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Published in: Arthritis Research & Therapy 1/2017

Open Access 01-12-2017 | Research article

Changes in clinical disease activity are weakly linked to changes in MRI inflammation on treat-to-target escalation of therapy in rheumatoid arthritis

Authors: Fiona M. McQueen, Peter Chapman, Terina Pollock, Dena D’Souza, Arier C. Lee, Nicola Dalbeth, Lisa Stamp, Karen Lindsay, Anthony Doyle

Published in: Arthritis Research & Therapy | Issue 1/2017

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Abstract

Background

Rheumatoid arthritis (RA) treat-to-target (T2T) regimens often use the disease activity score (28 joints) incorporating C-reactive protein (DAS28CRP) as an outcome measure. We compared changes in the DAS28CRP with changes in magnetic resonance imaging (MRI) inflammation on treatment escalation.

Methods

Eighty seropositive RA patients with active disease were enrolled. Group A (N = 57) escalated to another conventional disease-modifying therapy (cDMARD) combination, and Group B (N = 23) to anti-TNF therapy/cDMARDs. Contrast-enhanced 3T-MRI wrist scans were obtained before and 4 months after regimen change. Scan pairs were scored for inflammation (MRI(i)) and damage. Disease activity was assessed using the DAS28CRP.

Results

Eighty patients were enrolled and 66 MRI scan pairs were available for analysis. Intra-reader reliability was high: intraclass correlation coefficient (average) 0.89 (0.56–0.97). ΔDAS28CRP did not differ between groups: Group A, −0.94 (−3.30, 1.61); Group B, −1.53 (−3.59, 0.56) (p = 0.45). ΔMRI(i) also did not differ: Group A, 0 (−25, 10); Group B, −1 (−15, 28) (p = 0.12). Combining groups, ΔMRI(i) correlated weakly with ΔDAS28CRP (Spearman’s 0.36, p = 0.003). Using multiple linear regression analysis adjusting for confounders, ΔDAS28CRP was associated with ΔMRI(i) (p = 0.056). Of the individual MRI measures, only Δtenosynovitis correlated with ΔDAS28CRP (Spearman’s 0.33, p = 0.007). ΔMRI(i) was negatively associated with the MRI erosion score at entry (p = 0.0052).

Conclusions

We report the first study investigating the link between changes in clinical and imaging inflammation in a real-world RA cohort escalating to conventional and biologic DMARDs. The association was significant but relatively weak, suggesting that MRI targets cannot yet be advocated as outcomes for T2T escalation.

