medwireNews: Findings from the phase II TORTUGA trial suggest that treatment with the Janus kinase (JAK)1 inhibitor filgotinib may be beneficial for patients with ankylosing spondylitis who have not responded to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs).
“The findings of our study might ultimately lead to an increase in the number of treatment options with alternative mechanisms of action available for patients with ankylosing spondylitis,” write Désirée van der Heijde (Leiden University Medical Center, the Netherlands) and colleagues in The Lancet.
The investigators report that the 58 patients with an inadequate response or intolerance to two or more NSAIDs who were randomly assigned to receive filgotinib (200 mg/day for 12 weeks) experienced a significantly greater reduction in disease activity than their 58 counterparts who were given placebo.
Specifically, the average reduction in ASDAS from baseline to week 12 was 1.47 points for patients treated with filgotinib versus 0.57 points for those in the placebo group, translating into a significant least-squares mean difference between the groups of 0.85 points.
The majority of patients in the filgotinib and placebo groups (97% and 95%, respectively) were treated with at least one concomitant medication during the study, most commonly NSAIDs.
van der Heijde and colleagues note that “the onset of therapeutic effect with filgotinib was rapid,” with improvements in disease activity observed after 1 week of treatment, and that 66% of filgotinib-treated patients experienced a clinically significant improvement in ASDAS by week 12 (decrease from baseline ≥1.1 points), compared with 26% of those in the placebo group.
“The safety profile of filgotinib in patients with ankylosing spondylitis was consistent with that described in clinical trials in patients with other indications,” say the researchers. An identical proportion of patients in both groups experienced treatment-emergent adverse events (TEAEs), at 31%, and nasopharyngitis was the most commonly reported TEAE in both the filgotinib and placebo study arms.
“The results of this study add to the weight of evidence supporting the benefit of selective JAK1 inhibition by filgotinib in a range of inflammatory diseases,” write the TORTUGA investigators.
And the authors of an accompanying comment agree, noting that that the findings “offer encouraging evidence that selective inhibition of JAK1, rather than broader inhibition across JAKs, might suffice in the management of spondyloarthritis.”
However, Iain McInnes and Stefan Siebert, both from the University of Glasgow in the UK, caution that the TORTUGA results “should be interpreted with caution pending robust phase 3 studies that include active comparators.”
The commentators conclude that “head-to-head comparisons are needed to consolidate the findings, as are larger sample sizes, longer follow-up, and more detailed exploration of clinically relevant patient subgroups (eg, those with a history of treatment with biological therapies).”
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