Upadacitinib for the treatment of adults with active non-radiographic axial spondyloarthritis (nr-axSpA)

ABSTRACT

Introduction

Non-radiographic axial spondyloarthritis (nr-axSpA) is a chronic inflammatory condition with axial and peripheral musculoskeletal involvement, fulfilling criteria of axSpA in the absence of advanced radiographic sacroiliitis. While appropriate treatment is required for chronic pain and disability resulting from disease progression, the limited availability of treatment options becomes evident. Upadacitinib, an oral selective Janus kinase 1 inhibitor, was approved in Europe, the United States, and other countries for management of nr-axSpA with inadequate response to existing therapies.

Area covered

This review summarizes essential drug profiles, efficacy, and safety of upadacitinib for nr-axSpA in conjunction with data pertaining to radiographic axSpA.

Expert opinion

In a phase 3 trial, upadacitinib exhibited efficacy for patients with nr-axSpA, irrespective of prior exposures to biological disease-modifying antirheumatic drugs (bDMARDs). The safety profiles of upadacitinib in nr-axSpA mirrored those in other indications, underscoring its potential as a promising treatment option for nr-axSpA. Concurrently, physicians should be aware of the absence of real-world data, longitudinal efficacy and safety, direct comparative studies between upadacitinib and bDMARDs in nr-axSpA, and evidence for precision medicine to identify patients who may optimally benefit from upadacitinib over bDMARDs. Future research is imperative to facilitate the effective utilization of upadacitinib in daily clinical practice.

KEYWORDS:

• Axial spondyloarthritis
• Janus kinase inhibitor
• non-radiographic axial spondyloarthritis
• rheumatology
• spondyloarthritis
• upadacitinib

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Correction

Article highlights

• Non-radiographic axial spondyloarthritis (nr-axSpA) refers to a chronic inflammatory condition affecting the spine or sacroiliac joints without advanced radiographic sacroiliitis.

• Despite nr-axSpA imposing a significant disease burden, pharmacological interventions have remained restricted to non-steroidal anti-inflammatory drugs and subsequent biological Disease-modifying antirheumatic drugs (bDMARDs), such as tumor necrosis factor inhibitors or interleukin-17 inhibitors. A certain number of patients with nr-axSpA fail to respond to these treatments, necessitating further treatment options.

• Upadacitinib is a Janus kinase (JAK) inhibitor preferentially targeting JAK1, which received approval from European Medicines Agency and the United States Food and Drug Administration in 2022.

• Upadacitinib is primarily metabolized via Cytochrome P450 (CYP) 3A4. Strong CYP3A4 inducers (e.g. rifampin) and inhibitors (e.g. clarithromycin) may reduce or increase the serum concentration of upadacitinib. No dosage adjustment is required in patients with renal dysfunction or mild to moderate liver dysfunction. Upadacitinib is NOT recommended for patients with end-stage renal disease (estimated glomerular filtration rate <15 mL/min/1.73 m²) or severe hepatic impairment (Child-Pugh C).

• In the phase 3 trial (SELECT-AXIS 2 nr-axSpA study), upadacitinib demonstrated adequate efficacy in patients with nr-axSpA, regardless of prior bDMARDs use. The safety profiles paralleled those in patients diagnosed with other conditions (e.g. rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis).

• Upadacitinib emerged as a promising therapeutic option for nr-axSpA. However, physicians should be aware of the lack of real-world data, data on long-term efficacy and safety, head-to-head trials between upadacitinib and bDMARDs, and evidence for precision medicine, particularly on patients for whom we should prioritize upadacitinib over bDMARDs. Further studies are imperative to utilize upadacitinib effectively in daily clinical practice.

Information resources

● ClinicalTrials.gov:

https://clinicaltrials.gov

● European Medicine Agency (EMA):

https://www.ema.europa.eu/en

● Pharmaceuticals and Medical devices Agency (PMDA) (Japanese):

http://www.pmda.go.jp

Declaration of interest

M Kishimoto received consulting fees and/or speaker fees from AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis. The authors have no other 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

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

Scientific accuracy review

AbbVie provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

This paper was not funded.