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Favorable phase 2 results with the TYK2 inhibitor for psoriatic arthritis at ACR 2020 coincided with announced positive phase 3 trial results for psoriasis.
Deucravacitinib, an oral selective tyrosine kinase 2 (TYK2) inhibitor, demonstrated benefit for active psoriatic arthritis (PsA) in a phase 2 trial reported at the American College of Rheumatology (ACR) Convergence 2020, coinciding with an announcement of positive phase 3 trial results in psoriasis.
Philip Mease, MD, Director of Rheumatology Research, Swedish Medical Center/Providence-St Joseph Health, and colleagues reported on the ongoing, one-year phase 2 trial.
“Deucravacitinib was efficacious versus placebo over 16 weeks of treatment in patients with active PsA,” investigators wrote. “Treatment was well tolerated and the safety profile was consistent with that observed in (earlier) phase 2 trial.”
In a coinciding statement manufacturer Bristol Myers Squibb indicated that deucravacitinib had been found superior to both placebo and an active comparator, apremilast, for patients with moderate to severe plaque psoriasis. A full evaluation and detailed results from the phase 3 trial data will be shared at a future medical meeting, according to the company.
In the statement deucravacitinib was described as “the first and only novel, oral, selective tyrosine kinsase 2 inhibitor in clinical studies across multiple immune-mediated diseases.”
Mease and colleagues contrasted the inhibition of TYK2 by deucravacitinib to inhibitors of the closely related janus kinases (JAK1-3). The TYK2 activation of Signal Transducer and Activator of Transcription (STAT)-dependent gene expression and cytokine responses are distinct from those activated by signaling kinases, and so presents a putatively unique target to interrupt cytokine pathways involved with pathology underlying immune-mediated disorders such as psoriasis.
At this stage in the phase 2 trial, 180 of 203 participants randomized 1:1:1 to receive placebo or either 6mg or 12mg of oral deucravacitinib daily have completed the 16-week course. Eligibility for the study included having a PsA diagnosis for at least 6 months; meeting CASPAR criteria; having active disease, with ≥3 tender and ≥3 swollen joints and at least 1 psoriatic lesion of ≥2cm; and C-reactive protein level ≥3mg/L (ULN, 5mg/L).
Mease and colleagues reported that both doses of the active drug met the primary outcome objective, demonstrating significantly greater ACR 20 responses compared to placebo at week 16 (52.9% of those receiving 6mg and 62.7% with 12mg, compared to 31.8% of those on placebo).
They characterize the finding as demonstrating a dose-response relationship. Of note, according to the announced early findings from the phase 3 study, the 6mg daily dose was superior to placebo and active comparator for psoriasis.
Investigators also reported that both doses of the active drug were superior to placebo in achieving secondary endpoints, and associated with generally similar results on measures including improvement from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI); Short Form-36 Physical Component Score (SF-36 PCS); the proportion of patients achieving ACR 50/70; HAQ-DI response, enthesitis resolution (Leeds Index).
The most common adverse events included nasopharyngitis, sinusitis, headache and rash; and most adverse events were graded as mild or moderate.There were no serious adverse events associated with active drug.
The study, "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" was presented at ACR 2020.