STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To examine factors related to severe aggravation of preexisting cervical lesions in patients with rheumatoid arthritis (RA) under current pharmacologic treatments with biologics. SUMMARY OF BACKGROUND DATA: Advanced RA cervical lesions carry a risk of irreversible damage to the spinal cord; however, risk factors for aggravation are unclear after the use of biologics became more popular. METHODS: Of 166 patients with preexisting cervical lesions at baseline, 87 who had cervical X-ray images taken at baseline and at the final visit (with an interval of more than 1 yr) were evaluated retrospectively. Aggravated instabilities determined at the final visit, were defined as follows: atlantoaxial subluxation (AAS) = atlantodental interval ≧ 10 mm; vertebral subluxation (VS) = a Ranawat value < 10 mm; and subaxial subluxation (SAS) = an anterior vertebral slip ≧ 4 mm or a multilevel slip ≧ 2 mm. Patients were divided into two groups based on the radiographic results: severe aggravation and non-severe aggravation. Explanatory variables were gender, age of RA onset, duration of disease, average observation period, Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) at baseline, drug treatment history, presence of mutilating deformities in the hands, presence of RA-related joint surgery, and the prevalence of each cervical lesion at baseline. RESULTS: The severe group comprised 14 patients (16.1%). There was no significant difference between the two groups with respect to demographic data. Multivariate logistic regression analysis revealed that preexisting SAS lesions (odds ratio: 7.59, 95% confidence interval: 1.16-49.6) and no history of biologic treatment (odds ratio, 0.10; 95% confidence interval, 0.17-0.58) were associated with aggravation. CONCLUSION: Preexisting SAS lesions were associated with aggravation. Meanwhile, biologics may be effective at preventing aggravation.Level of Evidence: 3.