Deucravacitinib showed sustained efficacy in the various outcomes in psoriatic arthritis and a unique and consistent safety profile.
Philip Mease, MD, takes an in-depth look into the Part B, long-term, 52-week, Phase 2 trial evaluating deucravacitinib, a novel, oral, selective, allosteric inhibitor of tyrosine kinase 2 (TYK2), as a potential treatment for psoriatic arthritis (PsA). Results of the trial, “Safety and Efficacy of Deucravacitinib, an Oral, Selective Tyrosine Kinase 2 Inhibitor, in Patients with Psoriatic Arthritis: 52-Week Results from a Randomized Phase 2 Trial,” were presented at American College of Rheumatology Convergence 2022. Mease is a rheumatologist and Director of Rheumatology Research at the Swedish Medical Center/Providence-St Joseph Health.
“In terms of background for deucravacitinib, a part of the reason why it's going to be a bigger deal at this meeting than it may have previously been is because it was recently approved by the US Food and Drug Administration (FDA) for the treatment of psoriasis,” Mease explained. “That's an already an unusual thing, in that the previous Janus kinases (JAKs) that had been approved in PsA, rheumatoid arthritis, and ankylosing spondylitis, kind of work in the skin aspects of psoriasis, but they're not spectacular the way interleukin-17 (IL-17) or IL-23 are.”
As a TYK2 inhibitor, deucravacitinib plays a prominent role in the signaling pathway in inhibiting IL-23, a key cytokine in the skin manifestations of psoriasis.
“The big question was whether deucravacitinib was going to be saddled with the same safety label as tofacitinib or upadacitinib because of the results of the ORAL Surveillance and that the safety label with those JAK inhibitors indicates that there is a slightly greater risk when compared with tumor necrosis factor (TNF) inhibitors for cardiovascular risk, malignancy risk, and risk of death,” Mease stated. “What surprised people a month and a half ago, when the FDA approval for psoriasis came through, was that the psoriasis division of the FDA said they were not going to require a Black Box Warning because they believed there may be a better safety profile with this specific TYK2 inhibitor compared to the rest of the JAKs.”
In Part A of the study, deucravacitinib was shown to be significantly more efficacious when compared with placebo. At week 16 (Part B), patients who did not achieve minimal disease activity (MDA) with deucravacitinib were switched to ustekinumab. The Psoriatic Arthritis Disease Activity Score (PASDAS) measured efficacy across a variety of clinical domains and any adverse events (AEs) were reported.
Decreases in mean PASDAS scores seen in Part A were maintained through week 52 in the deucravacitinib group. Additionally, clinical and patient-reported outcome improvements, including the Psoriasis Area and Severity Index (PASI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Disease Activity Index for Psoriatic Arthritis (DAPSA), and Patient Global Assessment of Disease Activity (PGA), were also sustained at the end of Part B.
The safety profile of deucravacitinib was comparable in both Part A and Part B. No opportunistic infections, malignancy, thrombotic events, herpes zoster, or treatment-related serious AEs were reported in the deucravacitinib cohort.
“Long story short, deucravacitinib showed sustained effectiveness in all the various outcomes in psoriatic arthritis and a profile a safety profile that appears to be relatively unique and consistent, which led to its approval in psoriasis already with a good safety label,” Mease concluded. “The key next step is finishing the phase 3 trial. We're proceeding with that quite nicely in multiple countries around the world in a much bigger trial in the phase 2 trial. There are also other indications, such as lupus, among others that are being thought about for this particular drug.”