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Investigators reported that a higher proportion of participants in the abatacept group relapsed between weeks 12 and 40 compared to participants in the ustekinumab group.
Data from the Psoriasis Treatment with Abatacept and Ustekinumab: a Study of Efficacy (PAUSE) clinical trial suggested that abatacept did not prevent psoriasis relapse in patients with moderate to severe plaque psoriasis, as it did not completely block the pathogenic psoriasis molecular pathways that led to relapse.
Investigators led by Kristina M. Harris, PhD, Biomarker and Discovery Research, University of California, San Francisco, noted that the biologic agent ustekinumab had been approved by the US Food and Drugs Administration (FDA) for the management of psioriasis.
However, ongoing administration of the biologic was required since discontinuation led to psoriasis relapse.
In earlier reports, abatacept was linked to improved skin lesions in a phase 2 psoriatic arthritis trial. It was also known to inhibit T-cell activation and function.
As such, Harris and colleagues hypothesized that costimulatory blockade with abatacept could induce tolerance in pathogenic T cells encountering antigen in resolving psoriasis lesions, leading to long-term remission.
The PAUSE trial was a multicenter parallel-design, double-blind, placebo-controlled randomized clinical trial that was conducted at 10 investigational sites in the United States and Canada.
Enrollment for the trial opened on March 19, 2014 and concluded on April 11, 2016. A total of 91 adults with moderate to severe plaque psoriasis were included in the study.
The trial consisted of a lead-in phase (weeks 0-12), a randomized treatment phase (weeks 12-40), and an observation phase (weeks 40-88).
Participants with moderate to severe plaque psoriasis received subcutaneous ustekinumab at weeks 0 and 4 during the lead-in phase.
Participants who weighed 100 kg or less received 45 mg per dose, while participants who weighed more received 90 mg per dose.
At week 12, the response to ustekinumab was assessed using the Psoriasis Area and Severity Index (PASI). Participants were eligible for randomization if they achieved 75% or greater improvement from baseline.
The 91 eligible participants were then randomized into 2 groups, 1 of which continued ustekinumab use while the other switched to abatacept.
The ustekinumab group received ustekinumab at weeks 16 and 28 and abatacept placebo weekly from weeks 12 to 39, and the PASI was assessed every 4 weeks until the final study visit.
Statistical analyses were performed in both the safety sample and intention-to-treat (ITT) sample.
The primary endpoint was treatment group comparisons for the proportion of ITT participants who were experiencing a psoriasis relapse between weeks 12 and 88, which were performed using a logistic regression model with the participant’s relapse status as the dependent variable and treatment group as the independent variable.
Harris and investigators reported that more participants in the abatacept groups experienced a psoriasis relapse before week 88 compared with participants in the ustekinumab group (41 of 45 [91.1%] vs 40 of 46 [87.0%]; P = .41).
Additionally, the psoriasis relapse rate did not decrease in the abatacept group compared with the ustekinumab group, and the primary endpoint of psoriasis relapse between weeks 12 and 88 was not met.
The investigators also acknowledged that a higher proportion of participants in the abatacept group relapsed between weeks 12 and 40 compared to participants in the ustekinumab group (25 of 45 [55.6%] vs 14 of 46 [30.4%]; P = .01).
Finally, abatacept did not maintain suppression of the pathogenic IL-23-mediated psoriasis molecular signature in lesions after ustekinumab withdrawal, and serum IL-19 levels increased.
“Evaluation of the pathogenic psoriasis molecular signature demonstrated that clinical relapse may involve compensatory T-cell activation pathways in the presence of CD28-CD80/CD86 blockade,” the team wrote.
The study, “Endpoint of Costimulatory Blockade with Abatacept After Ustekinumab Withdrawal in Patients with Moderate to Severe Plaque Psoriasis,” was published online in JAMA Dermatology.