Analysis of Disease Activity Metrics in a Methotrexate Withdrawal Study among Patients with Rheumatoid Arthritis Treated with Tofacitinib plus Methotrexate
Abstract 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 Clin...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Adis, Springer Healthcare
2022-12-01
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| Series: | Rheumatology and Therapy |
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| Online Access: | https://doi.org/10.1007/s40744-022-00511-3 |
| _version_ | 1797863605995044864 |
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| author | Roy Fleischmann Boulos Haraoui Maya H. Buch David Gold Gosford Sawyerr Harry Shi Annette Diehl Kristen Lee |
| author_facet | Roy Fleischmann Boulos Haraoui Maya H. Buch David Gold Gosford Sawyerr Harry Shi Annette Diehl Kristen Lee |
| author_sort | Roy Fleischmann |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-09T22:38:08Z |
| format | Article |
| id | doaj.art-5b697dcdf880453bb81e36e0676fe470 |
| institution | Directory Open Access Journal |
| issn | 2198-6576 2198-6584 |
| language | English |
| last_indexed | 2024-04-09T22:38:08Z |
| publishDate | 2022-12-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Rheumatology and Therapy |
| spelling | doaj.art-5b697dcdf880453bb81e36e0676fe4702023-03-22T12:20:56ZengAdis, Springer HealthcareRheumatology and Therapy2198-65762198-65842022-12-0110237538610.1007/s40744-022-00511-3Analysis of Disease Activity Metrics in a Methotrexate Withdrawal Study among Patients with Rheumatoid Arthritis Treated with Tofacitinib plus MethotrexateRoy Fleischmann0Boulos Haraoui1Maya H. Buch2David Gold3Gosford Sawyerr4Harry Shi5Annette Diehl6Kristen Lee7Metroplex Clinical Research Center and University of Texas Southwestern Medical CenterInstitut de Rhumatologie de MontréalCentre for Musculoskeletal Research, University of Manchester, and NIHR Manchester Biomedical Research CentrePfizer Canada ULCPfizer IncPfizer IncPfizer IncPfizer IncAbstract 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.https://doi.org/10.1007/s40744-022-00511-3Rheumatoid arthritisInflammationMethotrexateTherapeutics |
| spellingShingle | Roy Fleischmann Boulos Haraoui Maya H. Buch David Gold Gosford Sawyerr Harry Shi Annette Diehl Kristen Lee Analysis of Disease Activity Metrics in a Methotrexate Withdrawal Study among Patients with Rheumatoid Arthritis Treated with Tofacitinib plus Methotrexate Rheumatology and Therapy Rheumatoid arthritis Inflammation Methotrexate Therapeutics |
| 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 | Rheumatoid arthritis Inflammation Methotrexate Therapeutics |
| url | https://doi.org/10.1007/s40744-022-00511-3 |
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