This is one of two phase 2 studies of filgotinib published in the Lancet that provides the first insight into the potential of a highly selective JAK1 inhibitor in two different spondyloarthritis conditions.
The TORTUGA trial reported that filgotinib was efficacious (mean ASDAS change from baseline to week 12 =1.47 vs.−0·57 in placebo group; p<0.0001) and safe for the treatment of patients with active ankylosing spondylitis who have not responded to first-line pharmacological therapy with NSAIDs.
According to a commentary, the findings of these studies should be interpreted with caution pending robust phase 3 studies that include active comparators, but acknowledges that they offer encouraging evidence that selective inhibition of JAK1, rather than broader inhibition across JAKs, might suffice in the management of spondyloarthritis. It notes that several other JAK inhibitors are under investigation for the treatment of immune-mediated inflammatory diseases, including baricitinib (JAK1/2) and upadacitinib (JAK1), with others to come, and as the armamentarium expands, more questions arise:
• At what stage in the therapeutic pathway will JAK inhibition provide optimal benefit? • Can the broader spectrum of cytokines blocked by these drugs, compared with monospecific biologics, confer deeper immune modulatory effects? • Will selective inhibition within the JAK family, or indeed targeting of other JAK members (e.g. TYK2), confer within-class therapeutic advantage? • How will these drugs modulate comorbidities that are prevalent in patients with spondyloarthritis?