Impact of high rheumatoid factor levels on treatment outcomes with certolizumab pegol and adalimumab in patients with rheumatoid arthritis

Objective: To assess the impact of baseline rheumatoid factor (RF) level on drug concentrations and efficacy of certolizumab pegol (CZP; tumour necrosis factor inhibitor [TNFi] without a crystallisable fragment [Fc]) and adalimumab (ADA; Fc-containing TNFi) in patients with rheumatoid arthritis (RA). Methods: The phase 4 EXXELERATE study (NCT01500278) was a 104-week, randomised, single-blind (double-blind until Week 12; investigator-blind thereafter), head-to-head study of CZP versus ADA in patients with RA. In this post hoc analysis, we report drug concentration and efficacy outcomes stratified by baseline RF quartile (≤Q3 or >Q3). Results: Baseline data by RF quartiles were available for 453 CZP-randomised and 454 ADA-randomised patients (≤Q3: ≤204 IU/mL; >Q3: >204 IU/mL). From Week 12, the area under the curve (AUC) of ADA concentration was lower in patients with RF >204 IU/mL versus patients with RF ≤204 IU/mL; the AUC of CZP concentration was similar in patients with RF ≤204 IU/mL and >204 IU/mL. For patients with RF ≤204 IU/mL, disease activity score (DAS28)-C-reactive protein (CRP) was similar between CZP- and ADA-treated patients through Week 104. For patients with RF >204 IU/mL, mean DAS28-CRP was lower in CZPversus ADA-treated patients at Week 104. The proportion of patients with RF >204 IU/mL achieving DAS28-CRP low disease activity at Week 104 was greater in CZP- versus ADA-treated patients. Conclusion: CZP was associated with maintained drug concentration and efficacy in patients with RA and high RF and may therefore be a more suitable therapeutic option than TNFis with an Fc fragment in these patients.