Tofacitinib for the treatment of rheumatoid arthritis: an update

ABSTRACT

Introduction: Tofacitinib inhibits the Janus kinases, tyrosine kinases that are activated by cytokines involved in the pathophysiology of rheumatoid arthritis.

Areas covered: Clinical trials have revealed an anti-rheumatic effect of monotherapy and combination therapy with methotrexate (MTX). Post-hoc analysis of those clinical trials and real-world experiences will be reviewed to explore efficacy and safety.

Expert commentary: The efficacy of tofacitinib monotherapy has garnered much attention and has been initiated in large number of patients. However, combination therapy with MTX is necessary in order to achieve the maximum effect. Combination therapy can be transferred to monotherapy by tapering and/or discontinuing MTX. The discontinuation of tofacitinib should be avoided and tapering should be investigated. There has been no new safety signal although venous thrombotic events (VTEs) have been raised and would require long-term follow-up. Increased events of Herpes zoster were observed and the use of a subunit vaccination is expected to become an effective tool for prevention. Post-hoc analysis of the clinical trials and real-world experience is revealing further usefulness of tofacitinib not only in rheumatoid arthritis but also other diseases. Additional experience and data from the real world are required to help improve the use of tofacitinib..

KEYWORDS:

• Tofacitinib
• Janus kinase
• herpes zoster
• venous thromboembolism
• rheumatoid arthritis
• tofacitinib
• real-world

Key issues

• Tofacitinib monotherapy is emerging in clinical practice although combination therapy with MTX is required for the maximum anti-rheumatic effect.

• Safety is the most important issue to overcome, and this can only be solved by long-term follow-ups of the real-world clinical practice.

• Long-term follow-ups of patients from the clinical trials provided no new safety data, including malignancies. However, being the first in class with a completely new mechanism of action, a maximum effort to screen malignancies at the time of initiation could be important.

• HZ increased with tofacitinib compared to preexisting DMARDs and the subunit vaccine will possibly lead to a full settlement. However, the effect of the adjuvant system on RA is entirely unknown.

• Efficacy for an array of inflammatory and autoimmune diseases is under investigation, and additional case reports indicate efficacy in other disorders which could be formally investigated.

Declaration of interest

K Yamaoka has been a consultant for Abbvie, Pfizer, Gilead G.K., Asahikasei Pharma Corp., Astellas Pharma Inc., Eli Lilly Japan K.K, Japan Tobacco Inc.; on the speakers bureau for Astellas, Bristol-Myers Squibb, Chugai, Eisai Co Ltd, Eli Lilly Japan K.K, GSK, Janssen, Mitsubishi-Tanabe Pharma, Pfizer, Takeda; and has received research funding from Bristol-Myers Squibb, Chugai, GSK, Mitsubishi-Tanabe Pharma. 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 received research grants and has served as consultant (advisory boards) from Pfizer. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose. Pfizer provided a scientific accuracy review at the request of the journal editor.

Additional information

Funding

This paper was not funded.