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Benefit–Risk Analysis of Upadacitinib Compared with Adalimumab in the Treatment of Patients with Moderate-to-Severe Rheumatoid Arthritis

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease requiring long-term treatment. Upadacitinib (UPA), a Janus kinase (JAK) inhibitor, is a new treatment for RA. The benefit–risk profile of a medication is best understood by evaluating the number needed to treat (NNT) and the num...

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Autores principales: Conaghan, Philip, Cohen, Stanley, Burmester, Gerd, Mysler, Eduardo, Nash, Peter, Tanaka, Yoshiya, Rigby, William, Patel, Jayeshkumar, Shaw, Tim, Betts, Keith A., Patel, Pankaj, Liu, Jianzhong, Sun, Rochelle, Fleischmann, Roy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814262/
https://www.ncbi.nlm.nih.gov/pubmed/34816388
http://dx.doi.org/10.1007/s40744-021-00399-5
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author Conaghan, Philip
Cohen, Stanley
Burmester, Gerd
Mysler, Eduardo
Nash, Peter
Tanaka, Yoshiya
Rigby, William
Patel, Jayeshkumar
Shaw, Tim
Betts, Keith A.
Patel, Pankaj
Liu, Jianzhong
Sun, Rochelle
Fleischmann, Roy
author_facet Conaghan, Philip
Cohen, Stanley
Burmester, Gerd
Mysler, Eduardo
Nash, Peter
Tanaka, Yoshiya
Rigby, William
Patel, Jayeshkumar
Shaw, Tim
Betts, Keith A.
Patel, Pankaj
Liu, Jianzhong
Sun, Rochelle
Fleischmann, Roy
author_sort Conaghan, Philip
collection PubMed
description INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease requiring long-term treatment. Upadacitinib (UPA), a Janus kinase (JAK) inhibitor, is a new treatment for RA. The benefit–risk profile of a medication is best understood by evaluating the number needed to treat (NNT) and the number needed to harm (NNH). This analysis evaluated the comparative risk–benefit of UPA versus adalimumab (ADA). METHODS: Post-hoc analyses were performed using data from the SELECT-COMPARE trial of UPA versus placebo (PBO) and UPA versus ADA among patients with active RA who remained on stable methotrexate (MTX) treatment and had an inadequate response; patients who failed to achieve response were rescued by predefined criteria—PBO or ADA switch to UPA, and UPA switch to ADA (all patients on PBO were switched to UPA at week 26). This analysis assessed efficacy and adverse events of special interest (AESIs) at week 26, 48, and 156 (3 years). NNT and NNH (95% confidence intervals) values were calculated between UPA versus ADA for all time points, and between UPA versus PBO for week 26. NNT and NNH values were applied to a hypothetical cohort of 100 patients to estimate the comparative efficacy and safety profiles. RESULTS: UPA consistently showed greater efficacy than ADA, as evidenced by NNT values < 10 for achievement of Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) of < 2.6 and ≤ 3.2, respectively, and functional improvement. Based on indices for disease assessment other than the DAS28-CRP, remission outcomes were higher with UPA versus ADA over 26 weeks (NNTs: 7–12), 48 weeks (NNTs: 9–16), and 156 weeks (NNTs: 9–15). With the exception of herpes zoster, other AESIs demonstrated a similar risk with UPA versus ADA. CONCLUSION: In patients with active RA despite MTX use, UPA demonstrated an incremental achievement of clinical outcomes compared to ADA together with a similar profile of AESIs with ADA (with the exception of herpes zoster). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40744-021-00399-5.
