JAK Inhibitors for Axial Spondyloarthritis: What does the Future Hold?

To discuss the potential role of JAK inhibitors (JAKis) as a new therapeutic class for the treatment of axial spondyloarthritis (axSpA, including ankylosing spondylitis [AS] and non-radiographic axSpA [nr-axSpA]).

A phase III randomized controlled trial of tofacitinib (a "pan JAKi") in patients with active AS was found to be superior to placebo in achieving the ASAS20 primary endpoint at week 16 (56.4% and 29.4%, p < 0.0001, phase II trials of AS). Upadacitinib, a JAK1 inhibitor, has also been evaluated in a phase III trial for its efficacy and safety in AS. The primary endpoint, ASAS40 at week 16, was reached by 52% of the patients randomized to upadacitinib and 26% of the patients receiving placebo (p = 0·0003). All the important secondary endpoints also improved with both agents. No new changes in their safety profile were noted. However, the more frequent occurrence of cardiovascular and cancer adverse events associated with tofacitinib than with TNFi observed in the very recent post-marketing "ORAL surveillance" safety study, the results of which were released on January 27, 2021, may lead to safety concerns swirling around the whole class of JAKis. JAKis seem to be effective in treating signs and symptoms of AS but have not been studied in nr-axSpA. Both tofacitinib and upadacitinib have been pre-registered with the FDA for the treatment of AS. Upadacitinib has just recently received approval for this indication in the European Union..