Phase 2 Study Shows Promising Results for Deucravacitinib in PsA

EULAR 2022 (VIRTUAL)—Tyrosine kinase 2 (TYK2) is an intracellular kinase in the Janus kinase (JAK) family that mediates the signaling of multiple cytokines, including interleukin (IL) 23, IL-12 and type 1 interferons, which are integral to the immunopathogenesis of psoriatic arthritis (PsA). Deucravacitinib is an oral, selective intracellular JAK inhibitor that, at therapeutic doses, does not inhibit JAK1, JAK2 or JAK3.^1,2 The agent is currently being evaluated in global clinical trials to treat diseases including PsA, psoriasis, lupus and inflammatory bowel diseases.

In a phase 2 trial, deucravacitinib proved significantly more efficacious for achieving minimal disease activity in patients with active PsA after 16 weeks than placebo. This data was presented by Arthur Kavanaugh, MD, a rheumatologist and professor of medicine at the University of California, San Diego, La Jolla, Calif., during the 2022 Congress of the European Alliance of Associations for Rheumatology (EULAR), June 1–4, Copenhagen, Denmark.

This double-blind, multicenter study (NCT03881059) evaluated the effects of deucravacitinib on individual components of minimal disease activity. Minimal disease activity was defined as achieving five of the seven following criteria:

• A tender joint count of ≤1;
• A swollen joint count of ≤1;
• Tender entheseal points of ≤1;
• Patient global assessment of disease activity score of ≤20;
• A patient global assessment of pain score of ≤15;
• A Health Assessment Questionnaire-Disability Index (HAQ-DI) score of ≤0.5; and
• A Psoriasis Area and Severity Index [PASI] score of ≤1 or body surface area [BSA] of ≤3%.

The study enrolled 203 patients with a PsA diagnosis of at least six months who fulfilled Classification Criteria for PsA at screening and had active joint disease in at least three tender and swollen joints, high-sensitivity C-reactive protein (CPR) of at least 3 mg/L and at least one plaque psoriasis lesion of at least 2 cm. To participate in the study, patients also had to be either intolerant to or experienced ineffective treatment with at least one nonsteroidal anti-inflammatory drug (NSAID), one conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) and/or one tumor necrosis factor (TNF) inhibitor.

Patients were randomized in a 1:1:1 ratio to receive either 6 mg of deucravacitinib once daily, 12 mg of deucravacitinib once daily or placebo. The percentage of patients who achieved minimal disease activity and the proportion of patients who achieved each of component of minimal disease activity, minimal disease activity responders and nonresponders were assessed through week 16.

The Results

Of the 203 patients who were randomized, 180 patients completed the 16-week study, including 88% of the placebo group (n=58 of 66 patients), 90% of the 6 mg of deucravacitinib group (n=63 of 70 patients) and 88% of the 12 mg of deucravacitinib group (n=59 of 67 patients). The patient demographics and baseline disease characteristics were relatively similar across all three groups.

At baseline, no patient met five of the seven criteria required to be classified as having minimal disease activity. However, several of the individual components of minimal disease activity were achieved. Example: The criteria for tender entheseal points of ≤1 was met by 57.6% of patients who received placebo, 64.3% of patients who received 6 mg of deucravacitinib and 65.7% of patients who received 12 mg of deucravacitinib.

At week 16, 7.6% of patients who received placebo, 22.9% of patients who received 6 mg of deucravacitinib and 23.9% of patients who received 12 mg of deucravacitinib achieved minimal disease activity. Deucravacitinib treatment compared with placebo treatment led to a numerically greater mean reduction in all minimal disease activity components compared with baseline. Additionally at week 16, more patients treated with deucravacitinib achieved the threshold levels for each minimal disease activity component than patients who received placebo.

This study showed that patients treated for 16 weeks with deucravacitinib achieved higher rates of minimal disease activity than patients who received placebo. This agent is on its way to proving its effectiveness for managing patients with PsA and other immune-mediated diseases. It may soon be added to the armamentarium for these disorders.

References

1. Kavanaugh A, Coates L, Merola JF et al. Deucravacitinib an oral, selective tyrosine kinase 2 inhibitor, in a phase 2 trial in psoriatic arthritis: Achievement of minimal disease activity and its components [POS1039]. Ann Rheum Dis. 2022; 81(suppl 1):835.
2. News release: New two-year deucravacitinib data reinforce durable efficacy and consistent safety profile in treatment of moderate to severe plaque psoriasis. Bristol Myers Squibb. 2022 May 12.