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

Désirée van der Heijde, Xenofon Baraliakos, Lianne S. Gensler, Walter P. Maksymowych, Vira Tseluyko, Oleg Nadashkevich, Walid Abi-Saab, Chantal Tasset, Luc Meuleners, Robin Besuyen, Thijs Hendrikx, Neelufar Mozaffarian, Ke Liu, Joy M. Greer, Atulya (Atul) Deodhar, Robert Landewé

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalThe Lancet
DOIs
StateAccepted/In press - Jan 1 2018

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Janus Kinase 1
Ankylosing Spondylitis
Placebos
Safety
Therapeutics
Antirheumatic Agents
Anti-Inflammatory Agents
Pharmaceutical Preparations
Nasopharyngitis
Estonia
Ukraine
Bulgaria

ASJC Scopus subject areas

  • Medicine(all)

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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. / van der Heijde, Désirée; Baraliakos, Xenofon; Gensler, Lianne S.; Maksymowych, Walter P.; Tseluyko, Vira; Nadashkevich, Oleg; Abi-Saab, Walid; Tasset, Chantal; Meuleners, Luc; Besuyen, Robin; Hendrikx, Thijs; Mozaffarian, Neelufar; Liu, Ke; Greer, Joy M.; Deodhar, Atulya (Atul); Landewé, Robert.

In: The Lancet, 01.01.2018.

Research output: Contribution to journalArticle

van der Heijde, D, Baraliakos, X, Gensler, LS, Maksymowych, WP, Tseluyko, V, Nadashkevich, O, Abi-Saab, W, Tasset, C, Meuleners, L, Besuyen, R, Hendrikx, T, Mozaffarian, N, Liu, K, Greer, JM, Deodhar, AA & Landewé, R 2018, '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', The Lancet. https://doi.org/10.1016/S0140-6736(18)32463-2
van der Heijde, Désirée ; Baraliakos, Xenofon ; Gensler, Lianne S. ; Maksymowych, Walter P. ; Tseluyko, Vira ; Nadashkevich, Oleg ; Abi-Saab, Walid ; Tasset, Chantal ; Meuleners, Luc ; Besuyen, Robin ; Hendrikx, Thijs ; Mozaffarian, Neelufar ; Liu, Ke ; Greer, Joy M. ; Deodhar, Atulya (Atul) ; Landewé, Robert. / 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. In: The Lancet. 2018.
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abstract = "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.",
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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, Atulya (Atul)

AU - Landewé, Robert

PY - 2018/1/1

Y1 - 2018/1/1

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.

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