Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials

Gerd R. Burmester; Richard G Wunderink; Ricardo Blanco; Peter Nash; Philippe Goupille; Valderilio F. Azevedo; Carlo Salvarani; Andrea Rubbert-Roth; Elizabeth Lesser; Ralph Lippe; Apinya Lertratanakul; Reva M. Mccaskill; John Liu; Eric M. Ruderman

doi:10.1007/s40744-021-00410-z

Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials

Gerd R. Burmester^*, Richard G Wunderink, Ricardo Blanco, Peter Nash, Philippe Goupille, Valderilio F. Azevedo, Carlo Salvarani, Andrea Rubbert-Roth, Elizabeth Lesser, Ralph Lippe, Apinya Lertratanakul, Reva M. Mccaskill, John Liu, Eric M. Ruderman

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	521-539
Number of pages	19
Journal	Rheumatology and Therapy
Volume	9
Issue number	2
DOIs	https://doi.org/10.1007/s40744-021-00410-z
State	Published - Apr 2022

Funding

AbbVie and the authors thank the patients, study sites, and investigators who participated in these clinical trials. AbbVie Inc. (North Chicago, IL, USA) funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. AbbVie Inc. (North Chicago, IL, USA) funded the journal’s Rapid Service Fee. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. AL, RMM, and JL were involved in the acquisition of data. All authors were involved in the analysis and interpretation of the data, drafting the article, and revising it for critically important intellectual content, and approving the final version of manuscript. AbbVie and the authors thank Hannah Palac, Jayesh Patel, and Saeed Motabar, employees of AbbVie Inc., and Bosny J Pierre-Louis, a former employee of AbbVie Inc., for contributions to statistical analyses, and Julia Zolotarjova, MSc, MWC, an employee of AbbVie Inc., for medical writing support. The main findings of this study were presented in an abstract that was accepted for publication by the European Congress of Rheumatology 2021 in a supplement to the Ann Rheum Dis. GR Burmester has received consulting fees and speaker honoraria from AbbVie, Eli Lilly, Galapagos, Gilead, and Pfizer. K Winthrop has received consulting fees and/or research grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Galapagos, GlaxoSmithKline, Gilead, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB. R Blanco has received grants/research support from AbbVie, MSD, and Roche, and consulting fees/participation in company-sponsored speaker’s bureau from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and Roche. P Nash has received funding for clinical trials, research grants, and honoraria for advice and lectures from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead/Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Samsung, Sanofi, and UCB. P Goupille has received research grants, consulting fees, or speaker honoraria from AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Galapagos, Eli Lilly, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, and UCB. VF Azevedo has received funding for clinical trials, research grants, and honoraria for lectures and advice from AbbVie, Amgen, Bristol-Meyers Squibb, Celltrion, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB. C Salvarani has received consulting fees and research grants from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Roche, and Sanofi-Genzyme. A Rubbert-Roth has received honoraria for lectures and consulting fees from AbbVie, Amgen, Bristol Myers-Squibb, Chugai, Eli Lilly, Gilead, Janssen, Novartis, Roche, and Sanofi. EM Ruderman has received consulting fees from AbbVie, Amgen, Bristol Myers-Squibb, Eli Lilly, Gilead, Janssen, Novartis, and Pfizer. E Lesser, R Lippe, RM Mccaskill , and J Liu are employees of AbbVie Inc. and may hold stock or options. A Lertratanakul is a former employee of AbbVie Inc. and may hold stock or options. The trials were conducted according to the International Conference on Harmonization guidelines, the Declaration of Helsinki principles, and applicable local country regulations. All study-related documents were approved by independent ethics committees and institutional review boards at each site (Supplemental Material: Table S2). All patients gave written informed consent. AbbVie Inc. is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and Clinical Study Reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. This clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html. GR Burmester has received consulting fees and speaker honoraria from AbbVie, Eli Lilly, Galapagos, Gilead, and Pfizer. K Winthrop has received consulting fees and/or research grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Galapagos, GlaxoSmithKline, Gilead, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB. R Blanco has received grants/research support from AbbVie, MSD, and Roche, and consulting fees/participation in company-sponsored speaker’s bureau from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and Roche. P Nash has received funding for clinical trials, research grants, and honoraria for advice and lectures from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead/Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Samsung, Sanofi, and UCB. P Goupille has received research grants, consulting fees, or speaker honoraria from AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Galapagos, Eli Lilly, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, and UCB. VF Azevedo has received funding for clinical trials, research grants, and honoraria for lectures and advice from AbbVie, Amgen, Bristol-Meyers Squibb, Celltrion, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB. C Salvarani has received consulting fees and research grants from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Roche, and Sanofi-Genzyme. A Rubbert-Roth has received honoraria for lectures and consulting fees from AbbVie, Amgen, Bristol Myers-Squibb, Chugai, Eli Lilly, Gilead, Janssen, Novartis, Roche, and Sanofi. EM Ruderman has received consulting fees from AbbVie, Amgen, Bristol Myers-Squibb, Eli Lilly, Gilead, Janssen, Novartis, and Pfizer. E Lesser, R Lippe, RM Mccaskill, and J Liu are employees of AbbVie Inc. and may hold stock or options. A Lertratanakul is a former employee of AbbVie Inc. and may hold stock or options.

