Patterns of comorbidities differentially affect long-term functional evolution and disease activity in patients with ‘difficult to treat’ rheumatoid arthritis

Background Characterisation of the long-term outcome of patients with ‘difficult to treat’ (D2T) rheumatoid arthritis and factors contributing to its evolution are unknown. Herein, we explored the heterogeneity and contributing factors of D2T long-term outcome.Methods Patients included from a prospe...

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Main Authors: Prodromos Sidiropoulos, George Bertsias, Argyro Repa, Eleni Kalogiannaki, Antonios Bertsias, Nestor Avgoustidis, Sofia Pitsigavdaki, Irini D Flouri
Format: Article
Language:English
Published: BMJ Publishing Group 2024-02-01
Series:RMD Open
Online Access:https://rmdopen.bmj.com/content/10/1/e003808.full
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author Prodromos Sidiropoulos
George Bertsias
Argyro Repa
Eleni Kalogiannaki
Antonios Bertsias
Nestor Avgoustidis
Sofia Pitsigavdaki
Irini D Flouri
author_facet Prodromos Sidiropoulos
George Bertsias
Argyro Repa
Eleni Kalogiannaki
Antonios Bertsias
Nestor Avgoustidis
Sofia Pitsigavdaki
Irini D Flouri
author_sort Prodromos Sidiropoulos
collection DOAJ
description Background Characterisation of the long-term outcome of patients with ‘difficult to treat’ (D2T) rheumatoid arthritis and factors contributing to its evolution are unknown. Herein, we explored the heterogeneity and contributing factors of D2T long-term outcome.Methods Patients included from a prospective single centre cohort study. The EULAR definition of D2T was applied. Longitudinal clustering of functional status (modified Health Assessment Questionnaire (mHAQ)) and disease activity (Disease Activity Score-28 (DAS28)) were assessed using latent-class trajectory analysis. Multiple linear mixed models were used to examine the impact of comorbidities and their clusters on the long-term outcome.Results 251 out of 1264 patients (19.9%) were identified as D2T. Younger age, fibromyalgia, osteoarthritis, DAS28-erythrocyte sedimentation rate (ESR) at first biological or targeted synthetic disease-modifying antirheumatic drug (b/ts-DMARD) initiation and failure to reduce DAS28-ESR scores within the first 6 months of b/ts-DMARD therapy were significant predictors of patients becoming D2T. Long-term follow-up (total of 5872 person-years) revealed four groups of functional status evolution: 18.2% had stable, mildly compromised mHAQ (mean 0.41), 39.9% had gradual improvement (1.21–0.87) and two groups had either slow deterioration or stable significant functional impairment (HAQ>1). Similarly, four distinct groups of disease activity evolution were identified. Among the different clusters of comorbidities assessed, presence of ‘mental-health and pain-related illnesses’ or ‘metabolic diseases’ had significant contribution to mHAQ worsening (p<0.0001 for both) and DAS28 evolution (p<0.0001 and p=0.018, respectively).Conclusion D2T patients represent a heterogeneous group in terms of long-term disease course. Mental-health/pain-related illnesses as well as metabolic diseases contribute to long-term adverse outcomes and should be targeted in order to optimise the prognosis of this subset of rheumatoid arthritis.
