Methods: All subjects who were enrolled in a 24-week double-blind randomized clinical trial comparing etanercept and placebo were eligible to participate in an open-label, long-term extension study. All patients used etanercept (25 mg twice weekly) between 24 weeks and 2 years. X-rays of the cervical spine and lumbar spine were obtained at baseline of the initial trial and after 2 years. X-rays from subjects in the Outcome in AS International Study (OASIS) from baseline and 2-year follow-up were used as a comparator. Two independent readers, blinded to image origin and sequence, scored these images using the modified Stoke AS Spinal Score (mSASSS).

Results: A total of 257 subjects received at least 1 dose of investigational product in the etanercept trials and had a baseline x-ray film, and were compared with 175 subjects in OASIS with x-rays at baseline and without total spinal fusion. Mean change from baseline in mSASSS scores (SD) was 0.91 (2.45) for subjects in the etanercept trials, compared with 0.95 (3.18) for all subjects in OASIS (p = 0.996), and 1.27 (3.64) for subjects in OASIS who qualified for enrollment in the etanercept trials (p = 0.5606).

Conclusion: Whereas clinical findings demonstrate sustained, durable benefits with long-term etanercept therapy in patients with AS, x-ray evaluations suggest that progression of structural damage continued. Adjustment for baseline damage and disease activity did not change the results. The primary clinical benefit in the initial 2 years of TNF antagonism may therefore be related to suppression of inflammatory processes, rather than inhibition of structural progression. The effect of etanercept treatment beyond 2 years on progression of structural damage warrants further study.