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

Volumn 392, Issue 10162, 2018, Pages 2378-2387

  van der Heijde, Désirée ^a   Baraliakos, Xenofon ^b   Gensler, Lianne S ^c   Maksymowych, Walter P ^d   Tseluyko, Vira ^e   Nadashkevich, Oleg ^f   Abi Saab, Walid ^g   Tasset, Chantal ^g   Meuleners, Luc ^g   Besuyen, Robin ^h   Hendrikx, Thijs ^h   Mozaffarian, Neelufar ⁱ   Liu, Ke ⁱ   Greer, Joy M ⁱ   Deodhar, Atul ^j   Landewé, Robert ^k,l  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^b RUHR UNIVERSITY BOCHUM   (Germany)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF ALBERTA   (Canada)

^e KHARKIV MEDICAL ACADEMY OF POSTGRADUATE EDUCATION   (Ukraine)

^f DANYLO HALYTSKY LVIV NATIONAL MEDICAL UNIVERSITY   (Ukraine)

^g GALAPAGOS NV   (Belgium)

^h Galapagos BV   (Netherlands)

ⁱ GILEAD SCIENCES   (United States)

^j OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^k ACADEMIC MEDICAL CENTER   (Netherlands)

^l Zuyderland Medical Centre   (Netherlands)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CREATINE KINASE; DISEASE MODIFYING ANTIRHEUMATIC DRUG; FILGOTINIB; NONSTEROID ANTIINFLAMMATORY AGENT; TUMOR NECROSIS FACTOR INHIBITOR; ANTIRHEUMATIC AGENT; JAK1 PROTEIN, HUMAN; JANUS KINASE 1; JANUS KINASE INHIBITOR; PYRIDINE DERIVATIVE; TRIAZOLE DERIVATIVE;

ADULT; ADVERSE OUTCOME; ANKYLOSING SPONDYLITIS; ANKYLOSING SPONDYLITIS DISEASE ACTIVITY SCORE; ARTICLE; CONTROLLED STUDY; CREATINE KINASE BLOOD LEVEL; DEEP VEIN THROMBOSIS; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG SAFETY; DRUG WITHDRAWAL; FEMALE; HEMOGLOBINOPATHY; HUMAN; MAJOR CLINICAL STUDY; MALE; NEUTROPENIA; ONLINE SYSTEM; PATIENT ASSESSMENT; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SIDE EFFECT; TREATMENT DURATION; TREATMENT RESPONSE; TREATMENT WITHDRAWAL; ANTAGONISTS AND INHIBITORS; CHEMICALLY INDUCED; CLINICAL TRIAL; MIDDLE AGED; MULTICENTER STUDY; OPPORTUNISTIC INFECTION; SEVERITY OF ILLNESS INDEX; TREATMENT OUTCOME;

ADULT; ANTIRHEUMATIC AGENTS; DOUBLE-BLIND METHOD; FEMALE; HUMANS; JANUS KINASE 1; JANUS KINASE INHIBITORS; MALE; MIDDLE AGED; NASOPHARYNGITIS; OPPORTUNISTIC INFECTIONS; PNEUMONIA; PYRIDINES; SEVERITY OF ILLNESS INDEX; SPONDYLITIS, ANKYLOSING; TREATMENT OUTCOME; TRIAZOLES;

EID: 85055083813     PISSN: 01406736     EISSN: 1474547X     Source Type: Journal    
DOI: 10.1016/S0140-6736(18)32463-2     Document Type: Article

References (33)

