In patients with active ankylosing spondylitis (AS) whose disease did not respond adequately to nonsteroidal anti-inflammatory drugs (NSAIDs), filgotinib was safe, well tolerated, and efficacious, with superior results compared with placebo, according to findings published in The Lancet.
Investigators were interested in determining whether filgotinib, a targeted synthetic disease-modifying antirheumatic drug (DMARD) available in oral form, would be safe and effective as an additional option to biologic DMARDs, which require injections, for patients with AS with an inadequate response to NSAID therapy. This was the first study of its kind to examine the compound in the AS population.
The TORTUGA trial was a randomized, double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov identifier: NCT03117270) that compared filgotinib and placebo for the treatment of active AS unresponsive to treatment with ≥2 NSAIDs. A total of 116 participants were randomly assigned to receive oral filgotinib 200 mg (n=58; mean age, 41 years; 22% women) or placebo (n=58; mean age, 42 years; 29% women) once per day for 12 weeks.
The primary outcome was change in the AS Disease Activity Score (ASDAS) between baseline and 12 weeks. Secondary outcomes included the percentage of patients reaching 20% and 40% improvements in the Assessment of Spondyloarthritis International Society criteria (ASAS20 and ASAS40, respectively). Safety was evaluated by measuring the incidence of adverse events, particularly serious adverse events and treatment-emergent adverse events.
A total of 55 (95%) and 52 (90%) individuals in the filgotinib and placebo groups, respectively, completed the study. The filgotinib group demonstrated a mean ASDAS change at 12 weeks of -1.47, whereas the placebo group had a mean change of -0.57, yielding a least squares mean difference between groups of -0.85 (95% CI, -1.17 to -0.53; P <.0001). Major improvements in ASDAS scores were recorded for significantly more patients receiving filgotinib compared with placebo (33% vs 2%; P <.0001). The number of clinically significant ASDAS improvements was also higher in the filgotinib group (66% vs 26%; P <.0001).
Significantly more patients in the filgotinib group achieved ASAS20 (76% vs 40%; P <.0001) and ASAS40 (38% vs 19%; P =.019) responses compared with those in the placebo group. There were 18 (31%) participants from each group who reported treatment-emergent adverse events, of which nasopharyngitis was most common. As a result, 1 patient from each group had to discontinue treatment. No opportunistic infections, malignancies, extra-articular manifestations, active tuberculosis, or deaths were reported.
Study limitations included lack of a filgotinib dose-finding study prior to trial initiation, elevated C-reactive protein levels among many individuals at baseline that may have resulted in better responses, and a small sample size that limited subgroup analysis.
“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,” concluded the authors, who recommended that future research confirm the safety and efficacy of filgotinib using larger samples and longer follow-up periods.
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van der Heijde D, Baraliakos X, Gensler LS, et al. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomised, placebo-controlled, phase 2 trial [published online October 22, 2018]. Lancet. doi:10.1016/s0140-6736(18)32463-2