P193 Clinical features of patients with active ankylosing spondylitis who did not respond to adalimumab but responded to ixekizumab: a post-hoc analysis
Authors: Baraliakos Xenofon , Bolce Rebecca , Calderon David Sandoval , Leage Soyi Liu , Geneus Vladimir , Adams David , Deodhar Atul , Walsh Jessica , Sieper Joachim 
Published: April 2021

Background/Aims 

Biologic treatment in ankylosing spondylitis (AS) are currently limited to TNF and IL-17A inhibitors (IL-17Ai). It is unknown whether there are predictors of AS patients who only respond to 1 of these mechanisms of action or respond to switching from TNF-blocker to IL-17Ai. This post-hoc analysis evaluated whether patients who did not respond to TNF inhibitor adalimumab (ADA) but did subsequently respond to IL-17Ai ixekizumab (IXE) differed from those that responded to both ADA and subsequent IXE.

Methods 

The analysis included patients from the phase-3 COAST-V trial in bio-naive patients with active AS (BASDAI≥4 and back pain≥4 on VAS of 0-10). There were 341 patients randomized 1/1/1/1 to IXE80mg/2weeks (wks) (Q2W), IXE 80mg/4wks (Q4W), ADA 40mg Q2W (reference arm), and placebo (PBO) for the 16-week blinded-treatment period. Of these, 329 entered the dose double-blind extended treatment period (wks16 to 52). Those who received PBO or ADA were re-randomized to receive IXE 80mg Q4W or Q2W. Patients were stratified as responders or non-responders based on their Assessment of Spondyloarthritis International Society (ASAS) 40 response at wks16 and 52. Data for the 2 IXE dose groups were pooled.

Results 

Overall, more patients responded to IXE than ADA at wk16. Based on ASAS40 response at wks16 and at wk52, 30.9% of patients responded to both initial ADA and subsequent IXE, 23.5% of patients did not respond to initial ADA but did respond to subsequent IXE, 45.9% of patients responded to IXE at both time points, and 12.3% of patients did not respond to IXE at wk16 but did so at wk52. Across the groups, patients were of similar age and predominantly males, though there were proportionally more women among those who did not respond to either ADA or IXE at wk16. However, ADA non-responders at wk16/IXE responders at wk52 had numerically lower baseline (mean[SD]) C-reactive protein (11.2 [11.2]), lower MRI Spondyloarthritis Research Consortium of Canada (SPARCC) scores of the spine (11.6 [12.1]), and lower MRI SPARCC score of the sacroiliac joints (1.1 [2.2]) than ADA responders at wk16/IXE responders at wk52 patients (16.0 [17.1], 24.6 [32.6], and 5.5 [9.8]), respectively.

Conclusion 

In this analysis, patients who did not respond to ADA but subsequently responded to IXE exhibited overall lower levels of inflammation, as measured by CRP and MRI of the spine or sacroiliac joints, compared with patients who responded on ADA and also after switching to IXE. Along with comparative findings in patients who continuously received IXE and responded at both wks16 and 52 or wk52 only, these data indicate that IXE is efficacious in patients with active AS irrespective of inflammation level, assessed by CRP and MRI. Alternatively, lower baseline inflammation may be a predictor of delayed response.

Disclosure 

X. Baraliakos: Consultancies; X. Baraliakos has served as a consultant for AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB Pharma. Grants/research support; X. Baraliakos has received research grants from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB Pharma. R. Bolce: Shareholder/stock ownership; R. Bolce is a shareholder and employee of Eli Lilly and Company. D. Sandoval Calderon: Shareholder/stock ownership; D. Sandoval Calderon is a shareholder and employee of Eli Lilly and Company. S. Liu Leage: Shareholder/stock ownership; S.L. League is a shareholder and employee of Eli Lilly and Company. V. Geneus: Shareholder/stock ownership; V. Geneus is a shareholder and employee of Eli Lilly and Company. D. Adams: Shareholder/stock ownership; D. Adams is a shareholder and employee of Eli Lilly and Company. A. Deodhar: Consultancies; A. Deodhar has served as a consultant for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Galapagos NV, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB Pharma. Grants/research support; A. Deodhar has received grants from AbbVie, Eli Lilly and Company, GlaxoSmithKline, Novartis, Pfizer, and UCB Pharma. J. Walsh: Consultancies; J. A. Walsh has received consultancy fees from AbbVie, Eli Lilly and Company, Novartis, and UCB Pharma. Grants/research support; J. A. Walsh has received grant/research support from AbbVie and Pfizer. J. Sieper: Consultancies; J. Sieper is a consultant for: AbbVie, Eli Lilly and Company, Novartis, Merck, Janssen, Pfizer. Other; J. Sieper has served as a speaker for: AbbVie, Janssen, Novartis, Merck, Pfizer, and UCB.