Trial registration

ANZCTR 12614000895684. Registered 22 August 2014.
Literature
1.
go back to reference Grigor C, Capell H, Stirling A, McMahon AD, Lock P, Vallance R, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet. 2004;364(9430):263–9.CrossRefPubMed Grigor C, Capell H, Stirling A, McMahon AD, Lock P, Vallance R, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet. 2004;364(9430):263–9.CrossRefPubMed
2.
go back to reference Smolen JS, Landewe R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Annals of the Rheumatic Diseases. 2017;76(6):960–77.CrossRefPubMed Smolen JS, Landewe R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Annals of the Rheumatic Diseases. 2017;76(6):960–77.CrossRefPubMed
4.
go back to reference van Riel PLCM, Fransen J. DAS28: a useful instrument to monitor infliximab treatment in patients with rheumatoid arthritis. Arthritis Research and Therapy. 2005;7(5):189–90.CrossRefPubMedPubMedCentral van Riel PLCM, Fransen J. DAS28: a useful instrument to monitor infliximab treatment in patients with rheumatoid arthritis. Arthritis Research and Therapy. 2005;7(5):189–90.CrossRefPubMedPubMedCentral
5.
go back to reference Prevoo ML, Van ’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis.[see comment]. Arthritis & Rheumatism. 1995;38(1):44–8.CrossRef Prevoo ML, Van ’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis.[see comment]. Arthritis & Rheumatism. 1995;38(1):44–8.CrossRef
6.
go back to reference McQueen FM, Ostergaard M. Established rheumatoid arthritis - new imaging modalities. Baillieres Best Pract Res Clin Rheumatol. 2007;21(5):841–56.CrossRef McQueen FM, Ostergaard M. Established rheumatoid arthritis - new imaging modalities. Baillieres Best Pract Res Clin Rheumatol. 2007;21(5):841–56.CrossRef
7.
go back to reference McQueen FM, McHaffie A, Clarke A, Lee AC, Reeves Q, Curteis B, et al. MRI osteitis predicts cartilage damage at the wrist in RA: a three-year prospective 3T MRI study examining cartilage damage. Arthritis Research and Therapy. 2014;16:R33.CrossRefPubMedPubMedCentral McQueen FM, McHaffie A, Clarke A, Lee AC, Reeves Q, Curteis B, et al. MRI osteitis predicts cartilage damage at the wrist in RA: a three-year prospective 3T MRI study examining cartilage damage. Arthritis Research and Therapy. 2014;16:R33.CrossRefPubMedPubMedCentral
8.
go back to reference Ostergaard M, Peterfy C, Conaghan P, McQueen F, Bird P, Ejbjerg B, et al. OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Core set of MRI acquisitions, joint pathology definitions, and the OMERACT RA-MRI scoring system. J Rheumatol. 2003;30(6):1385–6.PubMed Ostergaard M, Peterfy C, Conaghan P, McQueen F, Bird P, Ejbjerg B, et al. OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Core set of MRI acquisitions, joint pathology definitions, and the OMERACT RA-MRI scoring system. J Rheumatol. 2003;30(6):1385–6.PubMed
9.
go back to reference Haavardsholm EA, Ostergaard M, Ejbjerg BJ, Kvan NP, Kvien TK. Introduction of a novel magnetic resonance imaging tenosynovitis score for rheumatoid arthritis: reliability in a multireader longitudinal study. Annals of the Rheumatic Diseases. 2007;66(9):1216–20.CrossRefPubMedPubMedCentral Haavardsholm EA, Ostergaard M, Ejbjerg BJ, Kvan NP, Kvien TK. Introduction of a novel magnetic resonance imaging tenosynovitis score for rheumatoid arthritis: reliability in a multireader longitudinal study. Annals of the Rheumatic Diseases. 2007;66(9):1216–20.CrossRefPubMedPubMedCentral
10.
go back to reference Brown AK, Quinn MA, Karim Z, Conaghan PG, Peterfy CG, Hensor E, et al. Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying antirheumatic drug-induced clinical remission: evidence from an imaging study may explain structural progression. Arthritis. Rheumatism. 2006;54(12):3761–73.CrossRef Brown AK, Quinn MA, Karim Z, Conaghan PG, Peterfy CG, Hensor E, et al. Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying antirheumatic drug-induced clinical remission: evidence from an imaging study may explain structural progression. Arthritis. Rheumatism. 2006;54(12):3761–73.CrossRef
