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      Real world long-term impact of intensive treatment on disease activity, disability and health-related quality of life in rheumatoid arthritis

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          Abstract

          Background

          The emphasis on treating rheumatoid arthritis (RA) intensively reduces disease activity but its impact in routine care is uncertain. We evaluated temporal changes in disease activities and outcomes in a 10-year prospective observational cohort study of patients in routine care at one unit.

          Methods

          The Guy’s and St Thomas’ RA cohort was established in 2005. It involved most RA patients managed in this hospital. Clinical diagnoses of RA were made by rheumatologists. Patients were seen regularly in routine care. Each visit included measurement of disease activity scores for 28 joints (DAS28), health assessment questionnaire scores (HAQ) and EuroQol scores. Patients received intensive treatments targeting DAS28 remission.

          Results

          In 1693 RA patients mean DAS28 scores fell from 2005 to 15 by 11% from 4.08 (95% CI: 3.91, 4.25) in 2005 to 3.64 (3.34, 3.78); these falls were highly significant ( p < 0.001). DAS28 components: swollen joint counts fell by 32% and ESR by 24%; in contrast tender joint counts and patient global assessments showed minimal or no reductions. The reduction in DAS28 scores was predominantly between 2005 and 2010, with no falls from 2011 onwards. Associated with falls in mean DAS28s, patients achieving remission increased (18% in 2005; 27% in 2015) and the number with active disease (DAS28 > 5.1) decreased (25% in 2005; 16% in 2015). In 752 patients seen at least annually for 3 years, persisting remission (68 patients) and intermittent remission (376 patients) were associated with less disability and better health related quality of life. Over time biologic use increased, but they were used infrequently in patients in persistent remission.

          Conclusions

          Over 10 years an intensive management strategy in a routine practice setting increased combination DMARD and biologic use: disease activity levels declined; this association is in keeping with a causal relationship. Patients who achieved remission, even transiently, had better functional outcomes than patients never achieving remission.

          Electronic supplementary material

          The online version of this article (10.1186/s41927-019-0054-y) contains supplementary material, which is available to authorized users.

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          Most cited references39

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          Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial

          Lee Smolen, R B Landewé, P J Mease … (2008)
          Background: Certolizumab pegol is a PEGylated tumour necrosis factor inhibitor. Objective: To evaluate the efficacy and safety of certolizumab pegol versus placebo, plus methotrexate (MTX), in patients with active rheumatoid arthritis (RA). Methods: An international, multicentre, phase 3, randomised, double-blind, placebo-controlled study in active adult-onset RA. Patients (n = 619) were randomised 2:2:1 to subcutaneous certolizumab pegol (liquid formulation) 400 mg at weeks 0, 2 and 4 followed by 200 mg or 400 mg plus MTX, or placebo plus MTX, every 2 weeks for 24 weeks. The primary end point was ACR20 response at week 24. Secondary end points included ACR50 and ACR70 responses, change from baseline in modified Total Sharp Score, ACR core set variables and physical function. Results: Significantly more patients in the certolizumab pegol 200 mg and 400 mg groups achieved an ACR20 response versus placebo (p⩽0.001); rates were 57.3%, 57.6% and 8.7%, respectively. Certolizumab pegol 200 and 400 mg also significantly inhibited radiographic progression; mean changes from baseline in mTSS at week 24 were 0.2 and −0.4, respectively, versus 1.2 for placebo (rank analysis p⩽0.01). Certolizumab pegol-treated patients reported rapid and significant improvements in physical function versus placebo; mean changes from baseline in HAQ-DI at week 24 were −0.50 and −0.50, respectively, versus −0.14 for placebo (p⩽0.001). Most adverse events were mild or moderate, with low incidence of withdrawals due to adverse events. Five patients developed tuberculosis. Conclusion: Certolizumab pegol plus MTX was more efficacious than placebo plus MTX, rapidly and significantly improving signs and symptoms of RA and physical function and inhibiting radiographic progression. Trial registration number: NCT00175877
          Article 0 comments Cited 127 times – based on 0 reviews     Review now
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            The relationship between disease activity, joint destruction, and functional capacity over the course of rheumatoid arthritis.

