Accelerated development of cervical spine instabilities in rheumatoid arthritis: A prospective minimum 5-year cohort study

Objective: To clarify the incidence and predictive risk factors of cervical spine instabilities which may induce compression myelopathy in patients with rheumatoid arthritis (RA). Methods: Three types of cervical spine instability were radiographically categorized into "moderate" and "severe" based on atlantoaxial subluxation (AAS: atlantodental interval >3 mm versus ≥10 mm), vertical subluxation (VS: Ranawat value, 13 mm versus ≤10 mm), and subaxial subluxation (SAS: irreducible translation ≥2 mm versus ≥4 mm or at multiple). 228 "definite" or "classical" RA patients (140 without instability and 88 with "moderate" instability) were prospectively followed for >5 years. The endpoint incidence of "severe" instabilities and predictors for "severe" instability were determined. Results: Patients with baseline "moderate" instability, including all sub-groups (AAS⁺ [VS^- SAS^-], VS⁺ [SAS^- AAS ^±], and SAS⁺ [AAS^± VS ^±]), developed "severe" instabilities more frequently (33.3% with AAS⁺, 75.0% with VS⁺, and 42.9% with SAS⁺) than those initially without instability (12.9%; p<0.003, p<0.003, and p = 0.061, respectively). The incidence of cervical canal stenosis and/or basilar invagination was also higher in patients with initial instability (17.5% with AAS⁺, 37.5% with VS⁺, and 14.3% with SAS⁺) than in those without instability (7.1%; p = 0.028, p<0.003, and p = 0.427, respectively). Multivariable logistic regression analysis identified corticosteroid administration, Steinbrocker stage III or IV at baseline, mutilating changes at baseline, and the development of mutilans during the follow-up period correlated with the progression to "severe" instability (p<0.05). Conclusions: This prospective cohort study demonstrates accelerated development of cervical spine involvement in RA patients with pre-existing instability - especially VS. Advanced peripheral erosiveness and concomitant corticosteroid treatment are indicators for poor prognosis of the cervical spine in RA.