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Research ArticleArticle

Early Local Swelling and Tenderness Are Associated with Large-joint Damage After 8 Years of Treatment to Target in Patients with Recent-onset Rheumatoid Arthritis

Marianne van den Broek, Linda Dirven, Herman M. Kroon, Margreet Kloppenburg, H. Karel Ronday, André J. Peeters, Pit J.S.M. Kerstens, Tom W.J. Huizinga, Willem F. Lems and Cornelia F. Allaart
The Journal of Rheumatology April 2013, jrheum.121248; DOI: https://doi.org/10.3899/jrheum.121248
Marianne van den Broek
From the Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden; Department of Radiology, LUMC, Leiden; Department of Rheumatology, Haga Hospital, The Hague; Department of Rheumatology, Reinier de Graaf Gasthuis, Delft; Department of Rheumatology, Jan van Breemen Research Institute, Reade, Amsterdam; and Department of Rheumatology, VU Medical Center, Amsterdam, The Netherlands. Supported by the Dutch College of Health Insurance Companies, Janssen B.V., and Schering-Plough Ltd. M. van den Broek, MD; L. Dirven, PhD, Department of Rheumatology, LUMC; H.M. Kroon, MD, PhD, Department of Radiology, LUMC; M. Kloppenburg, MD, PhD, Department of Rheumatology, LUMC; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; A.J. Peeters, MD, PhD, Department of Rheumatology, Reinier de Graaf Gasthuis; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; T.W.J. Huizinga, MD, PhD, Department of Rheumatology, LUMC; W.F. Lems, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; Department of Rheumatology, VU Medical Center; C.F. Allaart, MD, PhD, Department of Rheumatology, LUMC. M. van den Broek and L. Dirven contributed equally to this report. Address correspondence to Dr. M. van den Broek, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: m.van_den_broek{at}lumc.nl Accepted for publication January 25, 2013.
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Linda Dirven
From the Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden; Department of Radiology, LUMC, Leiden; Department of Rheumatology, Haga Hospital, The Hague; Department of Rheumatology, Reinier de Graaf Gasthuis, Delft; Department of Rheumatology, Jan van Breemen Research Institute, Reade, Amsterdam; and Department of Rheumatology, VU Medical Center, Amsterdam, The Netherlands. Supported by the Dutch College of Health Insurance Companies, Janssen B.V., and Schering-Plough Ltd. M. van den Broek, MD; L. Dirven, PhD, Department of Rheumatology, LUMC; H.M. Kroon, MD, PhD, Department of Radiology, LUMC; M. Kloppenburg, MD, PhD, Department of Rheumatology, LUMC; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; A.J. Peeters, MD, PhD, Department of Rheumatology, Reinier de Graaf Gasthuis; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; T.W.J. Huizinga, MD, PhD, Department of Rheumatology, LUMC; W.F. Lems, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; Department of Rheumatology, VU Medical Center; C.F. Allaart, MD, PhD, Department of Rheumatology, LUMC. M. van den Broek and L. Dirven contributed equally to this report. Address correspondence to Dr. M. van den Broek, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: m.van_den_broek{at}lumc.nl Accepted for publication January 25, 2013.
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Herman M. Kroon
From the Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden; Department of Radiology, LUMC, Leiden; Department of Rheumatology, Haga Hospital, The Hague; Department of Rheumatology, Reinier de Graaf Gasthuis, Delft; Department of Rheumatology, Jan van Breemen Research Institute, Reade, Amsterdam; and Department of Rheumatology, VU Medical Center, Amsterdam, The Netherlands. Supported by the Dutch College of Health Insurance Companies, Janssen B.V., and Schering-Plough Ltd. M. van den Broek, MD; L. Dirven, PhD, Department of Rheumatology, LUMC; H.M. Kroon, MD, PhD, Department of Radiology, LUMC; M. Kloppenburg, MD, PhD, Department of Rheumatology, LUMC; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; A.J. Peeters, MD, PhD, Department of Rheumatology, Reinier de Graaf Gasthuis; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; T.W.J. Huizinga, MD, PhD, Department of Rheumatology, LUMC; W.F. Lems, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; Department of Rheumatology, VU Medical Center; C.F. Allaart, MD, PhD, Department of Rheumatology, LUMC. M. van den Broek and L. Dirven contributed equally to this report. Address correspondence to Dr. M. van den Broek, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: m.van_den_broek{at}lumc.nl Accepted for publication January 25, 2013.
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Margreet Kloppenburg