            D Riel, J. M. Dijk, Lambertus Kiemeney … (2001)
            To investigate the relationship between functional capacity, disease activity, and joint destruction over the course of rheumatoid arthritis (RA). The followup data on 378 patients with early RA (duration <1 year), included in an open, prospective study since 1985 at the Department of Rheumatology of the University Medical Center Nijmegen, were used. Functional capacity, disease activity, and joint destruction were assessed using the Health Assessment Questionnaire disability index (HAQ DI), the Disease Activity Score (DAS), and a modification of the sharp radiographic damage score, respectively. Multiple linear regression was used to model the data collected at 0, 3, 6, and 9 years after study start, to investigate which variables influenced functional capacity during the disease course. A general linear mixed model for longitudinal data, which included the variables identified as significant in the multiple linear regression models and several interaction terms between the variables, was run. On average, the functional capacity of the patients, as measured by the HAQ DI, worsened over the course of the disease after an initial improvement. After an initial reduction in the extent of disease activity, the mean DAS remained more or less stable over the course of the disease. The mean modified sharp joint damage score worsened over the course of the disease, with a slower progression rate later in the disease. In the multiple linear regression at 0, 3, and 6 years after study start, disease activity was found to be an important factor influencing functional capacity, and at 6 and 9 years, joint damage had an important effect on functional capacity. Furthermore, at 6 and 9 years, there was an interaction effect of joint destruction with disease activity. In the general linear mixed model, disease activity, joint damage, and an interaction effect of disease activity and joint damage were the main factors explaining functional capacity. The effect of disease activity and joint destruction on functional capacity changes over the course of the disease. In early RA, functional capacity is most associated with disease activity, and in late disease, with joint damage.
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              The Disease Activity Score (DAS) and the Disease Activity Score using 28 joint counts (DAS28) in the management of rheumatoid arthritis.

              Lisanne Renskers, Piet van Riel (2016)
              In rheumatoid arthritis (RA), disease activity cannot be measured in all individual patients according to a single variable. The Disease Activity Score (DAS) and the DAS28 have been developed to measure disease activity in RA both in daily clinical practice as well as in clinical trials on a group as well as individual level. The DAS/DAS28 is a continuous measure of RA disease activity that combines information from swollen joints, tender joints, acute phase response and general health. The DAS-based EULAR response criteria were primarily developed to be used in clinical trials. The EULAR response criteria classify individual patients as non-, moderate, or good responders, dependent on the magnitude of change and level of disease activity reached. In addition, already in the early nineties, cut points were developed to categorise patients in remission. The DAS28 is incorporated in several electronic patient records and web-based systems for monitoring purposes in daily clinical practice. In addition to this, it is being used in combination with patient-reported outcome measures (PROMs) to facilitate self-monitoring.
              Article 0 comments Cited 87 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Nicola J. Gullick: Nicola.Gullick@uhcw.nhs.uk
                Fowzia Ibrahim: fowzia.ibrahim@kcl.ac.uk
                Ian C. Scott: i.scott@keele.ac.uk
                Alexandra Vincent: alexandra.vincent@gstt.nhs.uk
                Andrew P. Cope: andrew.cope@kcl.ac.uk
                Toby Garrood: toby.garrood@gstt.nhs.uk
                Gabriel S. Panayi: gabriel.panayi@kcl.ac.uk
                David L. Scott: dscott1@nhs.net
                Bruce W. Kirkham: bruce.kirkham@gstt.nhs.uk
                Journal
                Journal ID (nlm-ta): BMC Rheumatol
                Journal ID (iso-abbrev): BMC Rheumatol
                Title: BMC rheumatology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 2520-1026
                Publication date (Electronic): 25 February 2019
                Publication date PMC-release: 25 February 2019
                Publication date Collection: 2019
                Volume: 3
                Electronic Location Identifier: 6
                Affiliations
                [1 ]GRID grid.15628.38, Department of Rheumatology, , University Hospitals Coventry and Warwickshire NHS Trust, ; Coventry, UK
                [2 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Department of Rheumatology, , 3rd Floor, Weston Education Centre, King’s College London, ; Cutcombe Road, London, UK
                [3 ]ISNI 0000 0004 0415 6205, GRID grid.9757.c, Research Institute for Primary Care & Health Sciences, Primary Care Sciences, , Keele University, ; Keele, Staffordshire UK
                [4 ]ISNI 0000 0004 0417 8199, GRID grid.413807.9, Department of Rheumatology, , Haywood Hospital, High Lane, ; Burslem, Staffordshire UK
                [5 ]GRID grid.239826.4, Department of Rheumatology, Guy’s and St Thomas’ NHS Trust, , 4th Floor, Tower Wing, Guy’s Hospital, ; Great Maze Pond, London, UK
                [6 ]ISNI 0000 0001 2322 6764, GRID grid.13097.3c, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, , 1st Floor, New Hunt’s House, Guy’s Campus, King’s College London, ; Great Maze Pond, London, UK
                Article
                Publisher ID: 54
                DOI: 10.1186/s41927-019-0054-y
                PMC ID: 6390620
                SO-VID: 4cd009d6-3b25-49be-a185-a7dc1d85bce2
                Copyright © © The Author(s) 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 6 August 2018
                Date accepted : 25 January 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100007602, Programme Grants for Applied Research;
                Award ID: RP-PG-0610-10066
                Categories
                Subject: Research Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                Keywords: temporal ra change,intensive treatment,rheumatoid arthritis
                Data availability:
                Keywords: temporal ra change, intensive treatment, rheumatoid arthritis

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