11.
go back to reference Krabben A, Stomp W, Huizinga TW, van der Heijde D, Bloem JL, Reijnierse M, et al. Concordance between inflammation at physical examination and on MRI in patients with early arthritis. Annals of the Rheumatic Diseases. 2015;74(3):506–12.CrossRefPubMed Krabben A, Stomp W, Huizinga TW, van der Heijde D, Bloem JL, Reijnierse M, et al. Concordance between inflammation at physical examination and on MRI in patients with early arthritis. Annals of the Rheumatic Diseases. 2015;74(3):506–12.CrossRefPubMed
12.
go back to reference McQueen F, Benton N, Perry D, Crabbe J, Robinson E. Bone Edema Scored on Magnetic Resonance Imaging Scans of the Dominant Carpus at Presentation Predicts Radiographic Joint Damage of the Hands and Feet Six Years Later in Patients with Rheumatoid Arthritis. Arthritis Rheum. 2003;48(7):1814–27.CrossRefPubMed McQueen F, Benton N, Perry D, Crabbe J, Robinson E. Bone Edema Scored on Magnetic Resonance Imaging Scans of the Dominant Carpus at Presentation Predicts Radiographic Joint Damage of the Hands and Feet Six Years Later in Patients with Rheumatoid Arthritis. Arthritis Rheum. 2003;48(7):1814–27.CrossRefPubMed
13.
go back to reference Hetland ML, Ejbjerg B, Horslev-Petersen K, Jacobsen S, Vestergaard A, Jurik AG, et al. MRI bone oedema is the strongest predictor of subsequent radiographic progression in early rheumatoid arthritis. Results from a 2-year randomised controlled trial (CIMESTRA). Annals of the Rheumatic Diseases. 2009;68(3):384–90.CrossRefPubMed Hetland ML, Ejbjerg B, Horslev-Petersen K, Jacobsen S, Vestergaard A, Jurik AG, et al. MRI bone oedema is the strongest predictor of subsequent radiographic progression in early rheumatoid arthritis. Results from a 2-year randomised controlled trial (CIMESTRA). Annals of the Rheumatic Diseases. 2009;68(3):384–90.CrossRefPubMed
14.
go back to reference Ostergaard M, Emery P, Conaghan PG, Fleischmann R, Hsia EC, Xu W, et al. Significant improvement in synovitis, osteitis, and bone erosion following golimumab and methotrexate combination therapy as compared with methotrexate alone: a magnetic resonance imaging study of 318 methotrexate-naive rheumatoid arthritis patients. Arthritis. Rheumatism. 2011;63(12):3712–22.CrossRef Ostergaard M, Emery P, Conaghan PG, Fleischmann R, Hsia EC, Xu W, et al. Significant improvement in synovitis, osteitis, and bone erosion following golimumab and methotrexate combination therapy as compared with methotrexate alone: a magnetic resonance imaging study of 318 methotrexate-naive rheumatoid arthritis patients. Arthritis. Rheumatism. 2011;63(12):3712–22.CrossRef
15.
go back to reference Conaghan PG, Peterfy C, Olech E, Kaine J, Ridley D, Dicarlo J, et al. The effects of tocilizumab on osteitis, synovitis and erosion progression in rheumatoid arthritis: results from the ACT-RAY MRI substudy. Annals of the Rheumatic Diseases. 2014;73(5):810–6.CrossRefPubMedPubMedCentral Conaghan PG, Peterfy C, Olech E, Kaine J, Ridley D, Dicarlo J, et al. The effects of tocilizumab on osteitis, synovitis and erosion progression in rheumatoid arthritis: results from the ACT-RAY MRI substudy. Annals of the Rheumatic Diseases. 2014;73(5):810–6.CrossRefPubMedPubMedCentral
16.
go back to reference Emery P, van der Heijde D, Ostergaard M, Conaghan PG, Genovese MC, Keystone EC, et al. Exploratory analyses of the association of MRI with clinical, laboratory and radiographic findings in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases. 2011;70(12):2126–30.CrossRefPubMedPubMedCentral Emery P, van der Heijde D, Ostergaard M, Conaghan PG, Genovese MC, Keystone EC, et al. Exploratory analyses of the association of MRI with clinical, laboratory and radiographic findings in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases. 2011;70(12):2126–30.CrossRefPubMedPubMedCentral
17.
go back to reference McQueen FM, Clarke A, McHaffie A, Reeves Q, Williams M, Robinson E, et al. Assessment of cartilage loss at the wrist in rheumatoid arthritis using a new MRI scoring system. Annals of the Rheumatic Diseases. 2010;69:1971–5.CrossRefPubMed McQueen FM, Clarke A, McHaffie A, Reeves Q, Williams M, Robinson E, et al. Assessment of cartilage loss at the wrist in rheumatoid arthritis using a new MRI scoring system. Annals of the Rheumatic Diseases. 2010;69:1971–5.CrossRefPubMed