Keywords

Adalimumab
JAK inhibitor
Psoriatic arthritis
SELECT-PsA 1
SELECT-PsA 2
Safety
Upadacitinib

ASJC Scopus subject areas

Rheumatology
Immunology and Allergy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s40744-021-00410-z

Cite this

Burmester, G. R., Wunderink, R. G., Blanco, R., Nash, P., Goupille, P., Azevedo, V. F., Salvarani, C., Rubbert-Roth, A., Lesser, E., Lippe, R., Lertratanakul, A., Mccaskill, R. M., Liu, J., & Ruderman, E. M. (2022). Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials. Rheumatology and Therapy, 9(2), 521-539. https://doi.org/10.1007/s40744-021-00410-z

@article{d8faa3db3d174e33845eb0b7084d46c1,

title = "Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials",

abstract = "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.",

keywords = "Adalimumab, JAK inhibitor, Psoriatic arthritis, SELECT-PsA 1, SELECT-PsA 2, Safety, Upadacitinib",

author = "Burmester, {Gerd R.} and Wunderink, {Richard G} and Ricardo Blanco and Peter Nash and Philippe Goupille and Azevedo, {Valderilio F.} and Carlo Salvarani and Andrea Rubbert-Roth and Elizabeth Lesser and Ralph Lippe and Apinya Lertratanakul and Mccaskill, {Reva M.} and John Liu and Ruderman, {Eric M.}",

