Tofacitinib for the treatment of ankylosing spondylitis : a phase III, randomised, double-blind, placebo-controlled study
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ..
OBJECTIVE: To assess the efficacy/safety of tofacitinib in adult patients with active ankylosing spondylitis (AS).
METHODS: This phase III, randomised, double-blind, placebo-controlled study enrolled patients aged ≥18 years diagnosed with active AS, meeting the modified New York criteria, with centrally read radiographs, and an inadequate response or intolerance to ≥2 non-steroidal anti-inflammatory drugs. Patients were randomised 1:1 to receive tofacitinib 5 mg two times per day or placebo for 16 weeks. After week 16, all patients received open-label tofacitinib until week 48. The primary and key secondary endpoints were Assessment of SpondyloArthritis international Society ≥20% improvement (ASAS20) and ≥40% improvement (ASAS40) responses, respectively, at week 16. Safety was assessed throughout.
RESULTS: 269 patients were randomised and treated: tofacitinib, n=133; placebo, n=136. At week 16, the ASAS20 response rate was significantly (p<0.0001) greater with tofacitinib (56.4%, 75 of 133) versus placebo (29.4%, 40 of 136), and the ASAS40 response rate was significantly (p<0.0001) greater with tofacitinib (40.6%, 54 of 133) versus placebo (12.5%, 17 of 136). Up to week 16, with tofacitinib and placebo, respectively, 73 of 133 (54.9%) and 70 of 136 (51.5%) patients had adverse events; 2 of 133 (1.5%) and 1 of 136 (0.7%) had serious adverse events. Up to week 48, with tofacitinib, 3 of 133 (2.3%) patients had adjudicated hepatic events, 3 of 133 (2.3%) had non-serious herpes zoster, and 1 of 133 (0.8%) had a serious infection; with placebo→tofacitinib, 2 (1.5%) patients had non-serious herpes zoster. There were no deaths, malignancies, major adverse cardiovascular events, thromboembolic events or opportunistic infections.
CONCLUSIONS: In adults with active AS, tofacitinib demonstrated significantly greater efficacy versus placebo. No new potential safety risks were identified.
TRIAL REGISTRATION NUMBER: NCT03502616.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:80 |
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| Enthalten in: |
Annals of the rheumatic diseases - 80(2021), 8 vom: 26. Aug., Seite 1004-1013 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Deodhar, Atul [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.06.2022 Date Revised 05.07.2022 published: Print-Electronic ClinicalTrials.gov: NCT03502616 Citation Status MEDLINE |
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| doi: |
10.1136/annrheumdis-2020-219601 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM324602626 |
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| 100 | 1 | |a Deodhar, Atul |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Tofacitinib for the treatment of ankylosing spondylitis |b a phase III, randomised, double-blind, placebo-controlled study |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 27.06.2022 | ||
| 500 | |a Date Revised 05.07.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03502616 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a OBJECTIVE: To assess the efficacy/safety of tofacitinib in adult patients with active ankylosing spondylitis (AS) | ||
| 520 | |a METHODS: This phase III, randomised, double-blind, placebo-controlled study enrolled patients aged ≥18 years diagnosed with active AS, meeting the modified New York criteria, with centrally read radiographs, and an inadequate response or intolerance to ≥2 non-steroidal anti-inflammatory drugs. Patients were randomised 1:1 to receive tofacitinib 5 mg two times per day or placebo for 16 weeks. After week 16, all patients received open-label tofacitinib until week 48. The primary and key secondary endpoints were Assessment of SpondyloArthritis international Society ≥20% improvement (ASAS20) and ≥40% improvement (ASAS40) responses, respectively, at week 16. Safety was assessed throughout | ||
| 520 | |a RESULTS: 269 patients were randomised and treated: tofacitinib, n=133; placebo, n=136. At week 16, the ASAS20 response rate was significantly (p<0.0001) greater with tofacitinib (56.4%, 75 of 133) versus placebo (29.4%, 40 of 136), and the ASAS40 response rate was significantly (p<0.0001) greater with tofacitinib (40.6%, 54 of 133) versus placebo (12.5%, 17 of 136). Up to week 16, with tofacitinib and placebo, respectively, 73 of 133 (54.9%) and 70 of 136 (51.5%) patients had adverse events; 2 of 133 (1.5%) and 1 of 136 (0.7%) had serious adverse events. Up to week 48, with tofacitinib, 3 of 133 (2.3%) patients had adjudicated hepatic events, 3 of 133 (2.3%) had non-serious herpes zoster, and 1 of 133 (0.8%) had a serious infection; with placebo→tofacitinib, 2 (1.5%) patients had non-serious herpes zoster. There were no deaths, malignancies, major adverse cardiovascular events, thromboembolic events or opportunistic infections | ||
| 520 | |a CONCLUSIONS: In adults with active AS, tofacitinib demonstrated significantly greater efficacy versus placebo. No new potential safety risks were identified | ||
| 520 | |a TRIAL REGISTRATION NUMBER: NCT03502616 | ||
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ankylosing | |
| 650 | 4 | |a antirheumatic agents | |
| 650 | 4 | |a spondylitis | |
| 650 | 4 | |a therapeutics | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a Antirheumatic Agents |2 NLM | |
| 650 | 7 | |a Piperidines |2 NLM | |
| 650 | 7 | |a Pyrimidines |2 NLM | |
| 650 | 7 | |a tofacitinib |2 NLM | |
| 650 | 7 | |a 87LA6FU830 |2 NLM | |
| 700 | 1 | |a Sliwinska-Stanczyk, Paula |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Huji |e verfasserin |4 aut | |
| 700 | 1 | |a Baraliakos, Xenofon |e verfasserin |4 aut | |
| 700 | 1 | |a Gensler, Lianne S |e verfasserin |4 aut | |
| 700 | 1 | |a Fleishaker, Dona |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lisy |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Joseph |e verfasserin |4 aut | |
| 700 | 1 | |a Menon, Sujatha |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Cunshan |e verfasserin |4 aut | |
| 700 | 1 | |a Dina, Oluwaseyi |e verfasserin |4 aut | |
| 700 | 1 | |a Fallon, Lara |e verfasserin |4 aut | |
| 700 | 1 | |a Kanik, Keith S |e verfasserin |4 aut | |
| 700 | 1 | |a van der Heijde, Désirée |e verfasserin |4 aut | |
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