ADALIMUMAB TREATMENT MAINTAINS EFFICACY AND SAFETY IN PATIENTS WITH ANKYLOSING SPONDYLITIS (AS) — 2-YEAR RESULTS FROM ATLAS

Background: The Adalimumab Trial Evaluating Long-Term Efficacy and Safety in AS (ATLAS) was a randomized, placebo (PBO)-controlled, double-blind, Phase III study conducted in the US and Europe.Objectives: To assess the ability of adalimumab, an anti-TNF agent, to maintain both reduction of signs and symptoms and induction of partial remission over two years in ATLAS patients (pts).Methods: ATLAS enrolled pts with active AS who had an inadequate response to at least one 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 criteria 20 response at Week 12 (≥20% improvement in ≥3 of 4 domains: patient's global assessment [PGA], pain, function, and inflammation), the ASAS 40 [≥40% improvement in 3 of 4 domains] and ASAS 5/6 [≥20% improvement in 5 out of 6 domains [the 4 ASAS domains, CRP, and spinal mobility]). The primary endpoint was ASAS20 at Wk 12. Starting at Wk 12, pts were eligible for early-escape therapy (EET) of open-label adalimumab 40 mg eow. At Wk 24, all pts were switched to open-label (OL) adalimumab 40 mg eow for an additional 80 wks. This abstract presents 2-year (yr) data of ATLAS patients according to duration of exposure to adalimumab.Results: During the first 12 and 24 wks of DB exposure, adalimumab pts showed a statistically significant reduction in signs and symptoms (ASAS20) compared to placebo and some achieved partial remission. After conversion to OL adalimumab, this improvement was sustained through 104 wks of adalimumab treatment (see table). Adalimumab has a safety profile similar to that seen in rheumatoid arthritis and psoriatic arthritis trials. The following adverse events (AE) rates were observed per 100 pt yrs in the DB vs. 2 yrs of adalimumab exposure, respectively: Serious AEs: 10.2/10.5; serious infectious AEs: 0, 1.1; AEs leading to discontinuation: 3.8/4.5; malignant AEs: 0.0, 0.9. At 2 yrs of exposure, AEs ≥ 5% included nasopharyngitis, upper respiratory tract infection, and headache. There were no cases of tuberculosis, lupus-like symptoms, demyelinating disease, or death. ASAS Response to Adalimumab Exposure to 2 Years Response at Study Response at Study 52 Wks of Exposure 104 Wks of Exposure Point Week 12 Point Week 24 to Adalimumab n/N (%) to Adalimumab n/N (%) N (%)* N (%)* n/TOTAL (%)†‡ n/TOTAL (%)†‡ ASAS20 Placebo (N=107) 22 (21) 19 (18) | | Adalimumab (N=208) 121 (58) 105 (51) 196/276 (71) 137/173 (79) ASAS40 Placebo (N=107) 15 (14) 15 (14) | | Adalimumab (N=208) 85 (41) 82 (39) 141/276 (51) 115/173 (67) ASAS 5/6 Placebo (N=107) 14 (13) 12 (11) | | Adalimumab (N=208) 101 (49) 93 (45) 165/276 (60) 89/180 (49) Partial Remission Placebo (N=107) 4 (4) 43 (21) | | Adalimumab (N=208) 6 (6) 46 (22) 94/276 (34) 68/174 (39) *Imputed; †Obsrvd; ‡Not all had 2 yrs ADA @ analysis time. |All pts on ADA after Wk 24. Conclusion: Adalimumab was efficacious in reducing signs and symptoms and inducing partial remission in AS patients. This effect was maintained through 2 years of exposure. No new safety issues were observed over 2 years of exposure.Citation: Ann Rheum Dis, volume 66, supplement II, year 2007, page 411Session: Spondylarthropathies