note = "Funding Information: AbbVie and the authors thank the patients, study sites, and investigators who participated in these clinical trials. AbbVie Inc. (North Chicago, IL, USA) funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. AbbVie Inc. (North Chicago, IL, USA) funded the journal{\textquoteright}s Rapid Service Fee. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. AL, RMM, and JL were involved in the acquisition of data. All authors were involved in the analysis and interpretation of the data, drafting the article, and revising it for critically important intellectual content, and approving the final version of manuscript. AbbVie and the authors thank Hannah Palac, Jayesh Patel, and Saeed Motabar, employees of AbbVie Inc., and Bosny J Pierre-Louis, a former employee of AbbVie Inc., for contributions to statistical analyses, and Julia Zolotarjova, MSc, MWC, an employee of AbbVie Inc., for medical writing support. The main findings of this study were presented in an abstract that was accepted for publication by the European Congress of Rheumatology 2021 in a supplement to the Ann Rheum Dis. GR Burmester has received consulting fees and speaker honoraria from AbbVie, Eli Lilly, Galapagos, Gilead, and Pfizer. K Winthrop has received consulting fees and/or research grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Galapagos, GlaxoSmithKline, Gilead, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB. R Blanco has received grants/research support from AbbVie, MSD, and Roche, and consulting fees/participation in company-sponsored speaker{\textquoteright}s bureau from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and Roche. P Nash has received funding for clinical trials, research grants, and honoraria for advice and lectures from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead/Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Samsung, Sanofi, and UCB. P Goupille has received research grants, consulting fees, or speaker honoraria from AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Galapagos, Eli Lilly, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, and UCB. VF Azevedo has received funding for clinical trials, research grants, and honoraria for lectures and advice from AbbVie, Amgen, Bristol-Meyers Squibb, Celltrion, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB. C Salvarani has received consulting fees and research grants from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Roche, and Sanofi-Genzyme. A Rubbert-Roth has received honoraria for lectures and consulting fees from AbbVie, Amgen, Bristol Myers-Squibb, Chugai, Eli Lilly, Gilead, Janssen, Novartis, Roche, and Sanofi. EM Ruderman has received consulting fees from AbbVie, Amgen, Bristol Myers-Squibb, Eli Lilly, Gilead, Janssen, Novartis, and Pfizer. E Lesser, R Lippe, RM Mccaskill , and J Liu are employees of AbbVie Inc. and may hold stock or options. A Lertratanakul is a former employee of AbbVie Inc. and may hold stock or options. The trials were conducted according to the International Conference on Harmonization guidelines, the Declaration of Helsinki principles, and applicable local country regulations. All study-related documents were approved by independent ethics committees and institutional review boards at each site (Supplemental Material: Table S2). All patients gave written informed consent. AbbVie Inc. is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and Clinical Study Reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. This clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html. Funding Information: GR Burmester has received consulting fees and speaker honoraria from AbbVie, Eli Lilly, Galapagos, Gilead, and Pfizer. K Winthrop has received consulting fees and/or research grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Galapagos, GlaxoSmithKline, Gilead, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB. R Blanco has received grants/research support from AbbVie, MSD, and Roche, and consulting fees/participation in company-sponsored speaker{\textquoteright}s bureau from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and Roche. P Nash has received funding for clinical trials, research grants, and honoraria for advice and lectures from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead/Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Samsung, Sanofi, and UCB. P Goupille has received research grants, consulting fees, or speaker honoraria from AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Galapagos, Eli Lilly, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, and UCB. VF Azevedo has received funding for clinical trials, research grants, and honoraria for lectures and advice from AbbVie, Amgen, Bristol-Meyers Squibb, Celltrion, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB. C Salvarani has received consulting fees and research grants from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Roche, and Sanofi-Genzyme. A Rubbert-Roth has received honoraria for lectures and consulting fees from AbbVie, Amgen, Bristol Myers-Squibb, Chugai, Eli Lilly, Gilead, Janssen, Novartis, Roche, and Sanofi. EM Ruderman has received consulting fees from AbbVie, Amgen, Bristol Myers-Squibb, Eli Lilly, Gilead, Janssen, Novartis, and Pfizer. E Lesser, R Lippe, RM Mccaskill, and J Liu are employees of AbbVie Inc. and may hold stock or options. A Lertratanakul is a former employee of AbbVie Inc. and may hold stock or options. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2022",

month = apr,

doi = "10.1007/s40744-021-00410-z",

language = "English (US)",

volume = "9",

pages = "521--539",

journal = "Rheumatology and Therapy",

issn = "2198-6576",

publisher = "Adis International Ltd",

number = "2",

}

Burmester, GR, Wunderink, RG, Blanco, R, Nash, P, Goupille, P, Azevedo, VF, Salvarani, C, Rubbert-Roth, A, Lesser, E, Lippe, R, Lertratanakul, A, Mccaskill, RM, Liu, J & Ruderman, EM 2022, 'Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials', Rheumatology and Therapy, vol. 9, no. 2, pp. 521-539. https://doi.org/10.1007/s40744-021-00410-z

TY - JOUR

T1 - Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis

T2 - An Integrated Analysis of Two Pivotal Phase 3 Trials

AU - Burmester, Gerd R.

AU - Wunderink, Richard G

AU - Blanco, Ricardo

AU - Nash, Peter

AU - Goupille, Philippe

AU - Azevedo, Valderilio F.

AU - Salvarani, Carlo

AU - Rubbert-Roth, Andrea

AU - Lesser, Elizabeth

AU - Lippe, Ralph

AU - Lertratanakul, Apinya

AU - Mccaskill, Reva M.

AU - Liu, John

AU - Ruderman, Eric M.

