The impact of persistent inflammatory changes on prevalence of fat lesions in patients with axial spondyloarthritis treated with certolizumab pegol: 4-year MRI results from rapid axSpA

Full text: Certolizumab pegol (CZP), an Fc-free, PEGylated tumor necrosis factor inhibitor has been shown to decrease spinal and sacroiliac joint MRI inflammation, and limit spinal radiographic progression over 4 years' treatment. Here, we report the effect of early post-baseline (BL) inflammatory changes on fat lesion (FL) prevalence over 4 years in CZP-treated axial spondyloarthritis (axSpA) patients. RAPID-axSpA was phase 3, double-blind and placebo (PBO)-controlled to Week (Wk) 24, dose-blind to Wk48 and open-label to Wk204. CZP-randomized patients (Wk0 CZP: 200mg every 2 weeks [Q2W] or 400mg Q4W) continued their assigned dose throughout; PBO-randomized patients received CZP from Wk24, or Wk16 if non-responders. Blinded spinal MRI scans were evaluated for FLs and inflammatory lesions in vertebral edges (VEs) at Wk0/12/48/96/204. FL prevalence changes are reported as odds ratios (estimated from a logistic regression model [OR; FL+/FL-]) between time points/inflammation states, with nominal 95% confidence intervals (CI), for Wk0 CZP. 89/325 CZP-randomized, and 47/325 PBO-randomized patients were eligible (BL+ ≥1 post-BL MRI). 2,047 VEs were assessed at BL: inflammation was observed in 21.2% (mean count: 5.0/patient), FL in 29.8% of VEs (mean count: 6.8/patient), and both in 10.6% of VEs. At BL, FLs were more often observed in inflamed vs non-inflamed VEs (OR:3.06; 95% CI:2.14,4.35). This difference increased over time (Figure 1A). Resolution of inflammation by Wk12 appeared to lower the risk of FL prevalence over 4 years (Figure 1B). This is the first report from a clinical interventional PBO-controlled study in a broad axSpA population showing that inflammation that prevailed after CZP initiation was associated with increased FL prevalence over 4 years. Reduction of inflammation by Wk12 reduced the risk of FL long-term, indicating the importance of early inflammation treatment in axSpA patients