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Analysis of Disease Activity Metrics in a Methotrexate Withdrawal Study among Patients with Rheumatoid Arthritis Treated with Tofacitinib plus Methotrexate
INTRODUCTION: The objective of this analysis was to assess disease activity metrics using a variety of disease outcome measures following methotrexate (MTX) withdrawal in ORAL Shift, a phase 3b/4 study of tofacitinib with/without MTX, in patients with rheumatoid arthritis (RA) achieving Clinical Dis...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Healthcare
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10011257/ https://www.ncbi.nlm.nih.gov/pubmed/36534208 http://dx.doi.org/10.1007/s40744-022-00511-3 |
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author | Fleischmann, Roy Haraoui, Boulos Buch, Maya H. Gold, David Sawyerr, Gosford Shi, Harry Diehl, Annette Lee, Kristen |
author_facet | Fleischmann, Roy Haraoui, Boulos Buch, Maya H. Gold, David Sawyerr, Gosford Shi, Harry Diehl, Annette Lee, Kristen |
author_sort | Fleischmann, Roy |
collection | PubMed |
description | INTRODUCTION: The objective of this analysis was to assess disease activity metrics using a variety of disease outcome measures following methotrexate (MTX) withdrawal in ORAL Shift, a phase 3b/4 study of tofacitinib with/without MTX, in patients with rheumatoid arthritis (RA) achieving Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA). METHODS: Patients aged ≥ 18 years with active RA and an inadequate response to MTX received open-label tofacitinib modified-release 11 mg once daily plus MTX for 24 weeks. In the double-blind MTX withdrawal phase, those who had achieved CDAI LDA (≤ 10) at week 24 were randomised 1:1 to receive tofacitinib monotherapy or continued tofacitinib plus MTX. Efficacy analyses were performed in subgroups defined by whether remission and/or LDA had been achieved at week 24 with: Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)], Routine Assessment of Patient Index Data 3 (RAPID3), CDAI and Simplified Disease Activity Index (SDAI); or DAS28-4[C-reactive protein(CRP)] < 2.4/ < 2.6/ < 2.9/ ≤ 3.2. RESULTS: Five hundred and thirty patients received treatment in the double-blind MTX withdrawal phase. Proportions of patients achieving each disease activity criterion at week 24 varied by metric. Across disease activity metrics [excluding DAS28-4(ESR) remission], 58–89% of patients per group, and numerically more patients receiving tofacitinib plus MTX, achieved the same criterion at week 48 as at week 24. Differences between groups in least squares mean change from baseline (Δ) DAS28-4(ESR) from week 24–48 favoured tofacitinib plus MTX (nominal p values < 0.05). RAPID3 and DAS28-4(CRP) estimated a higher proportion of patients with acceptable disease state versus DAS28-4(ESR), CDAI remission and SDAI remission. CONCLUSION: Response rates at the beginning of the double-blind phase varied across metrics. A consistent trend towards higher response rates with tofacitinib plus MTX was observed across metrics after randomisation, with nominal differences in DAS28-4(ESR) responses. Compared with continued combination therapy, MTX withdrawal did not lead to a clinically meaningful reduction in the response to tofacitinib. DAS28-4(CRP) and RAPID3 were the least stringent metrics. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02831855. |
format | Online Article Text |
id | pubmed-10011257 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Healthcare |
record_format | MEDLINE/PubMed |
spelling | pubmed-100112572023-03-15 Analysis of Disease Activity Metrics in a Methotrexate Withdrawal Study among Patients with Rheumatoid Arthritis Treated with Tofacitinib plus Methotrexate Fleischmann, Roy Haraoui, Boulos Buch, Maya H. Gold, David Sawyerr, Gosford Shi, Harry Diehl, Annette Lee, Kristen Rheumatol Ther Original Research INTRODUCTION: The objective of this analysis was to assess disease activity metrics using a variety of disease outcome measures following methotrexate (MTX) withdrawal in ORAL Shift, a phase 3b/4 study of tofacitinib with/without MTX, in patients with rheumatoid arthritis (RA) achieving Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA). METHODS: Patients aged ≥ 18 years with active RA and an inadequate response to MTX received open-label tofacitinib modified-release 11 mg once daily plus MTX for 24 weeks. In the double-blind MTX withdrawal phase, those who had achieved CDAI LDA (≤ 10) at week 24 were randomised 1:1 to receive tofacitinib monotherapy or continued tofacitinib plus MTX. Efficacy analyses were performed in subgroups defined by whether remission and/or LDA had been achieved at week 24 with: Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)], Routine Assessment of Patient Index Data 3 (RAPID3), CDAI and Simplified Disease Activity Index (SDAI); or DAS28-4[C-reactive protein(CRP)] < 2.4/ < 2.6/ < 2.9/ ≤ 3.2. RESULTS: Five hundred and thirty patients received treatment in the double-blind MTX withdrawal phase. Proportions of patients achieving each disease activity criterion at week 24 varied by metric. Across disease activity metrics [excluding DAS28-4(ESR) remission], 58–89% of patients per group, and numerically more patients receiving tofacitinib plus MTX, achieved the same criterion at week 48 as at week 24. Differences between groups in least squares mean change from baseline (Δ) DAS28-4(ESR) from week 24–48 favoured tofacitinib plus MTX (nominal p values < 0.05). RAPID3 and DAS28-4(CRP) estimated a higher proportion of patients with acceptable disease state versus DAS28-4(ESR), CDAI remission and SDAI remission. CONCLUSION: Response rates at the beginning of the double-blind phase varied across metrics. A consistent trend towards higher response rates with tofacitinib plus MTX was observed across metrics after randomisation, with nominal differences in DAS28-4(ESR) responses. Compared with continued combination therapy, MTX withdrawal did not lead to a clinically meaningful reduction in the response to tofacitinib. DAS28-4(CRP) and RAPID3 were the least stringent metrics. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02831855. Springer Healthcare 2022-12-19 /pmc/articles/PMC10011257/ /pubmed/36534208 http://dx.doi.org/10.1007/s40744-022-00511-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis 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 Fleischmann, Roy Haraoui, Boulos Buch, Maya H. Gold, David Sawyerr, Gosford Shi, Harry Diehl, Annette Lee, Kristen Analysis of Disease Activity Metrics in a Methotrexate Withdrawal Study among Patients with Rheumatoid Arthritis Treated with Tofacitinib plus Methotrexate |
title | Analysis of Disease Activity Metrics in a Methotrexate Withdrawal Study among Patients with Rheumatoid Arthritis Treated with Tofacitinib plus Methotrexate |
title_full | Analysis of Disease Activity Metrics in a Methotrexate Withdrawal Study among Patients with Rheumatoid Arthritis Treated with Tofacitinib plus Methotrexate |
title_fullStr | Analysis of Disease Activity Metrics in a Methotrexate Withdrawal Study among Patients with Rheumatoid Arthritis Treated with Tofacitinib plus Methotrexate |
title_full_unstemmed | Analysis of Disease Activity Metrics in a Methotrexate Withdrawal Study among Patients with Rheumatoid Arthritis Treated with Tofacitinib plus Methotrexate |
title_short | Analysis of Disease Activity Metrics in a Methotrexate Withdrawal Study among Patients with Rheumatoid Arthritis Treated with Tofacitinib plus Methotrexate |
title_sort | analysis of disease activity metrics in a methotrexate withdrawal study among patients with rheumatoid arthritis treated with tofacitinib plus methotrexate |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10011257/ https://www.ncbi.nlm.nih.gov/pubmed/36534208 http://dx.doi.org/10.1007/s40744-022-00511-3 |
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