N1 - Funding Information: AbbVie and the authors thank the patients, study sites, and investigators who participated in these clinical trials. AbbVie Inc. (North Chicago, IL, USA) funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. AbbVie Inc. (North Chicago, IL, USA) funded the journal’s Rapid Service Fee. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. AL, RMM, and JL were involved in the acquisition of data. All authors were involved in the analysis and interpretation of the data, drafting the article, and revising it for critically important intellectual content, and approving the final version of manuscript. AbbVie and the authors thank Hannah Palac, Jayesh Patel, and Saeed Motabar, employees of AbbVie Inc., and Bosny J Pierre-Louis, a former employee of AbbVie Inc., for contributions to statistical analyses, and Julia Zolotarjova, MSc, MWC, an employee of AbbVie Inc., for medical writing support. The main findings of this study were presented in an abstract that was accepted for publication by the European Congress of Rheumatology 2021 in a supplement to the Ann Rheum Dis. GR Burmester has received consulting fees and speaker honoraria from AbbVie, Eli Lilly, Galapagos, Gilead, and Pfizer. K Winthrop has received consulting fees and/or research grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Galapagos, GlaxoSmithKline, Gilead, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB. R Blanco has received grants/research support from AbbVie, MSD, and Roche, and consulting fees/participation in company-sponsored speaker’s bureau from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and Roche. P Nash has received funding for clinical trials, research grants, and honoraria for advice and lectures from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead/Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Samsung, Sanofi, and UCB. P Goupille has received research grants, consulting fees, or speaker honoraria from AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Galapagos, Eli Lilly, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, and UCB. VF Azevedo has received funding for clinical trials, research grants, and honoraria for lectures and advice from AbbVie, Amgen, Bristol-Meyers Squibb, Celltrion, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB. C Salvarani has received consulting fees and research grants from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Roche, and Sanofi-Genzyme. A Rubbert-Roth has received honoraria for lectures and consulting fees from AbbVie, Amgen, Bristol Myers-Squibb, Chugai, Eli Lilly, Gilead, Janssen, Novartis, Roche, and Sanofi. EM Ruderman has received consulting fees from AbbVie, Amgen, Bristol Myers-Squibb, Eli Lilly, Gilead, Janssen, Novartis, and Pfizer. E Lesser, R Lippe, RM Mccaskill , and J Liu are employees of AbbVie Inc. and may hold stock or options. A Lertratanakul is a former employee of AbbVie Inc. and may hold stock or options. The trials were conducted according to the International Conference on Harmonization guidelines, the Declaration of Helsinki principles, and applicable local country regulations. All study-related documents were approved by independent ethics committees and institutional review boards at each site (Supplemental Material: Table S2). All patients gave written informed consent. AbbVie Inc. is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and Clinical Study Reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. This clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html. Funding Information: GR Burmester has received consulting fees and speaker honoraria from AbbVie, Eli Lilly, Galapagos, Gilead, and Pfizer. K Winthrop has received consulting fees and/or research grants from AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Galapagos, GlaxoSmithKline, Gilead, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB. R Blanco has received grants/research support from AbbVie, MSD, and Roche, and consulting fees/participation in company-sponsored speaker’s bureau from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and Roche. P Nash has received funding for clinical trials, research grants, and honoraria for advice and lectures from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead/Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Samsung, Sanofi, and UCB. P Goupille has received research grants, consulting fees, or speaker honoraria from AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Galapagos, Eli Lilly, Janssen, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi, and UCB. VF Azevedo has received funding for clinical trials, research grants, and honoraria for lectures and advice from AbbVie, Amgen, Bristol-Meyers Squibb, Celltrion, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB. C Salvarani has received consulting fees and research grants from AbbVie, Amgen, Eli Lilly, Novartis, Pfizer, Roche, and Sanofi-Genzyme. A Rubbert-Roth has received honoraria for lectures and consulting fees from AbbVie, Amgen, Bristol Myers-Squibb, Chugai, Eli Lilly, Gilead, Janssen, Novartis, Roche, and Sanofi. EM Ruderman has received consulting fees from AbbVie, Amgen, Bristol Myers-Squibb, Eli Lilly, Gilead, Janssen, Novartis, and Pfizer. E Lesser, R Lippe, RM Mccaskill, and J Liu are employees of AbbVie Inc. and may hold stock or options. A Lertratanakul is a former employee of AbbVie Inc. and may hold stock or options. Publisher Copyright: © 2021, The Author(s).

PY - 2022/4

Y1 - 2022/4

N2 - 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.

AB - 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.

KW - Adalimumab

KW - JAK inhibitor

KW - Psoriatic arthritis

KW - SELECT-PsA 1

KW - SELECT-PsA 2

KW - Safety

KW - Upadacitinib

UR - http://www.scopus.com/inward/record.url?scp=85122068889&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85122068889&partnerID=8YFLogxK

U2 - 10.1007/s40744-021-00410-z

DO - 10.1007/s40744-021-00410-z

M3 - Article

C2 - 34970731

AN - SCOPUS:85122068889

SN - 2198-6576

VL - 9

SP - 521

EP - 539

JO - Rheumatology and Therapy

JF - Rheumatology and Therapy

IS - 2

ER -

Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials

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