BACKGROUND: At present, biological disease-modifying anti-rheumatic drugs 
(DMARDs) are the only treatment recommended for patients with ankylosing 
spondylitis who have not responded to first-line treatment with non-steroidal 
anti-inflammatory drugs (NSAIDs). The TORTUGA trial investigated the efficacy 
and safety of filgotinib, an oral selective Janus kinase 1 (JAK1) inhibitor, for 
the treatment of patients with active ankylosing spondylitis.
METHODS: In this completed, randomised, double-blind, placebo-controlled, phase 
2 trial, we enrolled adult patients from 30 sites in seven countries (Belgium, 
Bulgaria, Czech Republic, Estonia, Poland, Spain, and Ukraine). Eligible 
patients had active ankylosing spondylitis and an inadequate response or 
intolerance to two or more NSAIDs. Patients were randomly assigned (1:1) with an 
interactive web-based response system to receive filgotinib 200 mg or placebo 
orally once daily for 12 weeks. Randomisation was stratified by current use of 
conventional synthetic DMARDs and previous receipt of anti-tumour necrosis 
factor therapy. The patients, study team, and study sponsor were masked to 
treatment assignment. The primary endpoint was the change from baseline in 
ankylosing spondylitis disease activity score (ASDAS) at week 12, which was 
assessed in the full analysis set (ie, all randomised patients who received at 
least one dose of study drug). Safety was assessed according to actual treatment 
received. This trial is registered with ClinicalTrials.gov, number NCT03117270.
FINDINGS: Between March 7, 2017, and July 2, 2018, 263 patients were screened 
and 116 randomly assigned to filgotinib (n=58) or placebo (n=58). 55 (95%) 
patients in the filgotinib group and 52 (90%) in the placebo group completed the 
study; three (5%) patients in the filgotinib group and six (10%) in the placebo 
group discontinued treatment. The mean ASDAS change from baseline to week 12 was 
-1·47 (SD 1·04) in the filgotinib group and -0·57 (0·82) in the placebo group, 
with a least squares mean difference between groups of -0·85 (95% CI -1·17 to 
-0·53; p<0·0001). Treatment-emergent adverse events were reported in 18 patients 
in each group, the most common being nasopharyngitis (in two patients in the 
filgotinib group and in four patients in the placebo group). Treatment-emergent 
adverse events led to permanent treatment discontinuation in two patients (a 
case of grade 3 pneumonia in the filgotinib group and of high creatine kinase in 
the placebo group). No deaths were reported during the study.
INTERPRETATION: Filgotinib is efficacious and safe for the treatment of patients 
with active ankylosing spondylitis who have not responded to first-line 
pharmacological therapy with NSAIDs. Further investigation of filgotinib for 
ankylosing spondylitis is warranted.
FUNDING: Galapagos and Gilead Sciences.