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Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials
INTRODUCTION: This integrated analysis describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, at 15 and 30 mg once daily for up to 3 years of exposure in patients with active psoriatic arthritis (PsA) who had a prior inadequate response or intolerance to ≥ 1 non-biologic or bi...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Healthcare
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8717827/ https://www.ncbi.nlm.nih.gov/pubmed/34970731 http://dx.doi.org/10.1007/s40744-021-00410-z |
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author | Burmester, Gerd R. Winthrop, Kevin Blanco, Ricardo Nash, Peter Goupille, Philippe Azevedo, Valderilio F. Salvarani, Carlo Rubbert-Roth, Andrea Lesser, Elizabeth Lippe, Ralph Lertratanakul, Apinya Mccaskill, Reva M. Liu, John Ruderman, Eric M. |
author_facet | Burmester, Gerd R. Winthrop, Kevin Blanco, Ricardo Nash, Peter Goupille, Philippe Azevedo, Valderilio F. Salvarani, Carlo Rubbert-Roth, Andrea Lesser, Elizabeth Lippe, Ralph Lertratanakul, Apinya Mccaskill, Reva M. Liu, John Ruderman, Eric M. |
author_sort | Burmester, Gerd R. |
collection | PubMed |
description | INTRODUCTION: This integrated analysis describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, at 15 and 30 mg once daily for up to 3 years of exposure in patients with active psoriatic arthritis (PsA) who had a prior inadequate response or intolerance to ≥ 1 non-biologic or biologic disease-modifying antirheumatic drug. METHODS: Safety data were pooled and analyzed from two randomized, placebo-controlled phase 3 trials. Both trials evaluated upadacitinib 15 mg and 30 mg once daily, and one trial also evaluated adalimumab 40 mg every other week. Treatment-emergent adverse events (TEAEs) and laboratory data were summarized for four groups: pooled placebo, pooled upadacitinib 15 mg, pooled upadacitinib 30 mg, and adalimumab. TEAEs were reported as exposure-adjusted event rates (events per 100 patient-years [E/100 PY]) up to a data cut-off of June 29, 2020. RESULTS: A total of 2257 patients received ≥ 1 dose of upadacitinib 15 mg (N = 907) or 30 mg (N = 921) for 2504.6 PY of exposure or adalimumab (N = 429) for 549.7 PY of exposure. Upper respiratory tract infection, nasopharyngitis, and increased creatine phosphokinase (CPK) were the most common TEAEs with upadacitinib. Rates of malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs), and deaths were similar across treatment groups. Rates of herpes zoster (HZ) and opportunistic infections (OI; excluding tuberculosis, HZ, and oral candidiasis) were higher with upadacitinib versus adalimumab. Serious infection, anemia, and CPK elevations were most frequent with upadacitinib 30 mg. Potentially clinically significant laboratory abnormalities were uncommon. CONCLUSIONS: Upadacitinib 15 mg and adalimumab had similar safety profiles with the exception of HZ and OIs, consistent with what was observed in rheumatoid arthritis. Rates of malignancies, MACEs, VTEs, and deaths were comparable among patients receiving upadacitinib and adalimumab. No new safety risks emerged with longer-term exposure to upadacitinib. TRIAL REGISTRATION NUMBERS: SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40744-021-00410-z. |
format | Online Article Text |
id | pubmed-8717827 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Healthcare |
record_format | MEDLINE/PubMed |
spelling | pubmed-87178272022-01-03 Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials Burmester, Gerd R. Winthrop, Kevin Blanco, Ricardo Nash, Peter Goupille, Philippe Azevedo, Valderilio F. Salvarani, Carlo Rubbert-Roth, Andrea Lesser, Elizabeth Lippe, Ralph Lertratanakul, Apinya Mccaskill, Reva M. Liu, John Ruderman, Eric M. Rheumatol Ther Original Research INTRODUCTION: This integrated analysis describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, at 15 and 30 mg once daily for up to 3 years of exposure in patients with active psoriatic arthritis (PsA) who had a prior inadequate response or intolerance to ≥ 1 non-biologic or biologic disease-modifying antirheumatic drug. METHODS: Safety data were pooled and analyzed from two randomized, placebo-controlled phase 3 trials. Both trials evaluated upadacitinib 15 mg and 30 mg once daily, and one trial also evaluated adalimumab 40 mg every other week. Treatment-emergent adverse events (TEAEs) and laboratory data were summarized for four groups: pooled placebo, pooled upadacitinib 15 mg, pooled upadacitinib 30 mg, and adalimumab. TEAEs were reported as exposure-adjusted event rates (events per 100 patient-years [E/100 PY]) up to a data cut-off of June 29, 2020. RESULTS: A total of 2257 patients received ≥ 1 dose of upadacitinib 15 mg (N = 907) or 30 mg (N = 921) for 2504.6 PY of exposure or adalimumab (N = 429) for 549.7 PY of exposure. Upper respiratory tract infection, nasopharyngitis, and increased creatine phosphokinase (CPK) were the most common TEAEs with upadacitinib. Rates of malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs), and deaths were similar across treatment groups. Rates of herpes zoster (HZ) and opportunistic infections (OI; excluding tuberculosis, HZ, and oral candidiasis) were higher with upadacitinib versus adalimumab. Serious infection, anemia, and CPK elevations were most frequent with upadacitinib 30 mg. Potentially clinically significant laboratory abnormalities were uncommon. CONCLUSIONS: Upadacitinib 15 mg and adalimumab had similar safety profiles with the exception of HZ and OIs, consistent with what was observed in rheumatoid arthritis. Rates of malignancies, MACEs, VTEs, and deaths were comparable among patients receiving upadacitinib and adalimumab. No new safety risks emerged with longer-term exposure to upadacitinib. TRIAL REGISTRATION NUMBERS: SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40744-021-00410-z. Springer Healthcare 2021-12-30 /pmc/articles/PMC8717827/ /pubmed/34970731 http://dx.doi.org/10.1007/s40744-021-00410-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Original Research Burmester, Gerd R. Winthrop, Kevin Blanco, Ricardo Nash, Peter Goupille, Philippe Azevedo, Valderilio F. Salvarani, Carlo Rubbert-Roth, Andrea Lesser, Elizabeth Lippe, Ralph Lertratanakul, Apinya Mccaskill, Reva M. Liu, John Ruderman, Eric M. Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials |
title | Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials |
title_full | Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials |
title_fullStr | Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials |
title_full_unstemmed | Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials |
title_short | Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials |
title_sort | safety profile of upadacitinib up to 3 years in psoriatic arthritis: an integrated analysis of two pivotal phase 3 trials |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8717827/ https://www.ncbi.nlm.nih.gov/pubmed/34970731 http://dx.doi.org/10.1007/s40744-021-00410-z |
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