Patients with rheumatoid arthritis and high rheumatoid factor demonstrate better clinical outcomes, and maintain drug concentration, when treated with certolizumab pegol vs. adalimumab, according to data published in Rheumatology.

"[Rheumatoid factor] is an autoantibody directed against the crystallizable fragment (Fc) region of IgG, and is characteristically found in patients with RA," Josef S. Smolen, MD, of the Medical University of Vienna, in Austria, and colleagues wrote.

"Despite all [TNF inhibitors (TNFis)] having the same mechanistic target, they bear different structural features," they added. "For example, [certolizumab pegol (CZP)] is a TNFi without an Fc fragment whereas other TNFis possess an Fc fragment. Of note, a decreased response to treatment with TNFis in patients with RA has been associated with RF positivity, particularly with high levels of RF. More recent preliminary data suggest that this decreased response may be associated with the presence of an Fc fragment."

To compare drug concentrations and efficacy between adalimumab (Humira, Abbvie), which contains an Fc fragment, and certolizumab pegol (Cimzia, UCB), with does not, in rheumatoid arthritis cohorts with either higher or lower rheumatoid factor (RF), Smolen and colleagues conducted a post-hoc analysis of data from the phase 4 EXXELERATE study. The analysis included 453 adults with active RA randomly assigned to take certolizumab pegol, with 454 randomly assigned to adalimumab, both in combination with methotrexate.

Study participants were classified by their level of RF, with those in the third quartile or lower -- 204 IU/mL or less -- separated from those above that level. The quartile cut-offs were "chosen to allow for a reasonable number of patients in each subgroup," the researchers wrote. Participants were followed for 104 weeks.

According to the researchers, the lower RF cohort demonstrated higher drug plasma concentrations of adalimumab than the higher RF cohort, but concentrations of certolizumab pegol were similar between the two groups.

As for efficacy, the lower RF group showed similar mean DAS 28-CRP at 104 weeks if they were treated with certolizumab pegol. However, in the higher RF group, those taking certolizumab pegol demonstrated lower mean DAS28-CRP (2.5; standard deviation = 1.2) than those taking adalimumab (2.9; SD = 1.2).

At week 104, 65.7% of higher RF participants treated with certolizumab pegol achieved DAS28-CRP low disease activity vs. 48.3% of those treated with adalimumab.

"Patients with RA and high levels of RF are a subgroup of patients with poor clinical outcomes," Smolen and colleagues wrote. "In [adalimumab (ADA)]-treated patients, clinical outcomes were poorer and drug concentration lower in patients with high RF levels compared with lower RF levels.

"However, in CZP-treated patients, those with high levels of RF had similar drug concentration and clinical outcomes to patients with lower levels of RF," they added. "Thus, the current data are the first from a head-to-head trial comparing CZP and ADA to show that response to therapy in patients with RA and high levels of RF is influenced by the presence or absence of an Fc-portion, which is in line with previous findings."