Rheumatoid factor or interleukin-6 receptor inhibition predicts the long-term effectiveness of certolizumab pegol in Japanese patients with rheumatoid arthritis: A two-center retrospective study

Objectives To assess long-term retention rates associated with effectiveness of certolizumab pegol (CZP) and identify determinants of its effectiveness in patients with rheumatoid arthritis (RA). Methods This retrospective observational study enrolled 107 patients with RA. Retention rates based on effectiveness were investigated using the Kaplan–Meier method. Cox regression analysis was used to identify predictors of CZP effectiveness. In subgroup analyses, patients were categorized according to history of biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) to detect the determinants of CZP effectiveness in each group. Receiver operating characteristic analysis was performed to detect the optimal cut-off point for rheumatoid factor (RF). Results During a median of 56.0 months, overall retention rates at 12, 24, 48, and 60 months were 65.0%, 55.8%, 46.4%, and 40.2%, respectively. Multivariate analysis revealed that a b/tsDMARD-naïve group exhibited lowest likelihood of non-response to CZP (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.19–0.73, P  = 0.003). In the sub-analyses, RF titer (HR per 100 IU/mL increment: 1.25, 95% CI: 1.06–1.60, P  = 0.009) and prior interleukin-6 receptor (IL-6R) blockade (HR: 2.46, 95% CI: 1.11–5.57, P  = 0.027) were strong determinants for CZP ineffectiveness in the b/tsDMARD-naïve and b/tsDMARD-switched groups, respectively. Highest retention rate was observed in the b/tsDMARD-naive population with an RF of < 79.9 IU/mL. Conclusions Overall, b/tsDMRAD-naïve status was the strongest predictor of long-term CZP effectiveness. RF elevation in b/tsDMARD-naïve and preceding IL-6R inhibition in b/tsDMARD-switched populations are significantly associated with reduced therapeutic effects of CZP.