Treatment with abatacept led to a reduction in skin stiffening and disability, as well as better overall health, in people with early diffuse cutaneous scleroderma (dcSSc) who participated in the yearlong Phase 2 ASSET trial and its six-month extension, new 18-month data show.
“Data from our trial provide hope for a potential future treatment,” according to the study’s scientists, who said abatacept “might promote” overall health improvements for dcSSc patients.
The study, “Safety and efficacy of abatacept in early diffuse cutaneous systemic sclerosis (ASSET): open-label extension of a phase 2, double-blind randomised trial,” was published in the journal The Lancet Rheumatology.
Activated immune T-cells have been implicated in the development of dcSSc, particularly in its hallmark skin manifestations.
Abatacept is currently approved as a treatment for rheumatoid arthritis, juvenile arthritis, and psoriatic arthritis under the name Orencia, marketed by Bristol-Myers Squibb. The treatment is a modified protein that reduces T-cell activation by blocking T-cell receptors.
ASSET — officially titled A Study of Subcutaneous Abatacept to Treat Diffuse Cutaneous Systemic Sclerosis — was a Phase 2 trial (NCT02161406) done in collaboration with Bristol-Myers Squibb that compared the efficacy and safety of a 125 mg dose of abatacept, given by under-the-skin injection, with a placebo over one year in participants with early stage dcSSc.
The results, previously reported, showed that abatacept lessened skin thickening as measured by the modified Rodnan Skin Score (mRSS). While this benefit was not statistically significant compared with the placebo group, the treated patients did show clinically meaningful improvements in functional ability and overall health.
At the trial’s completion, the ASSET participants had the option to enroll in an extension study for an additional six months, the results of which have now been reported by researchers.
Of the 88 patients starting ASSET, 67 — 34 who received a placebo and 33 who were treated with abatacept — transitioned to the extension part, in which all participants were given abatacept. A total of 32 participants in each group completed the assessments at the final 18-month mark.
Among patients receiving abatacept in ASSET, the mean reduction — which shows improvement — in mRSS from the study’s start was 6.6 points at one year. That score was further reduced, to a total of 9.8 points, at 18 months. For those initially given a placebo, the mRSS decreased by 3.7 points at 12 months. After switching to abatacept, this score was found to have dropped by a total of 6.3 points compared with the study’s start.
The proportion of participants whose mRSS scores dropped by five points or more at 12 months was 68% in those assigned to the abatacept group and 50% among those given a placebo. After the additional six months, those proportions increased to 72% in the group that continued abatacept treatment and to 65% among the patients who switched from the placebo.
In addition, scores on the Health Assessment Questionnaire-Disability Index (HAQ-DI) showed significant improvement at one year among those in the abatacept group, which contrasted with worsening seen in those receiving the placebo. These scores changed minimally during the extension portion.
A visual analog scale (VAS) for assessing pain showed no changes after 12 months in the abatacept group. At 18 months, such scores were improved regardless of abatacept treatment duration.
In contrast, a physician global assessment of VAS scores improved during ASSET among patients receiving abatacept, with a mean score decrease of 1·4 points compared with a lesser decrease in those given the placebo (0.3 points). These scores were maintained in the group staying on abatacept and improved in patients switching from placebo during the extension.
Median ACR-CRISS scores — a composite measure encompassing cardiopulmonary-renal involvement as well as mRSS changes, HAQ-DI, patient and physician global assessment, and a measure of lung function — were significantly better at month 12 in patients given abatacept than in those given a placebo. Both groups showed improvements during the extension part.
Specifically, an ACR CRISS score of 0.60 or higher — considered a clinically meaningful improvement — was achieved at one year in 55% of participants on abatacept compared with 36% of those given a placebo. After 18 months, the same score increase was found in 66% of patients on abatacept since the study’s start verus 50% of those who switched from receiving the placebo.
Physical function and anxiety, as measured by PROMIS-29 questionnaires, showed improvements in both groups during the extension. In addition, the criteria for low disease activity increased from 15% to 31% of patients assigned abatacept and declined from 16% to 13% of participants in the placebo–abatacept group.
Abatacept was well-tolerated throughout the first year, with more patients in the placebo group experiencing serious adverse events than the abatacept group. No new safety concerns were noted during the six-month extension, with adverse events occurring in fewer participants in both groups.
Infections occurred in nine patients in the placebo–abatacept group during the open-label extension phase and 11 patients in the abatacept–abatacept group. While two deaths were reported during the initial 12-month portion, caused by scleroderma renal crisis, no deaths were recorded during the open-label extension. Treatment-emergent adverse events leading to abatecept discontinuation included ventricular fibrillation with cardiac arrest, and an upper respiratory infection with night sweats.
Noting that the data “provide hope” for a potential future therapy, the researchers said a Phase 3 clinical trial “is necessary to definitively assess the safety and efficacy of abatacept” in dcSSc patients.
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