Researchers Present on Immunogenicity of Biosimilar Anti-TNF Agents

The potential for the development of antidrug antibodies (ADAs) is a key concern among prescribers who use all biologics that target tumor necrosis factor (TNF). Two presentations at the American College of Rheumatology (ACR) Annual Meeting in Chicago, Illinois, which will be held from October 19-24, 2018, will address the immunogenicity of biosimilars in patients with rheumatoid arthritis (RA) and other inflammatory diseases.

Pooled Analysis of Biosimilar Studies Show Impact of ADAs

Researchers conducted a pooled analysis of phase 3, randomized, double-blind clinical studies that compared the efficacy and safety of 3 biosimilars—SB4 (referencing etanercept), SB2 (referencing infliximab), and SB5 (referencing adalimumab)—to assess the immunogenicity of the 3 drugs and the potential impact of ADAs.¹

Each of the phase 3 studies used a validated electrochemiluminescence assay to measure immunogenicity, and patients who had immunogenicity results in each study were pooled. In total, the analysis included 1710 patients.

Across treatment groups, efficacy was greater in those who did not have ADAs, and in all treatment, the rate of response as measured by the ACR criteria for a 20% improvement was reduced in the presence of ADAs (odds ratio [OR], 2.01; 95% CI, 1.60-2.53; P <.0001). The mean improvement in disease activity score in a count of 28 joints was significantly greater in patients without ADAs (estimated difference, 0.33; 95% CI, 0.19-0.48; P <.0001).

The presence of ADAs was also associated with increase injection-site reaction and infusion-related reactions (OR, 1.78; 95% CI: 1.05-3.02: = .033), especially with infliximab (OR, 2.67; 95% CI, 1.04-6.89; P = .041) versus etanercept (OR, 1.72; 95% CI, 0.38-7.77; P = .478) and adalimumab (OR ,1.14; 95% CI: 0.41-3.13; P = .804).

New NOR-SWITCH Data Show Similar Occurrence of ADAs in Originator and Biosimilar Infliximab

The NOR-SWITCH study, which has been described previously, was a 52-week study funded by the Norwegian government to assess a nonmedical switch from reference infliximab to CT-P13 in 6 indications: spondyloarthritis (SpA), RA, psoriatic arthritis (PsA), plaque psoriasis (PP), Crohn disease (CD), and ulcerative colitis (UC).

A new analysis reports on the immunogenicity of infliximab in patient treated with the reference product versus those switched to CT-P13.²

A total of 20 patients entered the study with ADAs; 9 of these patients were in the reference arm and 11 were in the biosimilar arm. An additional 36 patients—17 in the reference arm and 19 in the biosimilar arm—developed ADAs during the 52-week treatment period, and no consistent differences in ADAs were observed among diseases. No patients with plaque psoriasis developed ADAs during the study. Patients with ADAs in both arms were more likely to discontinue treatment than patients without ADAs.

All ADA-positive sera were cross-reactive with both reference and biosimilar infliximab across 5 different batches of each drug. ADAs in 60% to 79% of patients recognized 7 synthetic peptides, with no significant difference between treatment arms. Interestingly, 2 epitopes were recognized only in samples from patients with UC and CD, ad not in patients with rheumatic diseases.

The authors concluded that ADAs occurred to similar degrees in the 2 study arms, and that most patients had no consistent difference in epitope specificity. However, research into the 2 epitopes recognized by patients with UC and CD is ongoing.

References

1. Emery P, Weinblatt ME, Smolen JS, et al. Impact of immunogenicity on clinical efficacy and administration related reaction in TNF inhibitors: a pooled analysis from three biosimilar studies in patients with rheumatoid arthritis. Presented at the American College of Rheumatology 2018 meeting, October 19-24, 2018; Chicago, Illinois. Abstract 1532. https://acrabstracts.org/abstract/impact-of-immunogenicity-on-clinical-efficacy-and-administration-related-reaction-in-tnf-inhibitors-a-pooled-analysis-from-three-biosimilar-studies-in-patients-with-rheumatoid-arthritis/.

2. Goll GL, Bolstad N, Iria I, et al. Immunogenicity of originator and biosimilar infliximab: anti-drug antibody occurrence, cross-reactivity and epitope specificities across six diseases. Analysis from a Norwegian randomized switching trial. Presented at the American College of Rheumatology 2018 meeting, October 19-24, 2018; Chicago, Illinois. Abstract 700. https://acrabstracts.org/abstract/immunogenicity-of-originator-and-biosimilar-infliximab-anti-drug-antibody-occurence-cross-reactivity-and-epitope-specificities-across-six-diseases-analyses-from-a-norwegian-randomized-switching-tri/.