From the Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden; Department of Radiology, LUMC, Leiden; Department of Rheumatology, Haga Hospital, The Hague; Department of Rheumatology, Reinier de Graaf Gasthuis, Delft; Department of Rheumatology, Jan van Breemen Research Institute, Reade, Amsterdam; and Department of Rheumatology, VU Medical Center, Amsterdam, The Netherlands. Supported by the Dutch College of Health Insurance Companies, Janssen B.V., and Schering-Plough Ltd. M. van den Broek, MD; L. Dirven, PhD, Department of Rheumatology, LUMC; H.M. Kroon, MD, PhD, Department of Radiology, LUMC; M. Kloppenburg, MD, PhD, Department of Rheumatology, LUMC; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; A.J. Peeters, MD, PhD, Department of Rheumatology, Reinier de Graaf Gasthuis; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; T.W.J. Huizinga, MD, PhD, Department of Rheumatology, LUMC; W.F. Lems, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; Department of Rheumatology, VU Medical Center; C.F. Allaart, MD, PhD, Department of Rheumatology, LUMC. M. van den Broek and L. Dirven contributed equally to this report. Address correspondence to Dr. M. van den Broek, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: m.van_den_broek{at}lumc.nl Accepted for publication January 25, 2013.
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H. Karel Ronday
From the Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden; Department of Radiology, LUMC, Leiden; Department of Rheumatology, Haga Hospital, The Hague; Department of Rheumatology, Reinier de Graaf Gasthuis, Delft; Department of Rheumatology, Jan van Breemen Research Institute, Reade, Amsterdam; and Department of Rheumatology, VU Medical Center, Amsterdam, The Netherlands. Supported by the Dutch College of Health Insurance Companies, Janssen B.V., and Schering-Plough Ltd. M. van den Broek, MD; L. Dirven, PhD, Department of Rheumatology, LUMC; H.M. Kroon, MD, PhD, Department of Radiology, LUMC; M. Kloppenburg, MD, PhD, Department of Rheumatology, LUMC; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; A.J. Peeters, MD, PhD, Department of Rheumatology, Reinier de Graaf Gasthuis; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; T.W.J. Huizinga, MD, PhD, Department of Rheumatology, LUMC; W.F. Lems, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; Department of Rheumatology, VU Medical Center; C.F. Allaart, MD, PhD, Department of Rheumatology, LUMC. M. van den Broek and L. Dirven contributed equally to this report. Address correspondence to Dr. M. van den Broek, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: m.van_den_broek{at}lumc.nl Accepted for publication January 25, 2013.
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André J. Peeters
From the Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden; Department of Radiology, LUMC, Leiden; Department of Rheumatology, Haga Hospital, The Hague; Department of Rheumatology, Reinier de Graaf Gasthuis, Delft; Department of Rheumatology, Jan van Breemen Research Institute, Reade, Amsterdam; and Department of Rheumatology, VU Medical Center, Amsterdam, The Netherlands. Supported by the Dutch College of Health Insurance Companies, Janssen B.V., and Schering-Plough Ltd. M. van den Broek, MD; L. Dirven, PhD, Department of Rheumatology, LUMC; H.M. Kroon, MD, PhD, Department of Radiology, LUMC; M. Kloppenburg, MD, PhD, Department of Rheumatology, LUMC; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; A.J. Peeters, MD, PhD, Department of Rheumatology, Reinier de Graaf Gasthuis; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; T.W.J. Huizinga, MD, PhD, Department of Rheumatology, LUMC; W.F. Lems, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; Department of Rheumatology, VU Medical Center; C.F. Allaart, MD, PhD, Department of Rheumatology, LUMC. M. van den Broek and L. Dirven contributed equally to this report. Address correspondence to Dr. M. van den Broek, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: m.van_den_broek{at}lumc.nl Accepted for publication January 25, 2013.
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Pit J.S.M. Kerstens
From the Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden; Department of Radiology, LUMC, Leiden; Department of Rheumatology, Haga Hospital, The Hague; Department of Rheumatology, Reinier de Graaf Gasthuis, Delft; Department of Rheumatology, Jan van Breemen Research Institute, Reade, Amsterdam; and Department of Rheumatology, VU Medical Center, Amsterdam, The Netherlands. Supported by the Dutch College of Health Insurance Companies, Janssen B.V., and Schering-Plough Ltd. M. van den Broek, MD; L. Dirven, PhD, Department of Rheumatology, LUMC; H.M. Kroon, MD, PhD, Department of Radiology, LUMC; M. Kloppenburg, MD, PhD, Department of Rheumatology, LUMC; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; A.J. Peeters, MD, PhD, Department of Rheumatology, Reinier de Graaf Gasthuis; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; T.W.J. Huizinga, MD, PhD, Department of Rheumatology, LUMC; W.F. Lems, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; Department of Rheumatology, VU Medical Center; C.F. Allaart, MD, PhD, Department of Rheumatology, LUMC. M. van den Broek and L. Dirven contributed equally to this report. Address correspondence to Dr. M. van den Broek, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: m.van_den_broek{at}lumc.nl Accepted for publication January 25, 2013.
