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Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial.
Lancet. 2019 12 07; 394(10214):2108-2117.Lct

Abstract

BACKGROUND

The JAK pathway is a potential therapeutic target in ankylosing spondylitis. This study assessed the efficacy and safety of upadacitinib, a selective JAK1 inhibitor, in patients with ankylosing spondylitis.

METHODS

This multicentre, randomised, double-blind, placebo-controlled, two-period, parallel-group, phase 2/3 study, SELECT-AXIS 1, enrolled adults in 62 sites in 20 countries. Eligible patients had active ankylosing spondylitis, fulfilled modified New York criteria, were previously untreated with biological disease-modifying antirheumatic drugs, and had inadequate response to at least two or intolerance or contraindication to non-steroidal anti-inflammatory drugs. Patients were randomly assigned 1:1 using interactive response technology to take oral upadacitinib 15 mg once daily or oral placebo for the 14-week period 1; only period 1 data are reported here. The primary endpoint was the composite outcome measure of the Assessment of SpondyloArthritis international Society 40 response at week 14. Analyses were done in the full analysis set of patients who were randomly assigned and received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03178487.

FINDINGS

Between Nov 30, 2017, and Oct 15, 2018, 187 patients were randomly assigned to upadacitinib 15 mg (93 patients) or to placebo (94 patients), and 178 (95%) patients (89 in the upadacitinib group and 89 in the placebo group) completed period 1 on study drug (by the completion date of Jan 21, 2019). Significantly more patients had an Assessment of SpondyloArthritis international Society 40 response in the upadacitinib group versus in the placebo group at week 14 (48 [52%] of 93 patients vs 24 [26%] of 94 patients; p=0·0003; treatment difference 26% [95% CI 13-40]). Adverse events were reported in 58 (62%) of 93 patients in the upadacitinib group versus 52 (55%) of 94 in the placebo group. The most common adverse event in the upadacitinib group was increased creatine phosphokinase (eight [9%] of 93 patients in the upadacitinib group vs two [2%] of 94 patients with placebo). No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported; one serious adverse event was reported in each group.

INTERPRETATION

Upadacitinib 15 mg was efficacious and well tolerated in patients with active ankylosing spondylitis who had an inadequate response or contraindication to non-steroidal anti-inflammatory drugs. These data support the further investigation of upadacitinib for the treatment of axial spondyloarthritis.

FUNDING

AbbVie.

Authors+Show Affiliations

Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands. Electronic address: mail@dvanderheijde.nl.Immunology Clinical Development and Data and Statistical Sciences, AbbVie, North Chicago, IL, USA.Immunology Clinical Development and Data and Statistical Sciences, AbbVie, North Chicago, IL, USA.Division of Arthritis and Rheumatic Diseases, Oregon Health and Science University, Portland, OR, USA.Department of Internal Medicine and Pediatrics, Ghent University, VIB Center for Inflammation Research, Ghent, Belgium.Department of Medicine, University of Alberta, Edmonton, AB, Canada.Division of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan.Hamburger Rheuma-Forschungszentrum, Hamburg, Germany.Immunology Clinical Development and Data and Statistical Sciences, AbbVie, North Chicago, IL, USA.Immunology Clinical Development and Data and Statistical Sciences, AbbVie, North Chicago, IL, USA.Immunology Clinical Development and Data and Statistical Sciences, AbbVie, North Chicago, IL, USA.Department of Gastroenterology, Infectious Diseases, and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany.

