Are JAK Inhibitors the Next Big Advance in Spondylitis Treatment?

A Promising New Class of Small Molecule Therapy for Spondyloarthritis.

by Dr. David Borenstein M.D. 1/2019

Janus kinase (JAK) inhibitors are new class of small molecules that are taken orally that are regulators of the immune response. As opposed to biologic therapies that inhibit one cell signal (cytokine), JAK inhibitors blockade a variety of intracellular cell signaling pathways. This family of cytokines including JAK1, JAK2, JAK3, and Tyrosine Kinase 2 can form a variety of combinations that transmit signals from the cell surface to the cell nucleus. These signals result in the production of a range of factors that are important in the development of an inflammatory response.

The TORTUGA study is an investigation of the effectiveness of filgotinib, a selective Janus Kinas 1 inhibitor in the treatment of patients with active ankylosing spondylitis (AS) in individuals who had failed at least 2 nonsteroidal anti-inflammatory drugs. A total of 116 randomly assigned AS patients were treated, 58 received 200 mg of filgotinib and 58 received placebo in this phase 2 clinical trial. At 12 weeks, the filgotinib group had significant improvement compared to the placebo group as measured by an AS activity score along with other secondary outcomes. The adverse events were rare in both the filgotinib and placebo groups. The active group noticed improvement within a week of starting therapy.

TORTUGA is a phase 2 trial. A full phase 3 trial with more participants is ongoing to determine if filgotinib will be effective as a new therapy for AS. This initial trial suggests that JAK 1 inhibitors will be a new category of therapy for AS patients who are not improved by nonsteroidal and biologic agent treatment.

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  1. van der Heijde D et al. Efficacy and safety of filgotinib, a selective Jasnus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomized, placebo-controlled, phase 2 trial. Lancet 2018;392:2378-2387

David Borenstein, MD
Executive Editor