Prognostic Markers of Radiographic Progression in Early Rheumatoid Arthritis

Jörg J. Goronzy, Eric Lawrence Matteson, James W. Fulbright, Kenneth J Warrington, April Chang-Miller, Gene G. Hunder, Thomas Mason, Audrey M. Nelson, Robert M. Valente, Cynthia Crowson, Henry A. Erlich, Rebecca L. Reynolds, Ronald G. Swee, W. Michael O'Fallon, Cornelia M. Weyand

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Objective. To identify prognostic markers that are predictive of progressive erosive disease in patients with early rheumatoid arthritis (RA). Methods. The study involved an inception cohort of 111 consecutive patients with RA and a disease duration of <1 year. Patients were treated according to an algorithm designed to avoid overtreatment of mild disease and to accelerate treatment in patients who had continuous disease activity. Patients were evaluated for the presence of clinical and laboratory disease activity markers. We determined the frequency of CD4+, CD28null T cells by flow cytometry, HLA-DRB1 gene polymorphisms by polymerase chain reaction (PCR)/sequencing, and 26 single-nucleotide polymorphisms in 19 candidate genes by multiplex PCR and hybridization to an immobilized probe array. Data were analyzed using proportional odds models to identify prognostic markers predictive of erosive progression over 2 years on serial hand/wrist radiographs. Results. After 2 years, disease activity in 52% of the cohort was controlled by treatment with hydroxychloroquine and nonsteroidal agents. Forty-eight percent of the patients did not develop erosions. Older age, presence of erosions at baseline, presence of rheumatoid factor, rheumatoid factor titer, and HLA-DRB1*04 alleles, particularly homozygosity for HLA-DRB1*04, were univariate predictors of radiographic progression. Promising novel markers were the frequency of CD4+, CD28null T cells as an immunosenescence indicator, and a polymorphism in the uteroglobin gene. Conclusion. Clinical disease activity in patients with early RA can frequently be controlled with nonaggressive treatment, but this is not always sufficient to prevent new erosions. Rheumatoid factor titer, HLA-DRB1 polymorphisms, age, and immunosenescence markers are predictors of poor radiographic outcome. A polymorphism in the uteroglobin gene may identify patients who have a low risk of erosive disease.

Original languageEnglish (US)
Pages (from-to)43-54
Number of pages12
JournalArthritis and Rheumatism
Volume50
Issue number1
DOIs
StatePublished - Jan 2004

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Rheumatoid Arthritis
Rheumatoid Factor
Uteroglobin
HLA-DRB1 Chains
Genes
Hydroxychloroquine
T-Lymphocytes
Multiplex Polymerase Chain Reaction
Wrist
Single Nucleotide Polymorphism
Flow Cytometry
Therapeutics
Hand
Alleles
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

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Prognostic Markers of Radiographic Progression in Early Rheumatoid Arthritis. / Goronzy, Jörg J.; Matteson, Eric Lawrence; Fulbright, James W.; Warrington, Kenneth J; Chang-Miller, April; Hunder, Gene G.; Mason, Thomas; Nelson, Audrey M.; Valente, Robert M.; Crowson, Cynthia; Erlich, Henry A.; Reynolds, Rebecca L.; Swee, Ronald G.; O'Fallon, W. Michael; Weyand, Cornelia M.

In: Arthritis and Rheumatism, Vol. 50, No. 1, 01.2004, p. 43-54.

Research output: Contribution to journalArticle

Goronzy, JJ, Matteson, EL, Fulbright, JW, Warrington, KJ, Chang-Miller, A, Hunder, GG, Mason, T, Nelson, AM, Valente, RM, Crowson, C, Erlich, HA, Reynolds, RL, Swee, RG, O'Fallon, WM & Weyand, CM 2004, 'Prognostic Markers of Radiographic Progression in Early Rheumatoid Arthritis', Arthritis and Rheumatism, vol. 50, no. 1, pp. 43-54. https://doi.org/10.1002/art.11445
Goronzy, Jörg J. ; Matteson, Eric Lawrence ; Fulbright, James W. ; Warrington, Kenneth J ; Chang-Miller, April ; Hunder, Gene G. ; Mason, Thomas ; Nelson, Audrey M. ; Valente, Robert M. ; Crowson, Cynthia ; Erlich, Henry A. ; Reynolds, Rebecca L. ; Swee, Ronald G. ; O'Fallon, W. Michael ; Weyand, Cornelia M. / Prognostic Markers of Radiographic Progression in Early Rheumatoid Arthritis. In: Arthritis and Rheumatism. 2004 ; Vol. 50, No. 1. pp. 43-54.
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AU - Goronzy, Jörg J.

