ADALIMUMAB IS EFFECTIVE IN REDUCING SIGNS AND SYMPTOMS IN ANKYLOSING SPONDYLITIS PATIENTS WITH TOTAL SPINAL ANKYLOSIS – RESULTS FROM ATLAS

Background: Total spinal ankylosis (TSA) represents end-stage fusion of the spine in patients (pts) with ankylosing spondylitis (AS). It is not uncommon for pts who already have TSA to still have symptoms of active disease. The Adalimumab Trial Evaluating Long-Term Efficacy and Safety in AS (ATLAS) is the only phase III, randomized, placebo (PBO)-controlled anti-TNF trial in AS that allowed the inclusion of pts with TSA.Objectives: To evaluate the long-term efficacy and safety of adalimumab in pts with TSA.Methods: ATLAS enrolled pts with active AS who had an inadequate response to at least 1 NSAID. Pts received either double-blind (DB) adalimumab 40 mg every other week (eow) or PBO for 24 weeks (wks). Efficacy was measured by the ASsessment in AS (ASAS) International Working Group response criteria ASAS20 (≥20% improvement in ≥3 of 4 domains: patient's global assessment [PGA], pain, function, and inflammation), ASAS 40 (≥40% improvement in 3 of 4 domains), ASAS 5/6 (≥20% improvement in 5 of 6 domains [the 4 ASAS domains, CRP, and spinal mobility]), partial remission (PR) criteria (<20 on a 0–100 scale in all 4 ASAS domains), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The primary endpoint was ASAS20 at Wk 12. Starting at Wk 12, pts were eligible for early-escape therapy (EET) with open-label (OL) adalimumab 40 mg eow. At Wk 24, all pts were switched to OL adalimumab 40 mg eow for up to 5 years. TSA was determined by investigators' evaluation of pre-enrollment spine x-rays. This abstract presents 2-year data of ATLAS pts with TSA according to duration of exposure to adalimumab.Results: Eleven out of 315 pts enrolled had TSA (5 PBO, 6 adalimumab). Baseline demographics and disease activity for PBO and adalimumab arms respectively were: HLA-B27 + (5, 4), male gender (5, 4), mean BASDAI (6.1, 7.6) and mean CRP (2.9, 3.3 mg/dL). Table 1 summarizes the efficacy variables at Wks 12 and 24 of the controlled period and after 1 and 2 years of total adalimumab exposure. (Table note: ADA=adalimumab; *Observed: Week 24 analyses exclude pts who went into EET (4 PBO, 2 ADA). **Observed, based on total duration of ADA exposure, blinded and open-label.) In comparison, efficacy results for the overall ATLAS population after 2 years of exposure are 79% for ASAS20, 67% for ASAS40, 49% for ASAS 5/6, 39% for ASAS PR, and 71% for BASDAI50. Among the TSA pts, only 1 achieved ASAS PR after 1 year of exposure and none at 2 years. This was because only 1 pt achieved a value <20 for function, whereas more pts had scores <20 in the other domains at both 1 and 2 years of adalimumab exposure. There were no serious adverse events (AEs) or deaths reported among the TSA patients. No AEs resulted in discontinuation of study drug. Study Wk 12 Study Wk 24 1 Yr Duration ADA n=11 2 Yr Duration ADA n=8 PBO n=5 ADA n=6 PBO n=1 ADA n=4 ASAS20 0 50 0 100 73 75 ASAS40 0 33 0 50 36 63 ASAS 5/6 0 33 0 75 55 38 ASAS partial remission 0 0 0 0 9 0 BASDAI50 0 33 0 75 45 63 Conclusion: In patients with TSA, adalimumab therapy provides rapid and significant improvement in signs and symptoms of active AS. This efficacy is maintained through 2 years. No significant safety issues were observed.Citation: Ann Rheum Dis, volume 66, supplement II, year 2007, page 412Session: Spondylarthropathies