Phase 2 Trial Results for Sjögren’s Syndrome & SLE Presented in 2nd Plenary Session at ACR Convergence 2022

Marilyn Pike, MD, PhD

In another presentation, Marilyn Pike, MD, PhD, a rheumatologist in Raleigh, N.C., and president of MedPharm Consulting Inc., discussed encouraging efficacy and safety results from a phase 2 trial of the oral tyrosine kinase 2 (TYK2) inhibitor decravacitinib in moderate to severe systemic lupus erythematosus.¹⁰

A member of the Janus kinase (JAK) family of enzymes, TYK2 mediates the signaling of multiple key cytokines involved in lupus pathogenesis, including type I interferons, interleukin (IL) 10, IL-12 and IL-23. However, it does not participate in some of the pathways triggered by other members of the JAK family. For example, JAK 1, 2 and 3 respond to different immune cytokines, as well as extra-immune pathways related to hematopoiesis and lipid metabolism.¹¹

Tofacitinib and other existing JAK inhibitor drugs may cause changes in laboratory parameters such as hemoglobin, leukocytes and kidney and liver blood tests, partly due to the activation of these other pathways. In contrast, TYK2’s signaling profile may increase the safety of TYK2 inhibition relative to current JAK inhibitors.¹²

Deucravacitinib, an oral, selective inhibitor of TYK2, binds to a unique domain on the enzyme, locking it in its inactive state. A recent phase 2 study of deucravacitinib in psoriatic arthritis demonstrated promising safety and efficacy signals, and in September the FDA approved deucravacitinib for the treatment of moderate-to-severe psoriasis, making it the only TYK2 inhibitor approved for any indication.¹¹

PAISLEY Trial Results

Through the 48-week randomized, double-blind, placebo-controlled PAISLEY trial, Dr. Pike and colleagues sought to test the efficacy of the drug in active systemic lupus erythematosus.¹⁰ All participants had moderate to severe disease, measured by a score of at least six on the SLE Disease Activity Index 2000 (SLEDAI-2K), which assesses overall disease activity. All participants also had to have at least one severe or two moderate disease manifestations as assessed by the British Isles Lupus Assessment Group (BILAG), another lupus disease activity score.

The 363 participants were randomized into four groups—placebo or one of three different dose regimens of deucravacitinib: 3 mg twice a day, 6 mg twice a day or 12 mg once a day. Patients were required to be on background therapy with at least one antimalarial or immunosuppressant drug. Patients could receive up to 30 mg prednisolone or equivalent daily, but tapering to 7.5 mg day was required between weeks 8–20; another optional steroid taper took place between weeks 32 and 40.