Pub Type(s)

Clinical Trial, Phase II
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31732180

Citation

van der Heijde, Désirée, et al. "Efficacy and Safety of Upadacitinib in Patients With Active Ankylosing Spondylitis (SELECT-AXIS 1): a Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 2/3 Trial." Lancet (London, England), vol. 394, no. 10214, 2019, pp. 2108-2117.
van der Heijde D, Song IH, Pangan AL, et al. Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial. Lancet. 2019;394(10214):2108-2117.
van der Heijde, D., Song, I. H., Pangan, A. L., Deodhar, A., van den Bosch, F., Maksymowych, W. P., Kim, T. H., Kishimoto, M., Everding, A., Sui, Y., Wang, X., Chu, A. D., & Sieper, J. (2019). Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial. Lancet (London, England), 394(10214), 2108-2117. https://doi.org/10.1016/S0140-6736(19)32534-6
van der Heijde D, et al. Efficacy and Safety of Upadacitinib in Patients With Active Ankylosing Spondylitis (SELECT-AXIS 1): a Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 2/3 Trial. Lancet. 2019 12 7;394(10214):2108-2117. PubMed PMID: 31732180.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial. AU - van der Heijde,Désirée, AU - Song,In-Ho, AU - Pangan,Aileen L, AU - Deodhar,Atul, AU - van den Bosch,Filip, AU - Maksymowych,Walter P, AU - Kim,Tae-Hwan, AU - Kishimoto,Mitsumasa, AU - Everding,Andrea, AU - Sui,Yunxia, AU - Wang,Xin, AU - Chu,Alvina D, AU - Sieper,Joachim, Y1 - 2019/11/12/ PY - 2019/09/24/received PY - 2019/10/10/revised PY - 2019/10/15/accepted PY - 2019/11/17/pubmed PY - 2020/1/7/medline PY - 2019/11/17/entrez SP - 2108 EP - 2117 JF - Lancet (London, England) JO - Lancet VL - 394 IS - 10214 N2 - BACKGROUND: The JAK pathway is a potential therapeutic target in ankylosing spondylitis. This study assessed the efficacy and safety of upadacitinib, a selective JAK1 inhibitor, in patients with ankylosing spondylitis. METHODS: This multicentre, randomised, double-blind, placebo-controlled, two-period, parallel-group, phase 2/3 study, SELECT-AXIS 1, enrolled adults in 62 sites in 20 countries. Eligible patients had active ankylosing spondylitis, fulfilled modified New York criteria, were previously untreated with biological disease-modifying antirheumatic drugs, and had inadequate response to at least two or intolerance or contraindication to non-steroidal anti-inflammatory drugs. Patients were randomly assigned 1:1 using interactive response technology to take oral upadacitinib 15 mg once daily or oral placebo for the 14-week period 1; only period 1 data are reported here. The primary endpoint was the composite outcome measure of the Assessment of SpondyloArthritis international Society 40 response at week 14. Analyses were done in the full analysis set of patients who were randomly assigned and received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03178487. FINDINGS: Between Nov 30, 2017, and Oct 15, 2018, 187 patients were randomly assigned to upadacitinib 15 mg (93 patients) or to placebo (94 patients), and 178 (95%) patients (89 in the upadacitinib group and 89 in the placebo group) completed period 1 on study drug (by the completion date of Jan 21, 2019). Significantly more patients had an Assessment of SpondyloArthritis international Society 40 response in the upadacitinib group versus in the placebo group at week 14 (48 [52%] of 93 patients vs 24 [26%] of 94 patients; p=0·0003; treatment difference 26% [95% CI 13-40]). Adverse events were reported in 58 (62%) of 93 patients in the upadacitinib group versus 52 (55%) of 94 in the placebo group. The most common adverse event in the upadacitinib group was increased creatine phosphokinase (eight [9%] of 93 patients in the upadacitinib group vs two [2%] of 94 patients with placebo). No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported; one serious adverse event was reported in each group. INTERPRETATION: Upadacitinib 15 mg was efficacious and well tolerated in patients with active ankylosing spondylitis who had an inadequate response or contraindication to non-steroidal anti-inflammatory drugs. These data support the further investigation of upadacitinib for the treatment of axial spondyloarthritis. FUNDING: AbbVie. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/31732180/Efficacy_and_safety_of_upadacitinib_in_patients_with_active_ankylosing_spondylitis__SELECT_AXIS_1_:_a_multicentre_randomised_double_blind_placebo_controlled_phase_2/3_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(19)32534-6 DB - PRIME DP - Unbound Medicine ER -