Background/Purpose : Ankylosing spondylitis (AS) patients (pts) were found to respond better to TNF inhibitors (TNFi) if treated early in the disease course.¹ The actual disease onset and hence disease duration is not always known. Previously, younger age was found to have the largest positive impact on clinical outcomes following 12 weeks (wks) of adalimumab (ADA) treatment.² The objective of this analysis was to examine the impact of time since diagnosis, age, and number of prior NSAIDs as surrogates for disease duration on clinical outcomes in AS pts from ATLAS trial treated with ADA for 52 wks.

Methods : ATLAS^3,4 was a phase 3 randomized double-blind placebo(PBO)-controlled trial evaluating the safety and efficacy of originator ADA in pts with active AS who failed NSAID therapy. In this post hoc analysis, pts who received at least one dose of ADA during the PBO-controlled period or open label extension and received prior NSAID(s) at baseline (BL) were categorized by BL: (1) time since diagnosis (<2 vs ≥2; <5 vs ≥5; <10 vs ≥10 years [y]), (2) age (<35, 35–45, and >45 y), and (3) number of prior NSAIDs (≤ 2 vs >2). The effect of time since diagnosis, age, and number of prior NSAIDs on AS outcome measures following 52 wks of ADA treatment was examined.

Results : At wk 52, 274 pts had received at least one dose of ADA and had at least one prior NSAID at BL. A majority of pts were ≥5 y since AS diagnosis (188 [68.6%]), ≤45 y of age (163 [59.5%]), HLA-B27+ (213 [77.7%]), and had ≤2 prior NSAIDs (158 [57.7%]). Pts with shorter time since diagnosis were generally younger (late thirties). Across all subcategories, >70% of pts were male. The BL disease activity measures were numerically similar across most categories. Following 52 wks of ADA treatment, the proportions of pts achieving ASAS20 and ASAS40 responses were numerically higher and mean decreases in BASDAI and BASFI scores from BL larger in subcategories with shorter time since diagnosis, younger age, and fewer prior NSAIDs (Table). There were significant differences in ASAS40, BASDAI, and BASFI scores between time since diagnosis (<2 vs ≥2 and <5 vs ≥5 y) and age (<35 vs >45 y) subcategories.

Conclusion : Following 52 wks of ADA treatment, shorter time since diagnosis and younger age were associated with greater clinical responses and improvements in disease activity and functionality. Although younger age (<35 vs >45 y) had significant positive impact on the clinical outcomes similar to wk 12 results, shorter time since diagnosis (<2 vs ≥2 and <5 vs ≥5 y) was also associated with better 52-wk clinical outcomes. These results suggest that early effective treatment intervention may improve long-term clinical outcomes in AS pts.

References:

1.            Rudwaleit, M. et al. Ann Rheum Dis, 2004; 63:665−70.

2.            Sieper, J. et al., Arthritis Rheumatol. 2016; 68 (suppl 10).

3.            Van der Heijde, D. et al., Ann Rheum Dis, 2007; 67:1218-21.

4.            Sieper, J. et al., Ann Rheum Dis, 2012; 71:700-6.