Background Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that affects synovial joints. Cervical spine damage, due to rheumatoid inflammation, may produces atlantoaxial subluxation that can produce severe neurological symptoms. Early and aggressive treatment with disease-modifying anti-rheumatic drugs (DMARDs) has been shown to prevent cervical spine damage due to RA, but the effect of the biological therapy (BT) in this particular anatomical location, has not been well established.
Objectives To analyze the prevalence of the anterior atlantoaxoidal subluxation (AAS) in RA patients receiving biological therapies and to assess possible risk factors.
Methods X-Ray of 221 RA patients treated with at least one BT from December 1999 to December 2012 were analyzed. AAS was defined as an anterior atlantoaxoidal distance ≥3mm. All patients diagnosed of AAS prior to BT were excluded from this analysis and X-Ray from the remaining patients were reviewed at two Time points: before (T1) and after initiating the BT (T2). Epidemiological features (i.e. gender, age and age at diagnosis), clinical features (i.e. rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA) and erosions) and previous DMARDs were analyzed. Disease activity was established according to the index DAS28 at T2 radiographic control. The number of BT during the follow-up was also recorded.
A survival analysis of AAS was conducted according to two event models, namely (A) interval right-censored analysis , and (B) right-censored analysis with mid-point imputation where the time to AAS was approximately the half time between the BT starting date and the AAS positive X-Ray date. Univariate statistical analysis was performed using both the log rank test in models A and B and the Cox's proportional-hazards in model B. The latter was also used to perform the multivariate statistical analysis.
Results 58 (26%) patients were excluded from this analysis due to AAS prior BT. A total number of n=163 (74%) patients were analyzed. Of these, 89.5% were women, 73% had positive RF and 76% ACPA positive. Erosions were detected in 77% of patients. After BT initiation, AAS was observed in n=38 (23%) patients. The mean value of the period after starting BT and AAS diagnosis was 2.7 years. In the univariate analysis (i.e. Cox's test), it was found that RF positivity (P-value=8.56e-03), ACPA positivity (P-value=5.22e-03) and DAS28 (P-value=3.59e-03) were associated with AAS development.
In multivariate analysis only the presence of ACPA (P-value=8.57e-03) and elevated DAS28 (P-value=0.034) at the time of the X-Ray were associated with development of AAS. The duration of the disease was not significantly associated with the development of the AAS.
Conclusions In our series of RA patients, it has been observed that AAS development was present in a substantial subset of patients in spite of having started biological therapy. The main risk factors for AAS development in these subgroup of patients was the presence of ACPA antibodies and high disease activity measured by DAS28.
Henschel, Volkmar, Christiane HeiB, and Ulrich Mansmann. intcox: Compendium to apply the iterative convex minorant algorithm to interval censored event data. (2009).
Disclosure of Interest None declared