As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to certolizumab pegol in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

Patients with Crohn's disease were tested at multiple time points for antibodies to certolizumab pegol during Studies CD1 and CD2. In patients continuously exposed to CIMZIA, the overall percentage of patients who were antibody positive to CIMZIA on at least one occasion was 8%; approximately 6% were neutralizing in vitro. No apparent correlation of antibody development to adverse events or efficacy was observed. Patients treated with concomitant immunosuppressants had a lower rate of antibody development than patients not taking immunosuppressants at baseline (3% and 11%, respectively). The following adverse events were reported in Crohn's disease patients who were antibody-positive (N = 100) at an incidence at least 3% higher compared to antibody-negative patients (N = 1,242): abdominal pain, arthralgia, edema peripheral, erythema nodosum, injection site erythema, injection site pain, pain in extremity, and upper respiratory tract infection. 

In two long-term (up to 7 years of exposure), open-label Crohn's disease studies, overall 23% (207/903) of patients developed antibodies against certolizumab pegol on at least one occasion. Of the 207 patients who were antibody positive, 152 (73%) had a persistent reduction of drug plasma concentration, which represents 17% (152/903) of the study population. The data from these two studies do not suggest an association between the development of antibodies and adverse events.

The overall percentage of patients with antibodies to certolizumab pegol detectable on at least one occasion was 7% (105 of 1,509) in the rheumatoid arthritis placebo-controlled trials. Approximately one third (3%, 39 of 1,509) of these patients had antibodies with neutralizing activity in vitro. Patients treated with concomitant immunosuppressants (MTX) had a lower rate of antibody development than patients not taking immunosuppressants at baseline. Patients treated with concomitant immunosuppressant therapy (MTX) in RA-I, RA-II, RA-III had a lower rate of neutralizing antibody formation overall than patients treated with CIMZIA monotherapy in RA-IV (2% vs. 8%). Both the loading dose of 400 mg every other week at Weeks 0, 2 and 4 and concomitant use of MTX were associated with reduced immunogenicity. 

Antibody formation was associated with lowered drug plasma concentration and reduced efficacy. In patients receiving the recommended CIMZIA dosage of 200 mg every other week with concomitant MTX, the ACR20 response was lower among antibody positive patients than among antibody-negative patients (Study RA-I, 48% versus 60%; Study RA-II 35% versus 59%, respectively). In Study RA-III, too few patients developed antibodies to allow for meaningful analysis of ACR20 response by antibody status. In Study RA-IV (monotherapy), the ACR20 response was 33% versus 56%, antibody-positive versus antibody-negative status, respectively [see Clinical Pharmacology (12.3)]. No association was seen between antibody development and the development of adverse events. 

Approximately 8 % (22/265) and 19% (54/281) of subjects with psoriasis who received CIMZIA 400 mg every 2 weeks and CIMZIA 200 mg every 2 weeks for 48 weeks, respectively, developed antibodies to certolizumab pegol. Of the subjects who developed antibodies to certolizumab pegol, 45% (27/60) had antibodies that were classified as neutralizing. Antibody formation was associated with lowered drug plasma concentration and reduced efficacy.

A more sensitive and drug tolerant electrochemiluminesence (ECL)-based bridging assay was used for the first time in the nr-axSpA-1 study, resulting in a greater proportion of samples having measurable antibodies to certolizumab pegol and thus a greater incidence of patients being classed as antibody positive. In the placebo-controlled trial in patients with non-radiographic axial spondyloarthritis, after up to 52 weeks of treatment, the overall incidence of patients who were antibody positive to certolizumab pegol was 97% (248/255 patients). Of these antibody positive patients, higher titers were associated with reduced certolizumab pegol plasma levels.

The data above reflect the percentage of patients whose test results were considered positive for antibodies to certolizumab pegol in an ELISA or ECL-based bridging assay, and are highly dependent on the sensitivity and specificity of the assay.