18.
go back to reference van der Heijde DM, van Riel PL, Nuver-Zwart IH, Gribnau FW. vad de Putte LB. Effects of hydroxychloroquine and sulphasalazine on progression of joint damage in rheumatoid arthritis. Lancet. 1989;1(8646):1036–8.CrossRefPubMed van der Heijde DM, van Riel PL, Nuver-Zwart IH, Gribnau FW. vad de Putte LB. Effects of hydroxychloroquine and sulphasalazine on progression of joint damage in rheumatoid arthritis. Lancet. 1989;1(8646):1036–8.CrossRefPubMed
19.
go back to reference Porter D, Dale J, Sattar N. How low to aim in rheumatoid arthritis? Learning from other disciplines. Annals of the Rheumatic Diseases. 2014;73(3):480–2.CrossRefPubMed Porter D, Dale J, Sattar N. How low to aim in rheumatoid arthritis? Learning from other disciplines. Annals of the Rheumatic Diseases. 2014;73(3):480–2.CrossRefPubMed
20.
go back to reference Baker JF, Ostergaard M, Emery P, Hsia EC, Lu J, Baker DG, et al. Early MRI measures independently predict 1-year and 2-year radiographic progression in rheumatoid arthritis: secondary analysis from a large clinical trial. Annals of the Rheumatic Diseases. 2014;73(11):1968–74.CrossRefPubMed Baker JF, Ostergaard M, Emery P, Hsia EC, Lu J, Baker DG, et al. Early MRI measures independently predict 1-year and 2-year radiographic progression in rheumatoid arthritis: secondary analysis from a large clinical trial. Annals of the Rheumatic Diseases. 2014;73(11):1968–74.CrossRefPubMed
21.
go back to reference Nieuwenhuis WP, Mangnus L, van Steenbergen HW, Newsum EC, Huizinga TW, Reijnierse M, et al. Older age is associated with more MRI-detected inflammation in hand and foot joints. Rheumatology (Oxford). 2016;55(12):2212–9.CrossRefPubMed Nieuwenhuis WP, Mangnus L, van Steenbergen HW, Newsum EC, Huizinga TW, Reijnierse M, et al. Older age is associated with more MRI-detected inflammation in hand and foot joints. Rheumatology (Oxford). 2016;55(12):2212–9.CrossRefPubMed
22.
go back to reference Lindsay K, Ibrahim G, Sokoll K, Tripathi M, Melsom RD, PS H. The composite DAS Score is impractical to use in daily practice: evidence that physicians use the objective component of the DAS in decision making. Journal of clinical rheumatology. 2009;15(5):223–5.CrossRefPubMed Lindsay K, Ibrahim G, Sokoll K, Tripathi M, Melsom RD, PS H. The composite DAS Score is impractical to use in daily practice: evidence that physicians use the objective component of the DAS in decision making. Journal of clinical rheumatology. 2009;15(5):223–5.CrossRefPubMed
23.
go back to reference Glinatsi D, Baker JF, Hetland ML, Horslev-Petersen K, Ejbjerg BJ, Stengaard-Pedersen K, et al. Magnetic resonance imaging assessed inflammation in the wrist is associated with patient-reported physical impairment, global assessment of disease activity and pain in early rheumatoid arthritis: longitudinal results from two randomised controlled trials. Annals of the Rheumatic Diseases. 2017;76(10):1707–15.CrossRefPubMed Glinatsi D, Baker JF, Hetland ML, Horslev-Petersen K, Ejbjerg BJ, Stengaard-Pedersen K, et al. Magnetic resonance imaging assessed inflammation in the wrist is associated with patient-reported physical impairment, global assessment of disease activity and pain in early rheumatoid arthritis: longitudinal results from two randomised controlled trials. Annals of the Rheumatic Diseases. 2017;76(10):1707–15.CrossRefPubMed
24.
go back to reference Molenaar ET, Voskuyl AE, Dinant HJ, Bezemer PD, Boers M, Dijkmans BA. Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission. Arthritis & Rheumatism. 2004;50(1):36–42.CrossRef Molenaar ET, Voskuyl AE, Dinant HJ, Bezemer PD, Boers M, Dijkmans BA. Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission. Arthritis & Rheumatism. 2004;50(1):36–42.CrossRef
25.