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spelling pubmed-88142622022-02-16 Benefit–Risk Analysis of Upadacitinib Compared with Adalimumab in the Treatment of Patients with Moderate-to-Severe Rheumatoid Arthritis Conaghan, Philip Cohen, Stanley Burmester, Gerd Mysler, Eduardo Nash, Peter Tanaka, Yoshiya Rigby, William Patel, Jayeshkumar Shaw, Tim Betts, Keith A. Patel, Pankaj Liu, Jianzhong Sun, Rochelle Fleischmann, Roy Rheumatol Ther Original Research INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease requiring long-term treatment. Upadacitinib (UPA), a Janus kinase (JAK) inhibitor, is a new treatment for RA. The benefit–risk profile of a medication is best understood by evaluating the number needed to treat (NNT) and the number needed to harm (NNH). This analysis evaluated the comparative risk–benefit of UPA versus adalimumab (ADA). METHODS: Post-hoc analyses were performed using data from the SELECT-COMPARE trial of UPA versus placebo (PBO) and UPA versus ADA among patients with active RA who remained on stable methotrexate (MTX) treatment and had an inadequate response; patients who failed to achieve response were rescued by predefined criteria—PBO or ADA switch to UPA, and UPA switch to ADA (all patients on PBO were switched to UPA at week 26). This analysis assessed efficacy and adverse events of special interest (AESIs) at week 26, 48, and 156 (3 years). NNT and NNH (95% confidence intervals) values were calculated between UPA versus ADA for all time points, and between UPA versus PBO for week 26. NNT and NNH values were applied to a hypothetical cohort of 100 patients to estimate the comparative efficacy and safety profiles. RESULTS: UPA consistently showed greater efficacy than ADA, as evidenced by NNT values < 10 for achievement of Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) of < 2.6 and ≤ 3.2, respectively, and functional improvement. Based on indices for disease assessment other than the DAS28-CRP, remission outcomes were higher with UPA versus ADA over 26 weeks (NNTs: 7–12), 48 weeks (NNTs: 9–16), and 156 weeks (NNTs: 9–15). With the exception of herpes zoster, other AESIs demonstrated a similar risk with UPA versus ADA. CONCLUSION: In patients with active RA despite MTX use, UPA demonstrated an incremental achievement of clinical outcomes compared to ADA together with a similar profile of AESIs with ADA (with the exception of herpes zoster). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40744-021-00399-5. Springer Healthcare 2021-11-23 /pmc/articles/PMC8814262/ /pubmed/34816388 http://dx.doi.org/10.1007/s40744-021-00399-5 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
Conaghan, Philip
Cohen, Stanley
Burmester, Gerd
Mysler, Eduardo
Nash, Peter
Tanaka, Yoshiya
Rigby, William
Patel, Jayeshkumar
Shaw, Tim
Betts, Keith A.
Patel, Pankaj
Liu, Jianzhong
Sun, Rochelle
Fleischmann, Roy
Benefit–Risk Analysis of Upadacitinib Compared with Adalimumab in the Treatment of Patients with Moderate-to-Severe Rheumatoid Arthritis
title Benefit–Risk Analysis of Upadacitinib Compared with Adalimumab in the Treatment of Patients with Moderate-to-Severe Rheumatoid Arthritis
title_full Benefit–Risk Analysis of Upadacitinib Compared with Adalimumab in the Treatment of Patients with Moderate-to-Severe Rheumatoid Arthritis
title_fullStr Benefit–Risk Analysis of Upadacitinib Compared with Adalimumab in the Treatment of Patients with Moderate-to-Severe Rheumatoid Arthritis
title_full_unstemmed Benefit–Risk Analysis of Upadacitinib Compared with Adalimumab in the Treatment of Patients with Moderate-to-Severe Rheumatoid Arthritis
title_short Benefit–Risk Analysis of Upadacitinib Compared with Adalimumab in the Treatment of Patients with Moderate-to-Severe Rheumatoid Arthritis
title_sort benefit–risk analysis of upadacitinib compared with adalimumab in the treatment of patients with moderate-to-severe rheumatoid arthritis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814262/
https://www.ncbi.nlm.nih.gov/pubmed/34816388
http://dx.doi.org/10.1007/s40744-021-00399-5
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