The PAUSE Randomized Clinical Trial
The PAUSE trial was conducted to determine whether blocking CD28/B7 costimulatory signaling with abatacept would prevent relapse of psoriasis after effective treatment with ustekinumab (an IL12/23 antagonist). In an article published in JAMA Dermatology, the study team showed that relapse following ustekinumab discontinuation was not delayed by abatacept treatment, and was associated with a pathogenic IL-23-mediated molecular signature in skin lesions, which was unaffected by blockade of the CD28-CD80/86 costimulation pathway.
Other studies have shown that relapse is initiated by tissue-resident memory T (TRM) cells that are poised to produce IL-17A and IL-22. CD28 expression is highly variable in these cells further supporting the hypothesis that relapse is triggered in a CD28 independent mechanism. Understanding the mechanisms that regulate the reactivation of TRM cells and their key interactions with innate immune and stromal cell populations in recurring lesions may help identify new treatment strategies for durable remission in psoriasis and potentially other diseases.