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spelling doaj-art-0f0a233a74b046ee84838cb7722bcc8b2025-08-20T01:47:26ZengBMJ Publishing GroupRMD Open2056-59332024-02-0110110.1136/rmdopen-2023-003808Patterns of comorbidities differentially affect long-term functional evolution and disease activity in patients with ‘difficult to treat’ rheumatoid arthritisProdromos Sidiropoulos0George Bertsias1Argyro Repa2Eleni Kalogiannaki3Antonios Bertsias4Nestor Avgoustidis5Sofia Pitsigavdaki6Irini D Flouri7Division of Immunity, Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology Hellas, Heraklion, GreeceLaboratory of Autoimmunity-Inflammation, Institute of Molecular Biology and Biotechnology, Heraklion, Crete, GreeceRheumatology and Clinical Immunology, University of Crete School of Medicine, Heraklion, GreeceRheumatology, Clinical Immunology and Allergy Department, School of Medicine, University of Crete, Heraklion, Crete, GreeceRheumatology, Clinical Immunology and Allergy Department, School of Medicine, University of Crete, Heraklion, Crete, GreeceRheumatology and Clinical Immunology, University of Crete School of Medicine, Heraklion, GreeceRheumatology and Clinical Immunology, University of Crete School of Medicine, Heraklion, GreeceRheumatology, Clinical Immunology and Allergy Department, School of Medicine, University of Crete, Heraklion, Crete, GreeceBackground Characterisation of the long-term outcome of patients with ‘difficult to treat’ (D2T) rheumatoid arthritis and factors contributing to its evolution are unknown. Herein, we explored the heterogeneity and contributing factors of D2T long-term outcome.Methods Patients included from a prospective single centre cohort study. The EULAR definition of D2T was applied. Longitudinal clustering of functional status (modified Health Assessment Questionnaire (mHAQ)) and disease activity (Disease Activity Score-28 (DAS28)) were assessed using latent-class trajectory analysis. Multiple linear mixed models were used to examine the impact of comorbidities and their clusters on the long-term outcome.Results 251 out of 1264 patients (19.9%) were identified as D2T. Younger age, fibromyalgia, osteoarthritis, DAS28-erythrocyte sedimentation rate (ESR) at first biological or targeted synthetic disease-modifying antirheumatic drug (b/ts-DMARD) initiation and failure to reduce DAS28-ESR scores within the first 6 months of b/ts-DMARD therapy were significant predictors of patients becoming D2T. Long-term follow-up (total of 5872 person-years) revealed four groups of functional status evolution: 18.2% had stable, mildly compromised mHAQ (mean 0.41), 39.9% had gradual improvement (1.21–0.87) and two groups had either slow deterioration or stable significant functional impairment (HAQ>1). Similarly, four distinct groups of disease activity evolution were identified. Among the different clusters of comorbidities assessed, presence of ‘mental-health and pain-related illnesses’ or ‘metabolic diseases’ had significant contribution to mHAQ worsening (p<0.0001 for both) and DAS28 evolution (p<0.0001 and p=0.018, respectively).Conclusion D2T patients represent a heterogeneous group in terms of long-term disease course. Mental-health/pain-related illnesses as well as metabolic diseases contribute to long-term adverse outcomes and should be targeted in order to optimise the prognosis of this subset of rheumatoid arthritis.https://rmdopen.bmj.com/content/10/1/e003808.full
spellingShingle Prodromos Sidiropoulos
George Bertsias
Argyro Repa
Eleni Kalogiannaki
Antonios Bertsias
Nestor Avgoustidis
Sofia Pitsigavdaki
Irini D Flouri
Patterns of comorbidities differentially affect long-term functional evolution and disease activity in patients with ‘difficult to treat’ rheumatoid arthritis
RMD Open
title Patterns of comorbidities differentially affect long-term functional evolution and disease activity in patients with ‘difficult to treat’ rheumatoid arthritis
title_full Patterns of comorbidities differentially affect long-term functional evolution and disease activity in patients with ‘difficult to treat’ rheumatoid arthritis
title_fullStr Patterns of comorbidities differentially affect long-term functional evolution and disease activity in patients with ‘difficult to treat’ rheumatoid arthritis
title_full_unstemmed Patterns of comorbidities differentially affect long-term functional evolution and disease activity in patients with ‘difficult to treat’ rheumatoid arthritis
title_short Patterns of comorbidities differentially affect long-term functional evolution and disease activity in patients with ‘difficult to treat’ rheumatoid arthritis
title_sort patterns of comorbidities differentially affect long term functional evolution and disease activity in patients with difficult to treat rheumatoid arthritis
url https://rmdopen.bmj.com/content/10/1/e003808.full
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