ACR 2020 | Daily Highlights

Targeting TYK2: Will there be a «new kid on the ground» for psoriatic arthritis therapy?

EFFICACY AND SAFETY OF DEUCRAVACITINIB (BMS-986165), AN ORAL, SELECTIVE TYROSINE KINASE 2 INHIBITOR, IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: RESULTS FROM A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Abstract: L03
Authors: Philip Mease et al.

» zum Abstract

Key content:
Deucravacitinib inhibits selectively TYK2 through an allosteric mechanism by binding to its regulatory domain. In this randomized, double-blind placebo-controlled phase 2 trial, deucravacitinib (6mg or 12mg once daily) was compared to placebo in patients with active psoriatic arthritis, up to 30% of patients were allowed despite previous use of a TNF inhibitor. The primary endpoint was the ACR20 response at week 16. 203 patients with active psoriatic arthritis were included in the trial, 66% of patients were using csDMARDs at baseline, 15% had previously failed to TNF inhibitors. A dose-dependent response was observed with an ACR20, 50 and 70 response in the 12mg dose of 62.7%, 32.8% and 19.4% of patients; 52.9%, 24.3% and 14.3% in the 6mg dose and 31.8%, 10.6% and 1.5% with placebo. An MDA response at week 16 was observed significantly more frequent with deucravacitinib in both doses versus placebo (22.9% and 23.9% versus 7.6%). Resolution of enthesitis was observed in more than half of the patients treated with deucravacitinib independent of the dose and this was significantly better than placebo (22.6%). No serious infections, thromboembolic events or other serious adverse events were observed in deucravacitinib-treated patients.

Relevance:
TYK2 is involved in signal transduction of various type I and type II cytokines. Deucravacitinib has previously shown to be effective in a phase 2 trial in plaque psoriasis resulting in a PASI75 at week 12 in 67-75% of patients who received at least 3mg twice daily. So do we need another treatment option for patient with PsA? The ACR responses in psoriatic arthritis tend to underestimate clinical efficacy as polyarthritis is less frequently being observed than in rheumatoid arthritis leaving "less room for improvement". In addition the MDA response suggests relevant clinical efficacy. The observation that no serious adverse events were reported suggests that deucravacitinib may represent a compound with good efficacy and a good safety profile. However, this needs to be confirmed in a clinical phase 3 trial.

Zusammenfassung und Kommentar von:
Prof. Dr. Andrea Rubbert-Roth
St. Gallen