go back to reference O’Dell JR, Mikuls TR, Taylor TH, Ahluwalia V, Brophy M, Warren SR, et al. Therapies for active rheumatoid arthritis after methotrexate failure. N Engl J Med. 2013;369(4):307–18.CrossRefPubMed O’Dell JR, Mikuls TR, Taylor TH, Ahluwalia V, Brophy M, Warren SR, et al. Therapies for active rheumatoid arthritis after methotrexate failure. N Engl J Med. 2013;369(4):307–18.CrossRefPubMed
26.
go back to reference Steunebrink LM, Vonkeman HE, ten Klooster PM, Hoekstra M, van Riel PL, van de Laar MA. Recently diagnosed rheumatoid arthritis patients benefit from a treat-to-target strategy: results from the DREAM registry. Clin Rheumatol. 2016;35(3):609–15.CrossRefPubMedPubMedCentral Steunebrink LM, Vonkeman HE, ten Klooster PM, Hoekstra M, van Riel PL, van de Laar MA. Recently diagnosed rheumatoid arthritis patients benefit from a treat-to-target strategy: results from the DREAM registry. Clin Rheumatol. 2016;35(3):609–15.CrossRefPubMedPubMedCentral
27.
go back to reference Gandjbakhch F, Haavardsholm EA, Conaghan PG, Ejbjerg B, Foltz V, Brown AK, et al. Determining a magnetic resonance imaging inflammatory activity acceptable state without subsequent radiographic progression in rheumatoid arthritis: results from a followup MRI study of 254 patients in clinical remission or low disease activity. J Rheumatol. 2014;41(2):398–406.CrossRefPubMed Gandjbakhch F, Haavardsholm EA, Conaghan PG, Ejbjerg B, Foltz V, Brown AK, et al. Determining a magnetic resonance imaging inflammatory activity acceptable state without subsequent radiographic progression in rheumatoid arthritis: results from a followup MRI study of 254 patients in clinical remission or low disease activity. J Rheumatol. 2014;41(2):398–406.CrossRefPubMed
28.
go back to reference Mandl P, Kurucz R, Niedermayer D, Balint PV, Smolen JS. Contributions of ultrasound beyond clinical data in assessing inflammatory disease activity in rheumatoid arthritis: current insights and future prospects. Rheumatology (Oxford). 2014;53(12):2136–42.CrossRefPubMed Mandl P, Kurucz R, Niedermayer D, Balint PV, Smolen JS. Contributions of ultrasound beyond clinical data in assessing inflammatory disease activity in rheumatoid arthritis: current insights and future prospects. Rheumatology (Oxford). 2014;53(12):2136–42.CrossRefPubMed
29.
go back to reference Haavardsholm EA, Aga AB, Olsen IC, Lillegraven S, Hammer HB, Uhlig T, et al. Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial. Bmj. 2016;i4205:354. Haavardsholm EA, Aga AB, Olsen IC, Lillegraven S, Hammer HB, Uhlig T, et al. Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial. Bmj. 2016;i4205:354.
30.
go back to reference Dale J, Stirling A, Zhang R, Purves D, Foley J, Sambrook M, et al. Targeting ultrasound remission in early rheumatoid arthritis: the results of the TaSER study, a randomised clinical trial. Annals of the Rheumatic Diseases. 2016;75(6):1043–50.CrossRefPubMed Dale J, Stirling A, Zhang R, Purves D, Foley J, Sambrook M, et al. Targeting ultrasound remission in early rheumatoid arthritis: the results of the TaSER study, a randomised clinical trial. Annals of the Rheumatic Diseases. 2016;75(6):1043–50.CrossRefPubMed
31.
go back to reference Hyrich KL, Watson KD, Silman AJ, Symmons DP. British Society for Rheumatology Biologics R. Predictors of response to anti-TNF-alpha therapy among patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford). 2006;45(12):1558–65.CrossRefPubMed Hyrich KL, Watson KD, Silman AJ, Symmons DP. British Society for Rheumatology Biologics R. Predictors of response to anti-TNF-alpha therapy among patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford). 2006;45(12):1558–65.CrossRefPubMed
Metadata
Title
Changes in clinical disease activity are weakly linked to changes in MRI inflammation on treat-to-target escalation of therapy in rheumatoid arthritis
Authors
Fiona M. McQueen
Peter Chapman
Terina Pollock
Dena D’Souza
Arier C. Lee
Nicola Dalbeth
Lisa Stamp
Karen Lindsay
Anthony Doyle
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2017
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-017-1433-7

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