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Tom W.J. Huizinga
From the Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden; Department of Radiology, LUMC, Leiden; Department of Rheumatology, Haga Hospital, The Hague; Department of Rheumatology, Reinier de Graaf Gasthuis, Delft; Department of Rheumatology, Jan van Breemen Research Institute, Reade, Amsterdam; and Department of Rheumatology, VU Medical Center, Amsterdam, The Netherlands. Supported by the Dutch College of Health Insurance Companies, Janssen B.V., and Schering-Plough Ltd. M. van den Broek, MD; L. Dirven, PhD, Department of Rheumatology, LUMC; H.M. Kroon, MD, PhD, Department of Radiology, LUMC; M. Kloppenburg, MD, PhD, Department of Rheumatology, LUMC; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; A.J. Peeters, MD, PhD, Department of Rheumatology, Reinier de Graaf Gasthuis; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; T.W.J. Huizinga, MD, PhD, Department of Rheumatology, LUMC; W.F. Lems, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; Department of Rheumatology, VU Medical Center; C.F. Allaart, MD, PhD, Department of Rheumatology, LUMC. M. van den Broek and L. Dirven contributed equally to this report. Address correspondence to Dr. M. van den Broek, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: m.van_den_broek{at}lumc.nl Accepted for publication January 25, 2013.
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Willem F. Lems
From the Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden; Department of Radiology, LUMC, Leiden; Department of Rheumatology, Haga Hospital, The Hague; Department of Rheumatology, Reinier de Graaf Gasthuis, Delft; Department of Rheumatology, Jan van Breemen Research Institute, Reade, Amsterdam; and Department of Rheumatology, VU Medical Center, Amsterdam, The Netherlands. Supported by the Dutch College of Health Insurance Companies, Janssen B.V., and Schering-Plough Ltd. M. van den Broek, MD; L. Dirven, PhD, Department of Rheumatology, LUMC; H.M. Kroon, MD, PhD, Department of Radiology, LUMC; M. Kloppenburg, MD, PhD, Department of Rheumatology, LUMC; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; A.J. Peeters, MD, PhD, Department of Rheumatology, Reinier de Graaf Gasthuis; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; T.W.J. Huizinga, MD, PhD, Department of Rheumatology, LUMC; W.F. Lems, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; Department of Rheumatology, VU Medical Center; C.F. Allaart, MD, PhD, Department of Rheumatology, LUMC. M. van den Broek and L. Dirven contributed equally to this report. Address correspondence to Dr. M. van den Broek, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: m.van_den_broek{at}lumc.nl Accepted for publication January 25, 2013.
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Cornelia F. Allaart
From the Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden; Department of Radiology, LUMC, Leiden; Department of Rheumatology, Haga Hospital, The Hague; Department of Rheumatology, Reinier de Graaf Gasthuis, Delft; Department of Rheumatology, Jan van Breemen Research Institute, Reade, Amsterdam; and Department of Rheumatology, VU Medical Center, Amsterdam, The Netherlands. Supported by the Dutch College of Health Insurance Companies, Janssen B.V., and Schering-Plough Ltd. M. van den Broek, MD; L. Dirven, PhD, Department of Rheumatology, LUMC; H.M. Kroon, MD, PhD, Department of Radiology, LUMC; M. Kloppenburg, MD, PhD, Department of Rheumatology, LUMC; H.K. Ronday, MD, PhD, Department of Rheumatology, Haga Hospital; A.J. Peeters, MD, PhD, Department of Rheumatology, Reinier de Graaf Gasthuis; P.J.S.M. Kerstens, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; T.W.J. Huizinga, MD, PhD, Department of Rheumatology, LUMC; W.F. Lems, MD, PhD, Department of Rheumatology, Jan van Breemen Research Institute, Reade; Department of Rheumatology, VU Medical Center; C.F. Allaart, MD, PhD, Department of Rheumatology, LUMC. M. van den Broek and L. Dirven contributed equally to this report. Address correspondence to Dr. M. van den Broek, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: m.van_den_broek{at}lumc.nl Accepted for publication January 25, 2013.
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Abstract

