Abatacept following ustekinumab withdrawal does not prevent psoriasis relapse

Abatacept treatment after ustekinumab withdrawal did not prevent psoriasis relapse, according to a randomized clinical trial.

“Psoriasis vulgaris is a systemic immune-mediated disease that predominately involved the skin and joints. The pathogenesis involved activated interleukin (IL)17-producing T cells in skin, perpetuated by an IL-23-mediated psoriasis molecular signature that reflects the pathogenic keratinocyte response,” Kristina M. Harris, PhD, of the Immune Tolerance Network’s biomarker and discovery research group at the University of California, San Francisco, and colleagues wrote. “Ustekinumab is a U.S. Food and Drug Administration-approved biologic agent for psoriasis that targets the IL-12/IL-23 pathways. Ongoing administrations of ustekinumab is required because discontinuation leads to psoriasis relapse.”

The parallel-design, double-blind, placebo-controlled, randomized Psoriasis Treatment with Abatacept and Ustekinumab: a Study of Efficacy (PAUSE) trial included 108 adult psoriasis patients (mean age, 46.1 years; 67.6% men) who were treated with open-label ustekinumab at 10 sites in the U.S. and Canada.

The trial had three phases: a lead-in phase during which patients were treated with ustekinumab for 12 weeks; a randomized treatment phase during which 91 patients were randomly assigned to receive abatacept or ustekinumab for 28 weeks; and a 48-week observation phase.

Ustekinumab was administered at weeks 0 and 4 and patients who weighed 100 kg or less received 45 mg per dose, while those who weighed more than 100 kg received 90 mg per dose.

Those who achieved a 75% or greater improvement in Psoriasis Area Severity Index scores were eligible to be randomly assigned in the trial’s second phase. Those in the abatacept group received 125 mg subcutaneously, along with ustekinumab placebo, while those in the ustekinumab group received ustekinumab and abatacept placebo.

In the abatacept group, 41 of 45 subjects (91.1%) experienced psoriasis relapse before week 88, compared with 40 of 46 (87%) of those in the ustekinumab group (P = .41).

Between weeks 12 and 40 the abatacept group had a higher proportion relapse with 25 of 45 (55.6%) compared with 14 of 46 (30.4%) in the ustekinumab group (P = .01).

The median time from enrollment to relapse was 40 weeks for those in the abatacept group and 60 weeks for those in the ustekinumab group, whereas the median time to relapse from the last dose of ustekinumab was 36 weeks for the abatacept group and 32 weeks in the ustekinumab group.

“Early trials with abatacept in psoriasis and psoriatic arthritis suggested clinical benefiting cutaneous lesions, contributing to the idea that switching from ustekinumab to abatacept in psoriasis might induce T-cell tolerance in resolving lesions by means of costimulatory blockade,” the authors wrote. “However, the results of PAUSE as reported here showed that abatacept did not prevent relapse after ustekinumab withdrawal.”