James Krueger, MD, PhD | Rockefeller University | New York, NY

Dermatology Research Associates | Los Angeles, CA

Northwestern University | Chicago, IL

Tulane University | New Orleans, LA

University of Michigan | Ann Arbor, MI

Rockefeller University | New York, NY

Wake Forest University | Winston-Salem, NC

Case Western Reserve University | Cleveland, OH

The University of Utah | Salt Lake City, UT

Innovaderm Research | Montreal, QC

Kirk Barber Research | Calgary, AB

Psoriasis is a chronic T-cell mediated autoimmune disorder that causes inflammation of the skin and joints, often marked by skin rashes and plaques. Ustekinumab, a biologic that blocks the inflammatory cytokines IL-12 and IL-23, is effective at inducing disease remission and is approved for use in psoriasis. Although ustekinumab is effective in a large portion of patients, the benefits require ongoing administration of treatment. There are currently no known therapies for psoriasis that can induce long-lasting tolerance.

T cell activation requires two signals: antigen engagement with the T cell receptor plus a co-stimulatory signal, and evidence suggests that tolerance can be achieved by blocking the co-stimulatory signal. Abatacept is a biologic approved for use in rheumatoid arthritis that blocks this second, co-stimulatory signal. The goal of the PAUSE study is to first reduce inflammation and the number of activated T cells using ustekinumab, and then prevent subsequent re-activation of these cells by blocking co-stimulatory signals with abatacept. The sequential treatment strategy is designed to create an environment optimal for inducing durable changes to the immune system that lead to tolerance.

The PAUSE study is testing the combination of two biologics, ustekinumab (Janssen Biotech, Inc.) and abatacept (Bristol-Myers Squibb), in psoriasis patients. This trial will test whether the sequential combination of anti-IL12/23 (ustekinumab) and CTLA-4 Ig (abatacept) in psoriasis will produce changes in the immune system that will lead to durable disease remission.

PAUSE is a prospective two-arm trial that will be conducted at multiple sites around the country. The study will enroll up to 140 psoriasis patients in an open label lead-in ustekinumab phase, after which 80 patients who respond to treatment will be randomized to either abatacept plus ustekinumab placebo or continued ustekinumab plus abatacept placebo. Therapy will be discontinued after 39 weeks and patients will be followed out to week 88 to determine whether abatacept induces tolerance and prevents the psoriasis relapses. Investigators will also be able to examine pathways and signatures related to T cell tolerance directly in the affected tissue, something not always possible in other autoimmune disorders.