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A 5-year prospective cohort study of cervical spine instabilities in rheumatoid arthritis (RA).To clarify the natural course of cervical instabilities in RA patients and to determine predictors for the prognosis of RA cervical spine.Although several previous studies investigating the natural history of RA cervical spine have been reported, few of them have described radiological predictive factors for the aggravation of these instabilities.Two hundred sixty-seven outpatients with “definite” or “classical” RA initially assigned were prospectively followed for over 5 years. Radiographic cervical findings were classified into three representative instabilities: atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial subluxation (SAS). The aggravations of these instabilities were identified in the cases with a decrease of at least 2 mm in the Ranawat value of VS, an increase of at least 1 mm in translation of SAS, or a new development of respective instabilities. RA stages and mutilating changes were assessed in the hand radiograms.Fifty-two point four percent of 267 patients, without any cervical instability at the beginning of follow-up, decreased to 29.6% at the end (P < 0.01), whereas VS and SAS increased significantly (P < 0.01). The aggravation of VS was observed at statistically higher rates in patients with pre-existing instabilities as follows; 25.7% of AAS (P = 0.01), 49.1% of VS (P < 0.01), and 41.2% of SAS (P = 0.06). The aggravation of SAS was also detected in 47.2% of VS and 64.7% of SAS (P < 0.01). Patients with pre-existing mutilating changes exhibited the aggravations of VS and SAS in significantly higher incidences (P < 0.01). Furthermore, the cases with development into mutilating changes during the follow-up showed significantly higher tendencies for the aggravations of these instabilities (P < 0.01).The incidences of VS and SAS significantly increased during the minimum 5-year follow-up. Prognostic factors of these instabilities were revealed to be the initial radiological findings of VS, SAS, and mutilating changes.