The infection risks of JAK inhibition

ABSTRACT

Introduction

Janus Kinase inhibitors (JAKi) have shown to be highly effective in the treatment of immune-mediated inflammatory diseases. As with all immunomodulatory therapies, careful assessment of any treatment-associated infection risk is essential to inform clinical decision-making.

Areas covered

We summarize current literature on infection rates among the licensed JAKi using published phase II/III trial results, post-licensing and registry data.

Expert opinion

licensed JAKi show increased risk of infection across the class compared to placebo, most commonly affecting respiratory and urinary tracts, nasopharynx and skin. This risk is dose-dependent. Risks are similar at licensed JAKi doses to that seen with biologic therapies. The risk is compounded by other risk factors for infection, such as age and steroid co-prescription. Herpes zoster reactivation is more common with JAKi compared to other targeted immune modulation, making screening for varicella exposure and vaccination in appropriate cohorts an advisable strategy. Crucially, these small risk increases must be balanced against the known harms (including infection) of uncontrolled autoimmune disease. JAKi are a safe and potentially transformative treatment when used for appropriately selected patients.

KEYWORDS:

• Adults
• Adverse events
• inflammatory disease
• JAK inhibitors
• older adults
• serious infections
• tuberculosis
• vaccination
• varicella zoster

Article highlights

• Serious infections are reported with licensed JAK inhibitors with a risk comparable to biologics.

• Herpes zoster is the most recognized opportunistic infection, the majority of cases are non-serious and uncomplicated.

• Vaccines are an important tool in preventing infection; varicella zoster virus (VZV) live vaccines should be avoided in VZV naïve patients.

Declaration of interest

J Galloway has received honoraria/speaker fees from Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UCB. 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 disclosure

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

Author contribution

All authors have contributed to the preparation of this review and meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship. All authors agree for the final version of the manuscript to be published.

Rights and permission

All figures and tables included in this article are original.

Additional information

Funding

This paper was not funded.