheumatology Combined Response Index in Systemic Sclerosis.
Compared with patients in the abatacept group, a greater percentage of patients receiving placebo required escape therapy (16% vs 36%). In the “Inflammatory” and “Normal-like” skin gene expression subsets, decline in mRSS over 12 months was greater in patients receiving abatacept than in patients receiving placebo (P <.001). A total of 35 patients in the abatacept group vs 40 patients in the placebo group had adverse events. Two deaths occurred in the abatacept group and 1 in the placebo group.
Abatacept for dcSSc was well-tolerated by patients, although the treatment did not meaningfully change mRSS over 12 months. Certain gene expression subsets displayed some evidence in favor of abatacept. These data warrant further exploration in a phase 3 trial.
Khanna D, Spino C, Johnson S, et al. Abatacept in early diffuse cutaneous systemic sclerosis – results of a phase 2 investigator-initiated, multicenter, double-blind randomized placebo-controlled trial [published online July 24, 2019]. Arthritis Rheumatol. doi:10.1002/art.41055