A retrospective cohort study. To examine factors related to severe aggravation of preexisting cervical lesions in patients with rheumatoid arthritis (RA) under current pharmacologic treatments with biologics. 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. 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. 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. Preexisting SAS lesions were associated with aggravation. Meanwhile, biologics may be effective at preventing aggravation.Level of Evidence: 3.