TYK2 Inhibition Promising in Psoriatic Arthritis

Ella Castle

The oral tyrosine kinase 2 inhibitor deucravacitinib was effective for the treatment of active psoriatic arthritis in a phase II placebo-controlled trial. At week 16, only 31.8% of patients who had been randomized to receive placebo met the 20% response criteria of the American College of Rheumatology (ACR20), compared with […]

The oral tyrosine kinase 2 inhibitor deucravacitinib was effective for the treatment of active psoriatic arthritis in a phase II placebo-controlled trial.

At week 16, only 31.8% of patients who had been randomized to receive placebo met the 20% response criteria of the American College of Rheumatology (ACR20), compared with 52.9% of those receiving 6 mg of deucravacitinib per day (P=0.0134) and 62.7% of those given 12 mg per day (P=0.0004), reported Philip Mease, MD, of Swedish Medical Center and the University of Washington in Seattle.

In addition, ACR50 responses were observed at week 16 in 10.6% of the placebo group compared with 24.3% of the 6 mg group (P=0.0326) and 32.8% of the 12 mg group (P=0.0016), while ACR70 responses were seen in 1.5% of the placebo group compared with 14.3% (P=0.0044) of the 6 mg group and 19.4% of the 12 mg group (P=0.0003), he reported in a late-breaking poster session at the virtual annual meeting of the American College of Rheumatology.

Tyrosine kinase 2 is an intracellular kinase that mediates signaling by certain cytokines involved in the pathophysiology of psoriatic arthritis. “Deucravacitinib is a novel agent that selectively inhibits this kinase through an allosteric mechanism by binding to the regulatory domain of tyrosine kinase type 2, which differs from the JAK [Janus kinase] 1-3 inhibitors, which bind to the active site of the kinase domain,” Mease explained.

In an earlier phase II trial in plaque psoriasis, 67-75% of patients who were given deucravacitinib in dosages of 3 mg or higher twice daily had 75% improvements on their Psoriasis Area and Severity Index scores compared with 7% for placebo.

The current study in an ongoing 1-year trial that randomized 203 patients with psoriatic arthritis of at least 6 months’ duration and had at least three tender and swollen joints, C-reactive protein level of 3 mg/L or higher, and at least one psoriasis lesion of 2 cm or more.

Patients had previously had inadequate responses or were intolerant of nonsteroidal anti-inflammatory drugs, corticosteroids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), or one tumor necrosis factor (TNF) inhibitor. The primary endpoint was the ACR20 response at week 16.

Participants’ mean age was 49.8, and median duration of psoriatic arthritis was 4.5 years. At baseline, two-thirds of patients were using conventional DMARDs and 15% had been nonresponders to TNF inhibitors.

On the Health Assessment Questionnaire Disability Index, changes at week 16 were -0.11 in the placebo group compared with -0.37 in the 6 mg group (P=0.0020) and -0.39 in the 12 mg group (P=0.0008). On the Short Form 36 physical component for health-related quality of life, changes from baseline were 2.3 in the placebo group compared with 5.6 in the 6 mg group (P=0.0062) and 5.8 in the 12 mg group (P=0.0042).

Enthesitis resolution at week 16 was observed in 22.6% of the placebo group compared with 51.3% of the 6 mg group (P=0.0138) and 50% of the 12 mg group (P=0.0393).

Adverse events were reported in 42.4% of the placebo group and 65.7% of each of the deucravacitinib groups, Mease said. The most common adverse events were nasopharyngitis, sinusitis, headache, and rash, with most being mild to moderate. None of the patients receiving deucravacitinib had serious adverse events, including serious infections, herpes zoster, opportunistic infections, or thrombotic events.

Last Updated November 10, 2020

Disclosures

The study was sponsored by Bristol Myers Squibb (BMS).

Mease reported financial relationships with BMS, AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB.

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