POS0918 EVALUATION OF SPINAL RADIOGRAPHIC PROGRESSION IN PATIENTS WITH RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS RECEIVING IXEKIZUMAB THERAPY OVER 2 YEARS
Authors: Van der Heijde D. , Østergaard M. , Reveille J. D. , Baraliakos X. , Kronbergs A. , Sandoval D. , Li X. , Carlier H. , Adams D. , Maksymowych W. P. 
Published: May 2021

Background:

It is important to understand the potential effect long-term therapy with biologics can have on structural changes in the spine among patients with active radiographic axial spondyloarthritis (r-axSpA, ankylosing spondylitis).

Objectives:

We examined radiographic progression in the spine among patients with active r-axSpA treated with ixekizumab, an IL-17A antagonist, for 2 years, and potential predictors of spinal radiographic progression.

Methods:

Patients with active r-axSpA, biologic-naive (COAST-V, NCT02696785) or with prior experience with a maximum of 2 TNF inhibitors (COAST-W, NCT02696798), received 80 mg ixekizumab every 2 or 4 weeks for 2 years (108 weeks, of which 56 weeks were the COAST-Y extension study, NCT03129100). Mean change from baseline of modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) (average score from 2 selected readers, blinded for time order) for patients treated with ixekizumab for 2 years with data at both baseline and year 2 is presented (N=230; 54% of total randomized patients). Non-progression is presented for all patients and subgroups based on TNFi-experience. Predictors were identified in multivariate logistic regression models with stepwise selection criteria of p-value <0.1. All data are observed.

Results:

At baseline, patients (N=230) were predominately male (82%) with an average age of 43 years, mean symptom duration of 16 years, 52% were TNFi-experienced, mean (SD) ASDAS score was 4.0 (0.7), most were HLA-B27 positive (87%) and 40% had syndesmophytes (identified by both selected readers at the same location). Baseline mSASSS (SD) was 11.0 (16.3) and change from baseline at year 2 of treatment was 0.3 (1.8) (Table 1). The proportion of non-progressors (mSASSS change from baseline <2) over 2 years was 89.6% (total IXE [all patients]), 90.9% (biologic-naive) and 88.3% (TNFi-experienced), and, if defined as mSASSS change from baseline ≤0, 75.7% (total IXE [all patients]), 78.2% (biologic-naive) and 73.3% (TNFi-experienced) (Table 1). Predictors of structural progression at year 2 (mSASSS change >0) were age, baseline syndesmophytes, HLA-B27 status and gender (Table 1). Week 52 inflammation in MRI SPARCC spine was also identified as a predictor for structural progression at year 2 in a separate model for patients from COAST-V where MRI measures were available at baseline and Week 52 (N=109).

Conclusion:

The majority of patients treated with ixekizumab for 2 years did not show radiographic progression, and the overall mean progression was low. Similar levels of non-progression were observed in biologic-naive patients and patients previously exposed to TNFis. Predictors were generally consistent with previous studies.

Table 1.

Spinal radiographic changes for patients with active r-axSpA treated with ixekizumab for 2 years

Change in mSASSS at year 2All patientsa
N=230Biologic-naive
N=110TNFi-experienced
N=120 Baseline mSASSS, mean (SD)11.0 (16.3)10.1 (15.5)11.7 (17.0) Change at year 2, mean (SD)0.3 (1.8)0.3 (2.0)0.4 (1.6) Change in total mSASSS <2, n (%)206 (89.6)100 (90.9)106 (88.3) Change in total mSASSS ≤0, n (%)174 (75.7)86 (78.2)88 (73.3)Multivariable logistic regression model
Prediction for change in total mSASSS >0, OR (95% CI), p-valueAll patientsa,bN=228 Age (≥40 years vs. <40 years)2.97 (1.41, 6.28)p=0.004c Baseline syndesmophytesb (yes vs. no)2.31 (1.18, 4.54)p=0.015c Baseline HLA-B27 (positive vs. negative)3.78 (1.04, 13.75)p=0.044c Gender (male vs. female)3.16 (1.01, 9.86)p=0.047c Baseline ASDAS state (>3.5 vs. [2.1, 3.5])2.26 (0.96, 5.34)p=0.063

aCombined ixekizumab group of Q2W and Q4W patients with baseline and year-2 mSASSS data

bIdentified by both selected readers at the same location (2 patients were not evaluable by both readers)

cp<0.05

Abbreviations: ASDAS=Assessment of Disease Activity, CI=confidence interval, IXE=ixekizumab, mSASSS=modified Stoke Ankylosing Spondylitis Spinal Score, OR=odds ratio, Q2W=every 2 weeks, Q4W=every 4 weeks, SD=standard deviation, TNFi=tumor necrosis factor inhibitor

Disclosure of Interests:

Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma, Employee of: Director of Imaging Rheumatology bv., Mikkel Østergaard Consultant of: AbbVie, BMS, Boehringer-Ingelheim, Eli Lilly and Company, Janssen, Merck, Pfizer, Roche, UCB, Celgene, Sanofi, Regeneron, Novartis, Grant/research support from: AbbVie, BMS, Merck, UCB, Celgene, Novartis, John D Reveille Paid instructor for: UCB, Eli Lilly and Company, Consultant of: UCB, Eli Lilly and Company, Pfizer, Novartis, Grant/research support from: Janssen, Eli Lilly and Company, Xenofon Baraliakos Speakers bureau: Abbvie, BMS, Lilly, Janssen, Novartis, MSD, Pfizer, Galapagos, Gilead, UCB, Paid instructor for: Abbvie, BMS, Lilly, Janssen, Novartis, MSD, Pfizer, Galapagos, Gilead, UCB, Consultant of: Abbvie, BMS, Lilly, Janssen, Novartis, MSD, Pfizer, Galapagos, Gilead, UCB, Andris Kronbergs Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, David Sandoval Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Xiaoqi Li Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Hilde Carlier Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, David Adams Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Walter P Maksymowych Speakers bureau: Abbvie, Janssen, Novartis, Pfizer, UCB, Consultant of: Abbvie, Boehringer, BMS, Eli Lilly and Company, Novartis, Pfizer, UCB, Grant/research support from: Abbvie, Novartis, Pfizer