Malignancies and rheumatoid arthritis, csDMARDs, biological DMARDs, and JAK inhibitors: challenge and outlook

ABSTRACT

Introduction

Rheumatoid arthritis (RA) is an autoimmune disorder necessitating immunosuppressive therapy. Remarkable progress has been made in the treatment of RA over recent decades, particularly with the development of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi). Nonetheless, the development of new drugs has been accompanied by concerns regarding the association between these novel therapies and the risk of malignancy.

Areas covered

This narrative review aims to discuss the understanding of RA, conventional synthetic (cs) DMARDs, bDMARDs, JAKi, and their association with malignancy. Furthermore, the review discusses the management of malignancy in patients receiving b/tsDMARDs.

Expert opinion

Although recent studies suggest that the potential risk of malignancy of methotrexate and a JAKi tofacitinib, it is essential to avoid indiscriminate withholding of treatment by those agents, as this may lead functional impairment and increased mortality. Therefore, the adoption of a Treat-to-Target (T2T) approach considering individual patient characteristics, becomes of utmost importance. Rheumatologists should maintain a vigilant stance regarding malignancy in this context, recognizing the importance of early detection and management. Implementing a screening program for malignancies is indispensable, and the use of computed tomography screening may enhance the effectiveness of management strategies.

KEYWORDS:

• DMARDs
• Janus kinase inhibitors
• JAK inhibitors
• malignancy
• rheumatoid arthritis

Article highlights

• Patients with RA show a higher risk of malignancy compared to the general population.

• bDMARDs appear not to increase a risk of malignancy compared to csDMARDs.

• A study of the JAKi tofacitinib has demonstrated an increased risk of malignancy compared to TNFi, in patients aged 65 and above or those who have ever smoked.

• The adoption of malignancy management strategies within the framework of a Treat-to-Target (T2T) approach is highly advisable. A study suggested the utility of non-enhanced CT scans in the screening of the malignancy.

Declaration of interest

K. Sonomoto has received speaking fees from Astellas, Chugai, Eli-Lilly, Taisho-Toyama and a research grant from UCB-Japan. Y. Tanaka has received speaking fees or honoraria from Eli Lilly, AstraZeneca, AbbVie, Gilead, Chugai, Boehringer-Ingelheim, GSK, Eisai, Taisho, BMS, Pfizer, Taiho and has received research grants from Mitsubishi-Tanabe, Eisai, Chugai, Taisho. 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 apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have acted on advisory boards for AbbVie, Galapagos, Eli-Lilly and Pfizer in the last year. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.