Targeted synthetic pharmacotherapy for psoriatic arthritis: state of the art

ABSTRACT

Introduction

In recent years, different studies regarding psoriatic arthritis (PsA) have shown the pathogenetic role of dysfunction of signaling pathways involving the phosphodiesterase-4 enzyme and transcription factors or enzymes belonging to the kinase (JAK)–signal family pathway. These also represent the target of several drugs known as targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs).

Areas covered

The authors performed a systematic literature search using the PubMed database, as well as through retrieving data from randomized controlled trials, their post-hoc analysis, and pooled data analysis on the efficacy and safety profile of the PDE4 inhibitor (PDE4i), apremilast, and the inhibitors of JAK (JAKis), tofacitinib, filgotinib, baricitinib, and upadacitinib, in PsA.

Expert opinion

In PsA, the PDE4i, apremilast, and the JAKi, tofacitinib, are effective across multiple clinical domains and have an acceptable tolerability profile, thus expanding the treatment options available for PsA patients. Apremilast and tofacitinib show several advantages mainly represented by their oral administration, a fast onset of action, and a short half-life. Data on tsDMARDs in PsA are still limited, and randomized trials and real-life studies are advocated.

KEYWORDS:

• Apremilast
• filgotinib
• Janus kinase
• JAK-inhibitors
• oral small molecules
• psoriatic arthritis
• phosphodiesterase-4
• tofacitinib
• tsDMARDs

Article highlights

• Psoriatic arthritis (PsA) is an inflammatory arthritis, associated with psoriasis, in which different pro-inflammatory cytokines and pathways contribute to induce and maintain the process.

• The disease represents a chronic condition, and there is the need for effective therapies with a favorable long-term safety.

• The recent introduction of tsDMARDs represents a relevant benefit in the management of patients who are unresponsive or who have contraindications to csDMARDs and bDMARDs

• The tsDMARDs PDE4i, apremilast, and the JAKi, tofacitinib, are effective across multiple PsA domains and with an acceptable tolerability profile, thus expanding the treatment options available for PsA patients.

• In the next years, the availability of multiple intracellular agents could ensure the possibility of a tailored and personalized therapy.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One referee declares having received honoraria and research grants from Celgene, and honoraria from Pfizer Inc. They have also received grants from AbbVie as well as honoraria from Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Hansen Pharmaceutical Ltd., Novartis and UCB Pharma. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was not funded.