TY - JOUR
T1 - Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA)
T2 - results from a randomised, placebo-controlled, phase 2 trial
AU - van der Heijde, Désirée
AU - Baraliakos, Xenofon
AU - Gensler, Lianne S.
AU - Maksymowych, Walter P.
AU - Tseluyko, Vira
AU - Nadashkevich, Oleg
AU - Abi-Saab, Walid
AU - Tasset, Chantal
AU - Meuleners, Luc
AU - Besuyen, Robin
AU - Hendrikx, Thijs
AU - Mozaffarian, Neelufar
AU - Liu, Ke
AU - Greer, Joy M.
AU - Deodhar, Atul
AU - Landewé, Robert
N1 - Funding Information:
DvdH has received consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb (BMS), Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB and is the director of Imaging Rheumatology BV. XB has received grants or research support and consultation fees from AbbVie, BMS, Celgene, Chugai, Eli Lilly, Galapagos, Hexal, Janssen, Merck, Novartis, Pfizer, Sandoz, and UCB, outside of the submitted work. LSG has received grants from AbbVie, Amgen, Novartis, and UCB and consulting fees from Eli Lilly, Galapagos, Janssen, Novartis, and Pfizer during the conduct of the study. WPM has received personal fees from Galapagos during the conduct of the study, and grants and consulting fees from AbbVie, Janssen, Novartis, and Pfizer, and consulting fees from, Boehringer Ingelheim, Celgene, Eli Lilly, and UCB, outside of the submitted work. VT and ON have received fees for performance of this study from Galapagos. WA-S, CT, LM, RB, and TH are employees of and have received warrants from Galapagos during the conduct of the study. NM, KL, and JMG are employees of and hold stock, stock options, or shares with Gilead Sciences. AD has received consultancy fees from Galapagos during the conduct of the study, and consultancy fees from BMS and research grants and consultancy fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, outside of the submitted work. RL has received consulting fees from Galapagos during the conduct of the study, and consulting fees from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Merck, Pfizer, Roche, Schering, TiGenix, and UCB outside of the submitted work. RL is also a director of Rheumatology Consultancy BV.
Funding Information:
We thank the study investigators and patients who participated in this study. Individuals at Gilead Sciences were responsible for data management and statistics. The study was sponsored by Galapagos NV and co-funded by Galapagos NV and Gilead Sciences. Medical writing support (including development of drafts of the manuscript in consultation with the authors, assembling of tables and figures, collation of author comments, copyediting, fact checking, and referencing) was provided by Louise Niven at Aspire Scientific (Bollington, UK) and funded by Galapagos NV.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85055083813&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055083813&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(18)32463-2
DO - 10.1016/S0140-6736(18)32463-2
M3 - Article
C2 - 30360970
AN - SCOPUS:85055083813
VL - 392
SP - 2378
EP - 2387
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 10162
ER -