OP0104 THE IMPACT OF PERSISTENT INFLAMMATORY CHANGES ON PREVALENCE OF FATTY LESIONS IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS TREATED WITH CERTOLIZUMAB PEGOL: 4-YEAR MRI RESULTS FROM RAPID-AXSPA

Background: Axial spondyloarthritis (axSpA) is a chronic disease characterised by inflammation in the sacroiliac joints and spine, causing severe back pain and stiffness. Emerging evidence suggests chronic spinal inflammation may be associated with osteoproliferation leading to syndesmophyte formation and spinal ankylosis, with subsequent worsening of patient mobility and function.1 Fatty lesions (FLs) on magnetic resonance imaging (MRI) T1 sequences are considered to be post-inflammatory precursors to these changes. Certolizumab pegol (CZP), an Fc-free, PEGylated tumour necrosis factor inhibitor (TNFi), has proven efficacy in treating the signs and symptoms of axSpA.2,3 CZP has also been shown to decrease spinal and sacroiliac joint MRI inflammation, and limit radiographic progression of the spine over 4 years of treatment.4 Objectives: To report the effect of early post-baseline (BL) inflammatory changes on fatty lesion prevalence over 4 years in a broad axSpA patient population treated with CZP. Methods: RAPID-axSpA (NCT01087762) was a phase 3 trial which was double-blind and placebo (PBO)-controlled to Week (Wk) 24, dose-blind to Wk 48 and open-label to Wk 204. CZP-randomised axSpA patients (Wk 0 CZP: 200 mg every 2 wks [Q2W] or 400 mg Q4W) continued their assigned dose throughout; PBO-randomised axSpA patients (Wk 0 PBO) received CZP from Wk 24, or if non-responders, from Wk 16 onwards. Blinded spinal MRI scans at Wks 0, 12, 48, 96 and 204 were assessed by 2 central readers to evaluate FL and inflammatory lesions in vertebral edges (VEs). Changes in FL prevalence are reported as odds ratios (OR; FL+/FL-) between time points or inflammation states, with nominal 95% confidence intervals (CI), for Wk 0 CZP. ORs were estimated from a logistic regression model for VE level data with random effects for patient and VE (within patient). The fixed model effects included time point, inflammatory status of VEs at BL and Wk 12, FL status at BL, and interactions if appropriate. Results: Of 325 axSpA patients, 89 and 47 initially randomised to CZP or PBO, respectively, had a BL and ≥1 post-BL MRI and therefore were eligible for these analyses. In these patients, a total of 3,127 of VEs were assessed at BL; inflammation was observed in 21.6% and FL in 29.3% of VEs, equating to mean counts of 5.0 and 6.7 per patient; 10.5% of VEs had both inflammation and FL at BL. At BL, FLs were relatively more often observed in inflamed VEs vs non-inflamed VEs: OR (95% CI) of 3.30 (1.94, 5.61). This difference increased over time, as the OR of FL at Wk 204 vs BL was 2.82 (1.70, 4.66) in VEs that were inflamed at BL compared with 1.08 (0.79, 1.48) in VEs that were not inflamed at BL (Figure 1A). Resolution of inflammation by Wk 12 appeared to lower the risk of FL prevalence over 4 years. When adjusted for BL VE status with respect to inflammation and FL, if inflammation prevailed at Wk 12, the OR of FL vs no FL was 1.80 (0.93, 3.49) at Wk 48, 2.54 (1.32, 4.91) at Wk 96 and 3.91 (1.87, 8.15) at Wk 204 (Figure 1B). Conclusion: This is the first report from a clinical interventional PBO-controlled study in a broad axSpA population showing that inflammation that prevailed after the start of TNFi treatment was associated with increased FL prevalence over 4 years. Reduction of inflammation by Wk 12 mitigated the risk of FL over the long-term, indicating the importance of early, effective and long-term treatment targeting inflammation. Similarly, a complete and persistent reduction of inflammation appears to be critical in these patients. References: [1]Maksymowych WP. Ann Rheum Dis 2013;72:23–8; 2. Van der Heijde D. Rheumatology (Oxford) 2017;56:1498–509; 3. Deodhar A. Arthritis Rheumatol 2019;71:1101–11; 4. Van der Heijde D. Ann Rheum Dis 2018;77:699–705. Acknowledgments: This study was funded by UCB Pharma. Editorial services were provided by Costello Medical. Disclosure of Interests: Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Sebastian Kruse: None declared, Simone Auteri Shareholder of: UCB Pharma, Employee of: UCB Pharma, Natasha de Peyrecave Employee of: UCB Pharma, Tommi Nurminen Employee of: UCB Pharma, Thomas Kumke Employee of: UCB Pharma, Bengt Hoepken Employee of: UCB Pharma, Juergen Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Eli Lilly and Company, Medac, MSD (Schering Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi- Aventis, and UCB Pharma, Consultant of: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma