Impact of Dose Tapering of Tumor Necrosis Factor Inhibitor on Radiographic Progression in Ankylosing Spondylitis

To investigate the impact of dose reduction of tumor necrosis factor inhibitor (TNFi) on radiographic progression in ankylosing spondylitis (AS). One hundred and sixty-five patients treated with etanercept or adalimumab were selected from a consecutive single-center observational cohort based on the...

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Veröffentlicht in:PloS one 2016-12, Vol.11 (12), p.e0168958-e0168958
Hauptverfasser: Park, Jun Won, Kwon, Hyun Mi, Park, Jin Kyun, Choi, Ja-Young, Lee, Eun Bong, Song, Yeong Wook, Lee, Eun Young
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creator Park, Jun Won
Kwon, Hyun Mi
Park, Jin Kyun
Choi, Ja-Young
Lee, Eun Bong
Song, Yeong Wook
Lee, Eun Young
description To investigate the impact of dose reduction of tumor necrosis factor inhibitor (TNFi) on radiographic progression in ankylosing spondylitis (AS). One hundred and sixty-five patients treated with etanercept or adalimumab were selected from a consecutive single-center observational cohort based on the availability of radiographs at baseline and after two- and/or four-years of follow up. Radiographs were assessed by two blinded readers using the modified Stokes AS Spinal Score (mSASSS). Radiographic progression in patients treated with standard-dose TNFi (standard-dose group, n = 49) was compared with patients whose dosage was tapered during the treatment (tapering group, n = 116) using linear mixed models. Baseline characteristics between two groups were comparable except for higher BASDAI (7.1 vs. 6.3, p = 0.003) in the standard-dose group. At two years after the treatment, mean dose quotient (S.D.) of the tapering group was 0.59 (0.17). During follow up, rate of radiographic progression in overall patients was 0.90 mSASSS units/year. Radiographic progression over time between the two groups was similar at the entire group level. However, in the subgroup of patients with baseline syndesmophytes, progression occurred significantly faster in the tapering group after the adjustment for baseline status (1.23 vs. 1.72 mSASSS units/year, p = 0.023). Results were consistent when radiographic progression was assessed by the number of newly developed syndesmophytes (0.52 vs. 0.73/year, p = 0.047). Sensitivity analysis after multiple imputation of missing radiographs also showed similar results. A dose tapering strategy of TNFi is associated with more rapid radiographic progression in AS patients who have syndesmophytes at baseline.
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One hundred and sixty-five patients treated with etanercept or adalimumab were selected from a consecutive single-center observational cohort based on the availability of radiographs at baseline and after two- and/or four-years of follow up. Radiographs were assessed by two blinded readers using the modified Stokes AS Spinal Score (mSASSS). Radiographic progression in patients treated with standard-dose TNFi (standard-dose group, n = 49) was compared with patients whose dosage was tapered during the treatment (tapering group, n = 116) using linear mixed models. Baseline characteristics between two groups were comparable except for higher BASDAI (7.1 vs. 6.3, p = 0.003) in the standard-dose group. At two years after the treatment, mean dose quotient (S.D.) of the tapering group was 0.59 (0.17). During follow up, rate of radiographic progression in overall patients was 0.90 mSASSS units/year. Radiographic progression over time between the two groups was similar at the entire group level. However, in the subgroup of patients with baseline syndesmophytes, progression occurred significantly faster in the tapering group after the adjustment for baseline status (1.23 vs. 1.72 mSASSS units/year, p = 0.023). Results were consistent when radiographic progression was assessed by the number of newly developed syndesmophytes (0.52 vs. 0.73/year, p = 0.047). Sensitivity analysis after multiple imputation of missing radiographs also showed similar results. A dose tapering strategy of TNFi is associated with more rapid radiographic progression in AS patients who have syndesmophytes at baseline.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0168958</identifier><identifier>PMID: 28033420</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adalimumab - pharmacology ; Adalimumab - therapeutic use ; Adult ; Analysis ; Ankylosing spondylitis ; Arthritis ; Biology and Life Sciences ; Care and treatment ; Cohort Studies ; Development and progression ; Disease Progression ; Dose-Response Relationship, Drug ; Drug dosages ; Etanercept ; Etanercept - pharmacology ; Etanercept - therapeutic use ; Female ; Follow-Up Studies ; Genetic aspects ; Humans ; Inflammation ; Inhibitors ; Internal medicine ; Male ; Medicine ; Medicine and health sciences ; Monoclonal antibodies ; Necrosis ; NMR ; Nuclear magnetic resonance ; Patients ; Physiological aspects ; Radiographs ; Radiography ; Research and Analysis Methods ; Review boards ; Rheumatic diseases ; Rheumatism ; Rheumatology ; Sensitivity analysis ; Spondylitis ; Spondylitis, Ankylosing - diagnostic imaging ; Spondylitis, Ankylosing - drug therapy ; Studies ; Tapering ; Time Factors ; TNF inhibitors ; Tumor necrosis factor ; Tumor Necrosis Factor-alpha - antagonists &amp; inhibitors ; Tumor necrosis factor-TNF</subject><ispartof>PloS one, 2016-12, Vol.11 (12), p.e0168958-e0168958</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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One hundred and sixty-five patients treated with etanercept or adalimumab were selected from a consecutive single-center observational cohort based on the availability of radiographs at baseline and after two- and/or four-years of follow up. Radiographs were assessed by two blinded readers using the modified Stokes AS Spinal Score (mSASSS). Radiographic progression in patients treated with standard-dose TNFi (standard-dose group, n = 49) was compared with patients whose dosage was tapered during the treatment (tapering group, n = 116) using linear mixed models. Baseline characteristics between two groups were comparable except for higher BASDAI (7.1 vs. 6.3, p = 0.003) in the standard-dose group. At two years after the treatment, mean dose quotient (S.D.) of the tapering group was 0.59 (0.17). During follow up, rate of radiographic progression in overall patients was 0.90 mSASSS units/year. Radiographic progression over time between the two groups was similar at the entire group level. However, in the subgroup of patients with baseline syndesmophytes, progression occurred significantly faster in the tapering group after the adjustment for baseline status (1.23 vs. 1.72 mSASSS units/year, p = 0.023). Results were consistent when radiographic progression was assessed by the number of newly developed syndesmophytes (0.52 vs. 0.73/year, p = 0.047). Sensitivity analysis after multiple imputation of missing radiographs also showed similar results. A dose tapering strategy of TNFi is associated with more rapid radiographic progression in AS patients who have syndesmophytes at baseline.</description><subject>Adalimumab - pharmacology</subject><subject>Adalimumab - therapeutic use</subject><subject>Adult</subject><subject>Analysis</subject><subject>Ankylosing spondylitis</subject><subject>Arthritis</subject><subject>Biology and Life Sciences</subject><subject>Care and treatment</subject><subject>Cohort Studies</subject><subject>Development and progression</subject><subject>Disease Progression</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug dosages</subject><subject>Etanercept</subject><subject>Etanercept - pharmacology</subject><subject>Etanercept - therapeutic use</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Genetic aspects</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inhibitors</subject><subject>Internal medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine and health sciences</subject><subject>Monoclonal antibodies</subject><subject>Necrosis</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Patients</subject><subject>Physiological aspects</subject><subject>Radiographs</subject><subject>Radiography</subject><subject>Research and Analysis Methods</subject><subject>Review boards</subject><subject>Rheumatic diseases</subject><subject>Rheumatism</subject><subject>Rheumatology</subject><subject>Sensitivity analysis</subject><subject>Spondylitis</subject><subject>Spondylitis, Ankylosing - diagnostic imaging</subject><subject>Spondylitis, Ankylosing - drug therapy</subject><subject>Studies</subject><subject>Tapering</subject><subject>Time Factors</subject><subject>TNF inhibitors</subject><subject>Tumor necrosis factor</subject><subject>Tumor Necrosis Factor-alpha - antagonists &amp; 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One hundred and sixty-five patients treated with etanercept or adalimumab were selected from a consecutive single-center observational cohort based on the availability of radiographs at baseline and after two- and/or four-years of follow up. Radiographs were assessed by two blinded readers using the modified Stokes AS Spinal Score (mSASSS). Radiographic progression in patients treated with standard-dose TNFi (standard-dose group, n = 49) was compared with patients whose dosage was tapered during the treatment (tapering group, n = 116) using linear mixed models. Baseline characteristics between two groups were comparable except for higher BASDAI (7.1 vs. 6.3, p = 0.003) in the standard-dose group. At two years after the treatment, mean dose quotient (S.D.) of the tapering group was 0.59 (0.17). During follow up, rate of radiographic progression in overall patients was 0.90 mSASSS units/year. Radiographic progression over time between the two groups was similar at the entire group level. However, in the subgroup of patients with baseline syndesmophytes, progression occurred significantly faster in the tapering group after the adjustment for baseline status (1.23 vs. 1.72 mSASSS units/year, p = 0.023). Results were consistent when radiographic progression was assessed by the number of newly developed syndesmophytes (0.52 vs. 0.73/year, p = 0.047). Sensitivity analysis after multiple imputation of missing radiographs also showed similar results. A dose tapering strategy of TNFi is associated with more rapid radiographic progression in AS patients who have syndesmophytes at baseline.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28033420</pmid><doi>10.1371/journal.pone.0168958</doi><tpages>e0168958</tpages><orcidid>https://orcid.org/0000-0001-6975-8627</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adalimumab - pharmacology
Adalimumab - therapeutic use
Adult
Analysis
Ankylosing spondylitis
Arthritis
Biology and Life Sciences
Care and treatment
Cohort Studies
Development and progression
Disease Progression
Dose-Response Relationship, Drug
Drug dosages
Etanercept
Etanercept - pharmacology
Etanercept - therapeutic use
Female
Follow-Up Studies
Genetic aspects
Humans
Inflammation
Inhibitors
Internal medicine
Male
Medicine
Medicine and health sciences
Monoclonal antibodies
Necrosis
NMR
Nuclear magnetic resonance
Patients
Physiological aspects
Radiographs
Radiography
Research and Analysis Methods
Review boards
Rheumatic diseases
Rheumatism
Rheumatology
Sensitivity analysis
Spondylitis
Spondylitis, Ankylosing - diagnostic imaging
Spondylitis, Ankylosing - drug therapy
Studies
Tapering
Time Factors
TNF inhibitors
Tumor necrosis factor
Tumor Necrosis Factor-alpha - antagonists & inhibitors
Tumor necrosis factor-TNF
title Impact of Dose Tapering of Tumor Necrosis Factor Inhibitor on Radiographic Progression in Ankylosing Spondylitis
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