From bench to bedside - is there a role of IL-17 drugs in rheumatoid arthritis?

ABSTRACT

Introduction

IL-17 has been described as a pro-inflammatory cytokine that is relevant in the seronegative spondylarthritides with IL-17 targeted therapies being licensed for their treatment.

There is evidence to demonstrate that IL-17 is found in RA joints and contributes to the pro-inflammatory cascade. This results in synovial hyperplasia and osteoclastogenesis thus causing joint destruction and bony erosions.

Areas covered

This review article summarizes trials that have studied the use of IL-17 targeted therapies in RA patients who have failed conventional synthetic disease-modifying therapy (C-DMARDS) and biologic DMARDS.

Expert opinion

The trials that have studied IL-17 inhibitors in RA patients have only shown a modest improvement in disease activity. In several trials, the primary endpoint was not achieved whilst in others, when comparing with existing licensed biologics for RA, did not demonstrate any superiority.

Tissue Necrosis Factor-alpha (TNF-α) likely plays more of a pivotal role in the pathogenesis of RA with IL-17 having a synergistic effect. Therefore, in our opinion, IL-17 inhibitors as an independent therapy for RA are less likely to provide a cost-effective benefit. There may be scope to potentially combine it with TNF-α-inhibitors (TNF-i), but this requires further research especially with the potential concerns related to increased immunosuppression.

KEYWORDS:

• IL-17 inhibitors
• rheumatoid arthritis
• TNF inhibitors
• biologics
• pathophysiology
• trials

Article highlights

• There is evidence to demonstrate that IL-17 is found in RA joints and contributes to the proinflammatory cascade.). It is cited to be a pro-inflammatory cytokine, which mediates joint and cartilage destruction.

• Various IL-17 targeted therapies have been studied in the management of RA in phase 2 and 3 trials.

• The results have only shown modest improvement in RA outcomes and when studied directly with existing licensed biologics, IL-17 inhibitors have not shown to be superior.

• It is unlikely that IL-17 targeted therapy will be a viable therapeutic option for RA management. There may be some benefit in combining it with TNF inhibitors, but this must be weighed against the risks of increased immunosuppression.

Key three messages

1. IL-17 inhibitors are not beneficial in C-DMARD non-responders.

2. Switching to IL-17 inhibitors from another biologic DMARD in non-responders is also not beneficial.

3. Combination with anti TNF therapy may be beneficial in suboptimal responders but risk and benefit rationale need to be considered.

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

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

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary materials.

Additional information

Funding

This paper was not funded.