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Predictors for the Progression of Cervical Lesion in Rheumatoid Arthritis Under the Treatment of Biological Agents

Kaito, Takashi MD*; Ohshima, Shirou MD; Fujiwara, Hiroyasu MD; Makino, Takahiro MD*; Yonenobu, Kazuo MD§

doi: 10.1097/BRS.0000000000000066
Cervical Spine

Study Design. Retrospective cohort analysis.

Objective. To clarify the effect of biological agents (BAs) on the development and progression of cervical lesions in patients with rheumatoid arthritis (RA) and to identify biomarkers that accurately predict disease progression.

Summary of Background Data. The introduction of BAs changed the paradigm of RA treatment. However, their effects on cervical lesions in patients with RA have not been studied.

Methods. Ninety-one subjects who had received BAs for 2 years or more were enrolled. Mean radiographical interval was 3.9 years. Disease activity was evaluated by disease activity score–C-reactive protein levels, and matrix metalloproteinase-3 levels. Cervical lesions were defined as an atlantodental interval more than 3 mm for atlantoaxial subluxation (AAS), Ranawat value less than 13 mm for vertical subluxation (VS), and anterior or posterior listhesis more than 2 mm for subaxial subluxation. Disease progression was defined radiographically as an increase in the atlantodental interval more than 2 mm for AAS, a decrease in both Ranawat and Redlund-Johnell values more than 2 mm for VS, and an increase in listhesis more than 2 mm for subaxial subluxation. We used multivariate regression techniques to assess predictors of disease progression.

Results. Baseline radiographical evaluation showed no pre-existing cervical lesion in 44 patients, AAS in 29, and VS in 18. Radiological progression occurred in 7% patients without baseline lesions, 79% in the AAS group, and 72% in the VS group. The incidence of progression was significantly lower in patients without lesions at baseline. Multivariate regression analysis demonstrated pre-existing cervical lesions, disease activity score–C-reactive protein levels at baseline and metalloproteinase-3 levels at final visit as good predictors of RA progression.

Conclusion. BAs prevented de novo cervical lesions in patients with RA but failed to control progression in patients with pre-existing cervical lesions. Disease activity score–C-reactive protein levels at baseline were related to pre-existing joint destruction, and metalloproteinase-3 levels accurately predicted ongoing bone destruction during BA treatment.

Level of Evidence: 3

Ninety-one cases of patients with rheumatoid arthritis who had been receiving biological agent treatment for more than 2 years were reviewed to determine predictors of progression of cervical spine lesions. Pre-existing cervical lesions, baseline disease activity score–C-reactive protein values, and metalloproteinase-3 levels were predictors of disease progression.

*Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan; Departments of

Rheumatology; and

Orthopaedic Surgery, National Hospital Organization Osaka Minami Medical Center, Osaka, Japan; and

§Graduate School of Health Care Sciences, Jikei Institute, Osaka, Japan.

Address correspondence and reprint requests to Takashi Kaito, MD, Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; E-mail:

Acknowledgment date: July 31, 2013. First revision date: September 5, 2013. Second revision date: September 21, 2013. Acceptance date: September 25, 2013.

The device(s)/drug(s) is/are FDA-approved or approved by corresponding national agency for this indication.

The Japan Orthopaedics and Traumatology Foundation, Inc. No. 260 grant funds were received in support of this work.

No relevant financial activities outside the submitted work.

© 2013 by Lippincott Williams & Wilkins