Objective To assess whether early swelling and tenderness in large joints in patients with rheumatoid arthritis (RA) is predictive of later local damage and whether this leads to functional disability.

Methods Two-year clinical and 8-year radiological followup data from the BeSt study (trial numbers NTR262 and NTR265), a randomized controlled treat-to-target trial, were used. The association between early local joint swelling and/or tenderness (at least once, or for ≥ 2 consecutive visits) and later large-joint damage (Larsen score ≥ 1) was assessed using generalized estimating equations. The association between large-joint damage and functional ability [by Health Assessment Questionnaire (HAQ)] was assessed using logistic and linear regression analysis.

Results Clinical and 8-year radiological data were available for 290 patients. Concomitant local joint swelling and tenderness at least once in the first 2 years was independently associated with damage of the large joints (OR 2.5, 95% CI 1.7–3.6), as was swelling without tenderness (OR 2.0, 95% CI 1.1–3.6). Stronger effects were seen for persistent swelling and/or tenderness. Other independent predictors for joint damage were baseline erythrocyte sedimentation rate (OR 1.01, 95% CI 1.01–1.02) and the presence of rheumatoid factor and/or anticitrullinated protein antibodies (OR 2.5, 95% CI 1.5–4.1; and OR 2.2, 95% CI 1.3–3.8, respectively). Patients with large-joint damage had a higher HAQ score after 8 years than patients without (difference 0.15).

Conclusion Early local swelling and tenderness are independent predictors of later joint damage in these joints after 8 years of Disease Activity Score-guided treatment in patients with RA. This suggests that suppression of local inflammation could help prevent local damage and functional disability.

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The Journal of Rheumatology: 53 (2)
The Journal of Rheumatology
Vol. 53, Issue 2
1 Feb 2026
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Early Local Swelling and Tenderness Are Associated with Large-joint Damage After 8 Years of Treatment to Target in Patients with Recent-onset Rheumatoid Arthritis
Marianne van den Broek, Linda Dirven, Herman M. Kroon, Margreet Kloppenburg, H. Karel Ronday, André J. Peeters, Pit J.S.M. Kerstens, Tom W.J. Huizinga, Willem F. Lems, Cornelia F. Allaart
The Journal of Rheumatology Apr 2013, jrheum.121248; DOI: 10.3899/jrheum.121248

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Early Local Swelling and Tenderness Are Associated with Large-joint Damage After 8 Years of Treatment to Target in Patients with Recent-onset Rheumatoid Arthritis
Marianne van den Broek, Linda Dirven, Herman M. Kroon, Margreet Kloppenburg, H. Karel Ronday, André J. Peeters, Pit J.S.M. Kerstens, Tom W.J. Huizinga, Willem F. Lems, Cornelia F. Allaart
The Journal of Rheumatology Apr 2013, jrheum.121248; DOI: 10.3899/jrheum.121248
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