Upadacitinib for the treatment of adult patients with active psoriatic arthritis

ABSTRACT

Introduction

Psoriatic arthritis (PsA) is a rheumatic disorder that may be responsible for relevant articular impairment. The recently licensed Janus Kinase (JaK) inhibitors represent a new opportunity to improve PsA treatment. This review deals with the clinical usefulness of the selective JaK-1 inhibitor upadacitinib (UPA) in patients with PsA.

Covered areas

Two phase-III studies are available: SELECT-PsA 1, performed in patients with an inadequate response to non-biological therapies, and SELECT-PsA 2, conducted in biologic-experienced patients. Long-term extension results and post-hoc analysis data of these two trials are also available.

Expert opinion

The results provided by the trials indicate that UPA may be used to treat all of the clinical manifestations of PsA. Venous thromboembolism, cardiovascular events, and malignancy, the most feared adverse events associated with JaK inhibitor use, were not increased in the trial populations, yet long-term observational studies are needed to make sure that UPA is safe in this respect.

KEYWORDS:

• Psoriatic arthritis
• upadacitinib
• Janus Kinase inhibition
• SELECT-PsA
• treatment

Article highlights

• Psoriatic arthritis (PsA) is a rheumatic disorder with a detrimental effect on the health-related quality of life of the affected patients.

• Janus Kinase (JaK) inhibitors are a new class of small molecules that have proven to be efficacious for the treatment of rheumatoid arthritis (RA).

• Upadacinitib (UPA) is a selective JaK1 inhibitor recently licensed for the treatment of PsA.

• Two randomized controlled trials (SELECT-PsA 1 and 2), performed in PsA patients with an inadequate response to conventional synthetic drugs or biologics, have provided the data to support UPA use in PsA.

• The main results of these trials and of their long-term extensions are reported in this review.

• The efficacy results of the two trials indicate that UPA is more efficacious than placebo and comparable to adalimumab in improving all of the clinical manifestations of PsA.

• Both bio-naïve and bio-experienced PsA patients responded to UPA, but in the latter the response was numerically inferior.

• The safety profile which emerged from the two trials was similar to that expressed by RA trials, with no knew safety signals

• Upper respiratory tract infections were the most common adverse events and Herpes Zoster was the only infection more frequent in the UPA treated PsA patients.

• In the SELECTS-PsA trials, incidence rate of venous thromboembolism and major cardiovascular events was extremely low, nevertheless, given the reported increase of these events and of malignancies in RA patients treated with JaK inhibitors, long-term observational studies are needed to establish the safety of UPA in this respect.

Declaration of interest

A Marchesoni, has received speaker fees and consultancy honoraria from Abbvie, Lilly, Jannsen, Novartis, UCB. G Citriniti has received speaker fees and consultancy honoraria from Amgen, Biogen, Lilly, Galapagos, MSD. N Girolimetto has received speaker fees and consultancy honoraria from Lilly, Novartis. N Possemato has received speaker fees and consultancy honoraria from Abbvie, Amgen, Pfizer, Novartis, Lilly, Janssen, Galapagos, UCB. C Salvarani reports royalties from UpToDate, consultant fees from Boehringer-Ingelheim, Pfizer, Lilly, Amgen, CSL Vifor, Novartis.

Reviewer disclosure

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution

All authors contributed to drafting or critically revising the article for intellectual content and approved the final version of the article.

Additional information

Funding

This paper was not funded.