THU0201 Factors Associated with Structural Damage in the Spine, as Measured by X-ray, in Patients with Axial Spondyloarthritis Treated with Certolizumab Pegol Over 96 Weeks
Authors: D. van der Heijde, W.P. Maksymowych, R. Landewé, C. Stach, B. Hoepken, O. Davies, T. Nurminen, J. Braun
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> There are several risk factors known to be associated with radiographic damage and progression in the spine in patients (pts) with axial spondyloarthritis (axSpA). <h3>Objectives</h3> To investigate baseline (BL) characteristics of axSpA associated with increased BL structural damage on X-rays of the spine and to identify subgroups with increased risk of structural progression to Week (Wk) 96 of RAPID-axSpA. <h3>Methods</h3> RAPID-axSpA (NCT01087762)<sup>1</sup> is an ongoing phase 3 trial (PBO-controlled to Wk24) investigating certolizumab pegol (CZP) treatment in pts with axSpA, stratified by fulfillment of mNY criteria: ankylosing spondylitis (AS) and non-radiographic (nr-)axSpA. X-rays were recorded in a subset of pts (imaging set) and scored by mSASSS at BL and Wk96 by 2 readers (average scores used). Observed values are reported for all pts with available X-rays at BL (BL analyses), or BL and Wk96 (mSASSS progression analyses). Multiple regression analyses were adjusted for BL disease duration and age, and models fitted including all analyzed BL characteristics. No adjustments were made for treatment effect (ie. BL randomization: CZP or PBO) as no differences were observed in mSASSS progression between groups. <h3>Results</h3> 325 pts were randomized, of whom 163 were in the imaging set; 161 had BL X-rays, and 134 both BL and Wk96 X-rays. Mean (SD) BL mSASSS was 7.8 (14.5) (AS: 11.2 [16.6]; nr-axSpA: 3.2 [9.6]). Age, disease duration, BMI ≥30 and male gender were independently associated with BL mSASSS (Table A). Structural progression to Wk96 was limited (mSASSS mean change [SD]: 0.4 [1.5]; AS: 0.6 [1.7]; nr-axSpA: 0.2 [0.8]), occurring in few pts (7.5% had mSASSS progression ≥2; AS: 10.8%; nr-axSpA: 2.0%). Progression predominantly occurred in pts with BL damage: higher BL mSASSS associated with 0.03/mSASSS point increase, and presence of syndesmophytes at BL with 1.30 mSASSS worsening (p&lt;0.001). In males, increased progression occurred in current smokers, with 0.82 worsening of mSASSS. Furthermore, BL spinal inflammation (ASspiMRI-a &gt;2) was associated with 0.63 worsening of mSASSS to Wk96 (p=0.012). Evaluating further, mean ASspiMRI-a over time was considered: 1-point increase in SQRT (ASspiMRI-a) was associated with 0.43 worsening of mSASSS (p=0.004), although results were attenuated when adjusted for BL damage (mSASSS [p=0.030] or syndesmophytes [p=0.091]). When considering all analyzed factors using multiple regression, no BL factors were significantly and independently associated with progression (Table B). This lack of association may reflect the limited progression seen in this cohort over 96 wks; further assessment after a longer follow-up period is required. <h3>Conclusions</h3> BL data from RAPID-axSpA demonstrate that age, longer disease duration, male gender and higher BMI were associated with more severe structural damage at BL. Limited progression was observed to Wk96, and BL structural damage was found to be significantly associated with further structural progression. Spinal inflammation, at BL and over time, was associated with mSASSS progression, however, these findings were not independent of other variables. <h3>References</h3> Landewé R. Ann Rheum Dis 2014;73;39–47 <h3>Disclosure of Interest</h3> D. van der Heijde Grant/research support from: AbbVie, Amgen, AstraZeneca, Augurex, BMS, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB Pharma, Consultant for: AbbVie, Amgen, AstraZeneca, Augurex, BMS, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB Pharma, Employee of: Vertex Director of Imaging Rheumatology bv., W. Maksymowych Grant/research support from: Abbott, Amgen, Bristol Myers Squibb, Eli-Lilly, Janssen, Merck, Pfizer, Synarc and UCB Pharma, Consultant for: Abbott, Amgen, Bristol Myers Squibb, Eli-Lilly, Janssen, Merck, Pfizer, Synarc and UCB Pharma, Speakers bureau: Abbott, Amgen, Bristol Myers Squibb, Eli-Lilly, Janssen, Merck, Pfizer, Synarc and UCB Pharma, R. Landewé Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth, Consultant for: Abbott, Ablynx, Amgen, Astra-Zeneca, Bristol Myers Squibb, Centocor, Glaxo-Smith-Kline, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth, Speakers bureau: Abbott, Amgen, Bristol Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma, Wyeth., C. Stach Shareholder of: UCB Pharma, Employee of: UCB Pharma, B. Hoepken Employee of: UCB Pharma, O. Davies Shareholder of: UCB Pharma, Employee of: UCB Pharma, T. Nurminen Employee of: UCB Pharma, J. Braun Grant/research support from: Abbott, Bristol Myers Squibb, Celgene, Celltrion, Chugai, Johnson &amp; Johnson, MSD, Novartis, Pfizer, Roche, UCB Pharma, Consultant for: Abbott, Bristol Myers Squibb, Celgene, Celltrion, Chugai, Johnson &amp; Johnson, MSD, Novartis, Pfizer, Roche, UCB Pharma