1. Sieper, J, Poddubnyy, D, Axial spondyloarthritis. Lancet 390 (2017), 73–84.
2. Stolwijk, C, van Tubergen, A, Castillo-Ortiz, JD, Boonen, A, Prevalence of extra-articular manifestations in patients with ankylosing spondylitis: a systematic review and meta-analysis. Ann Rheum Dis 74 (2015), 65–73.
3. Stolwijk, C, van Onna, M, Boonen, A, van Tubergen, A, Global prevalence of spondyloarthritis: a systematic review and meta-regression analysis. Arthritis Care Res 68 (2016), 1320–1331.
4. Tsui, FW, Tsui, HW, Akram, A, Haroon, N, Inman, RD, The genetic basis of ankylosing spondylitis: new insights into disease pathogenesis. Appl Clin Genet 7 (2014), 105–115.
5. Landewe, R, Dougados, M, Mielants, H, van der Tempel, H, van der Heijde, D, Physical function in ankylosing spondylitis is independently determined by both disease activity and radiographic damage of the spine. Ann Rheum Dis 68 (2009), 863–867.
6. Martindale, J, Shukla, R, Goodacre, J, The impact of ankylosing spondylitis/axial spondyloarthritis on work productivity. Best Pract Res Clin Rheumatol 29 (2015), 512–523.
7. van der Heijde, D, Ramiro, S, Landewe, R, et al. 2016 update of the ASAS–EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis 76 (2017), 978–991.
8. Veale, DJ, McGonagle, D, McInnes, IB, et al. The rationale for Janus kinase inhibitors for the treatment of spondyloarthritis. Rheumatology, 2018 published online April 3. DOI:10.1093/rheumatology/key070.
9. Baeten, D, Ostergaard, M, Wei, JC, et al. Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study. Ann Rheum Dis 77 (2018), 1295–1302.
10. Sieper, J, Braun, J, Kay, J, et al. Sarilumab for the treatment of ankylosing spondylitis: results of a phase II, randomised, double-blind, placebo-controlled study (ALIGN). Ann Rheum Dis 74 (2015), 1051–1057.
11. Jethwa, H, Bowness, P, The interleukin (IL)-23/IL-17 axis in ankylosing spondylitis: new advances and potentials for treatment. Clin Exp Immunol 183 (2016), 30–36.
12. Namour, F, Diderichsen, PM, Cox, E, et al. Pharmacokinetics and pharmacokinetic/pharmacodynamic modeling of filgotinib (GLPG0634), a selective JAK1 inhibitor, in support of phase IIb dose selection. Clin Pharmacokinet 54 (2015), 859–874.
13. Haan, C, Rolvering, C, Raulf, F, et al. JAK1 has a dominant role over JAK3 in signal transduction through gammac-containing cytokine receptors. Chem Biol 18 (2011), 314–323.
14. van der Heijde, D, Deodhar, A, Wei, JC, et al. Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study. Ann Rheum Dis 76 (2017), 1340–1347.
15. Westhovens, R, Taylor, PC, Alten, R, et al. Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1). Ann Rheum Dis 76 (2017), 998–1008.
16. Kavanaugh, A, Kremer, J, Ponce, L, et al. Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2). Ann Rheum Dis 76 (2017), 1009–1019.
17. Genovese, M, Westhovens, R, Meuleners, L, et al. Effect of filgotinib, a selective JAK 1 inhibitor, with and without methotrexate in patients with rheumatoid arthritis: patient-reported outcomes. Arthritis Res Ther, 20, 2018, 57.
18. Vermeire, S, Schreiber, S, Petryka, R, et al. Clinical remission in patients with moderate-to-severe Crohn's disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial. Lancet 389 (2017), 266–275.
19. Mease, P, Coates, LC, Helliwell, PS, et al. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo-controlled, phase 2 trial. Lancet, 2018 published online Oct 22. http://dx.doi.org/10.1016/S0140-6736(18)32483-8.
20. van der Linden, S, Valkenburg, HA, Cats, A, Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27 (1984), 361–368.
21. Tanaka, Y, Recent progress and perspective in JAK inhibitors for rheumatoid arthritis: from bench to bedside. J Biochem 158 (2015), 173–179.
22. Scott, IC, Hider, SL, Scott, DL, Thromboembolism with Janus kinase (JAK) inhibitors for rheumatoid arthritis: how real is the risk?. Drug Saf 41 (2018), 645–653.
23. Verden, A, Dimbil, M, Kyle, R, Overstreet, B, Hoffman, KB, Analysis of spontaneous postmarket case reports submitted to the FDA regarding thromboembolic adverse events and JAK inhibitors. Drug Saf 41 (2018), 357–361.
24. Bengtsson, K, Forsblad-d'Elia, H, Lie, E, et al. Are ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis associated with an increased risk of cardiovascular events? A prospective nationwide population-based cohort study. Arthritis Res Ther, 19, 2017, 102.
25. Eriksson, JK, Jacobsson, L, Bengtsson, K, Askling, J, Is ankylosing spondylitis a risk factor for cardiovascular disease, and how do these risks compare with those in rheumatoid arthritis?. Ann Rheum Dis 76 (2017), 364–370.
26. van der Heijde, D, Gensler, L, Deodhar, A, et al. Dual neutralisation of IL-17a and IL-17f with bimekizumab in patients with active ankylosing spondylitis (AS): 12-week results from a phase 2b, randomised, double-blind, placebo-controlled, dose-ranging study [abstract LB0001]. Ann Rheum Dis, 77(suppl 2), 2018, 70.
27. Landewe, R, Braun, J, Deodhar, A, et al. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled phase 3 study. Ann Rheum Dis 73 (2014), 39–47.
28. van der Heijde, D, Kivitz, A, Schiff, MH, et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 54 (2006), 2136–2146.
29. Braun, J, Sieper, J, Aelion, J, et al. Secukinumab improves multiple parameters of disease activity in subjects with active ankylosing spondylitis through 52 weeks of subcutaneous therapy: data from the phase 3 measure 2 study [AB0743]. Ann Rheum Dis, 74(suppl 2), 2015, 1147.
30. Maxwell, LJ, Zochling, J, Boonen, A, et al. TNF-alpha inhibitors for ankylosing spondylitis (review). Cochrane Database Syst Rev, 4, 2015 CD005468.
31. Wanders, AJ, Gorman, JD, Davis, JC, Landewe, RB, van der Heijde, DM, Responsiveness and discriminative capacity of the assessments in ankylosing spondylitis disease-controlling antirheumatic therapy core set and other outcome measures in a trial of etanercept in ankylosing spondylitis. Arthritis Rheum 51 (2004), 1–8.
32. Schwartz, DM, Kanno, Y, Villarino, A, Ward, M, Gadina, M, O'Shea, JJ, JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov 16 (2017), 843–862.
33. Baker, KF, Isaacs, JD, Novel therapies for immune-mediated inflammatory diseases: what can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn's disease and ulcerative colitis?. Ann Rheum Dis 77 (2018), 175–187.