AU - Matteson, Eric Lawrence

AU - Fulbright, James W.

AU - Warrington, Kenneth J

AU - Chang-Miller, April

AU - Hunder, Gene G.

AU - Mason, Thomas

AU - Nelson, Audrey M.

AU - Valente, Robert M.

AU - Crowson, Cynthia

AU - Erlich, Henry A.

AU - Reynolds, Rebecca L.

AU - Swee, Ronald G.

AU - O'Fallon, W. Michael

AU - Weyand, Cornelia M.

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N2 - Objective. To identify prognostic markers that are predictive of progressive erosive disease in patients with early rheumatoid arthritis (RA). Methods. The study involved an inception cohort of 111 consecutive patients with RA and a disease duration of <1 year. Patients were treated according to an algorithm designed to avoid overtreatment of mild disease and to accelerate treatment in patients who had continuous disease activity. Patients were evaluated for the presence of clinical and laboratory disease activity markers. We determined the frequency of CD4+, CD28null T cells by flow cytometry, HLA-DRB1 gene polymorphisms by polymerase chain reaction (PCR)/sequencing, and 26 single-nucleotide polymorphisms in 19 candidate genes by multiplex PCR and hybridization to an immobilized probe array. Data were analyzed using proportional odds models to identify prognostic markers predictive of erosive progression over 2 years on serial hand/wrist radiographs. Results. After 2 years, disease activity in 52% of the cohort was controlled by treatment with hydroxychloroquine and nonsteroidal agents. Forty-eight percent of the patients did not develop erosions. Older age, presence of erosions at baseline, presence of rheumatoid factor, rheumatoid factor titer, and HLA-DRB1*04 alleles, particularly homozygosity for HLA-DRB1*04, were univariate predictors of radiographic progression. Promising novel markers were the frequency of CD4+, CD28null T cells as an immunosenescence indicator, and a polymorphism in the uteroglobin gene. Conclusion. Clinical disease activity in patients with early RA can frequently be controlled with nonaggressive treatment, but this is not always sufficient to prevent new erosions. Rheumatoid factor titer, HLA-DRB1 polymorphisms, age, and immunosenescence markers are predictors of poor radiographic outcome. A polymorphism in the uteroglobin gene may identify patients who have a low risk of erosive disease.

AB - Objective. To identify prognostic markers that are predictive of progressive erosive disease in patients with early rheumatoid arthritis (RA). Methods. The study involved an inception cohort of 111 consecutive patients with RA and a disease duration of <1 year. Patients were treated according to an algorithm designed to avoid overtreatment of mild disease and to accelerate treatment in patients who had continuous disease activity. Patients were evaluated for the presence of clinical and laboratory disease activity markers. We determined the frequency of CD4+, CD28null T cells by flow cytometry, HLA-DRB1 gene polymorphisms by polymerase chain reaction (PCR)/sequencing, and 26 single-nucleotide polymorphisms in 19 candidate genes by multiplex PCR and hybridization to an immobilized probe array. Data were analyzed using proportional odds models to identify prognostic markers predictive of erosive progression over 2 years on serial hand/wrist radiographs. Results. After 2 years, disease activity in 52% of the cohort was controlled by treatment with hydroxychloroquine and nonsteroidal agents. Forty-eight percent of the patients did not develop erosions. Older age, presence of erosions at baseline, presence of rheumatoid factor, rheumatoid factor titer, and HLA-DRB1*04 alleles, particularly homozygosity for HLA-DRB1*04, were univariate predictors of radiographic progression. Promising novel markers were the frequency of CD4+, CD28null T cells as an immunosenescence indicator, and a polymorphism in the uteroglobin gene. Conclusion. Clinical disease activity in patients with early RA can frequently be controlled with nonaggressive treatment, but this is not always sufficient to prevent new erosions. Rheumatoid factor titer, HLA-DRB1 polymorphisms, age, and immunosenescence markers are predictors of poor radiographic outcome. A polymorphism in the uteroglobin gene may identify patients who have a low risk of erosive disease.

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