Investigators Present Data on ADA Development, TDM for Biosimilar Adalimumab

The advent of biosimilar adalimumab in the European Union was among the most eagerly awaited events for biosimilar stakeholders in 2018. During this week’s European Crohn’s and Colitis Organisation’s 14th Congress, held in Copenhagen, Denmark, research teams are presenting findings concerning one of those adalimumab biosimilars: Amgen’s ABP 501, sold in the European Union as Amgevita.

First, researchers from Amgen and from the Medical University of Vienna in Vienna, Austria, will present a post hoc analysis that seeks to identify factors that influence the development of binding anti-drug antibodies (ADAs) to adalimumab.¹

The researchers analyzed data from the randomized, double-blind, 26-week, active-controlled study that was used to support a demonstration of clinical equivalence between the biosimilar and the reference adalimumab in adalimumab-naïve patients with rheumatoid arthritis (RA).

Validated assays were used to detect the presence of binding ADAs, and the investigators used a logistic regression to the week 26 ADA status in patients who were ADA-negative at week 12.

Of 526 patients tested, 353 patients tested negative for binding ADAs thorough week 12, and 52 patients developed binding ADAs at week 26.

They found that baseline factors, including body mass index, albumin, glucose, platelet count, and C-reactive protein did not correlate with development of binding ADAs; however, log-transformation of pharmacokinetic (PK) trough at week 12 was strongly correlated with the development of binding ADAs at week 26.

“Earlier monitoring of PK levels may provide insight into ADA formation in patients treated with adalimumab,” they concluded.

Second, researchers from Spain will report on a therapeutic drug monitoring (TDM) test that has been validated for use with the biosimilar agent.²

The Promonitor-ADL test is frequently used to monitor patients with inflammatory bowel disease who are treated with adalimumab, and the research team will report that they validated this test for the quantification of the biosimilar in comparison with its reference.

The researchers used requirements set forth under the Clinical and Laboratory Standards Institute’s guideline for the lower limit of quantification (LLOQ) and for imprecision and bias. LLOQ was determined with 4 human serum sample matrices per each of 3 low-level adalimumab concentrations, replicated 3 times per 2 lots of the testing kit for the reference and biosimilar over 3 days. Imprecision was evaluated using 3 replicates of 5 sample matrices that represented clinically relevant adalimumab concentrations.

The investigators found that the test can equally measure adalimumab either in the reference biologic or in the biosimilar product; the test was able to quantify ABP 501 in the measurement range of 0.9 to 10.9 mcg/mL with a bias estimate of −0.089 to 0.306 mcg/mL, and with an overall imprecision of 6% to 9%.

The test “can equivalently measure either the reference ADL or the approved biosimilar AMGEVITA with the same sensitivity, precision and accuracy,” write the authors.

References

1. Reinisch W, Rauter I, Chen L, Gessner M, Fanjiang G. Factors that may influence the development of anti-drug antibodies to adalimumab. Presented at: 14th Congress of the European Crohn’s and Colitis Organisation; March 6-9, 2019; Copenhagen, Denmark. Abstract P624. ecco-ibd.eu/publications/congress-abstract-s/item/p624-factors-that-may-influence-the-development-of-anti-drug-antibodies-to-adalimumab.html/.

2. Ruiz-Argüello MB, Maguregui A, Martínez A, Nagore D. Adalimumab therapeutic drug monitoring test validated for measuring ABP 501 biosimilar. Presented at: 14th Congress of the European Crohn’s and Colitis Organisation; March 6-9, 2019; Copenhagen, Denmark. Abstract P329. ecco-ibd.eu/publications/congress-abstract-s/item/p329-adalimumab-therapeutic-drug-monitoring-test-validated-for-measuring-abp-501-biosimilar.html.