Effectiveness and retention of certolizumab pegol and JAK inhibitors in rheumatoid arthritis: a multicenter retrospective study stratified by rheumatoid factor status.

Background: Patients with rheumatoid arthritis (RA) and high levels of Rheumatoid Factor (RF) often present with a higher inflammatory burden and may show a reduced response to JAK inhibitors (JAKi). However, previous studies have demonstrated that certolizumab pegol (CZP) provides comparable efficacy in patients regardless of RF level. Objectives: To compare the effectiveness and treatment retention of CZP versus JAKi in patients with RA according to baseline RF levels, assessing (a) changes in disease activity at 6 and 12 months, and (b) treatment retention over a 3-year follow-up period. Methods: This multicentre retrospective cohort included RA patients initiating CZP or JAKi (baricitinib, filgotinib, tofacitinib, upadacitinib) between 2010 and 2024. Patients were stratified by baseline RF levels (RF < 189 IU/mL and RF ≥ 189 IU/mL). Disease activity was assessed using DAS28-ESR at baseline, 6, and 12 months. Drug retention was analysed using Cox regression models, with a 3-year follow-up. A sensitivity analysis using IPTW was performed to account for baseline differences, while MICE and MNAR sensitivity analysis addressed missing data and informative missingness. Results: The study included 370 RA patients (409 treatment episodes: 234 CZP, 175 JAKi). Among patients with RF ≥ 189 IU/mL, CZP was associated with a greater reduction in DAS28-ESR than JAKi at both 6 and 12 months, with statistically significant differences at 12 months. In contrast, among patients with RF < 189 IU/mL, a greater reduction in DAS28-ESR at 6 months was observed in the JAK inhibitor group. CZP also demonstrated substantially higher drug retention at 3 years. In IPTW-weighted analyses, CZP was associated with a greater improvement in disease activity at 12 months in patients with RF ≥189 IU/mL, while treatment retention was numerically higher with CZP than with JAKi in this subgroup. However, the 12-month difference in clinical efficacy did not remain statistically significant under the MNAR sensitivity analysis. Conclusion: This study suggests that CZP may be associated with greater improvement in disease activity at 12 months in patients with RA and high RF levels, although this finding did not remain statistically significant under the MNAR sensitivity analysis and should therefore be interpreted with caution. A numerical difference in treatment retention favouring CZP was also observed. These findings highlight the potential importance of considering RF levels when selecting treatment and warrant further investigation in prospective studies.