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P624 Factors that may influence the development of anti-drug antibodies to adalimumab

W. Reinisch*1, I. Rauter2, L. Chen3, M. Gessner3, G. Fanjiang3

1Medical University of Vienna, Vienna, Austria, 2Amgen (Europe) GmbH, Rotkreuz, Switzerland, 3Amgen Inc., Thousand Oaks, USA

Background

Anti-drug antibodies (ADAs) to adalimumab (both the originator and biosimilars) are associated with a loss in efficacy and infusion reaction. ABP 501 [EU: AMGEVITA® (adalimumab); US: AMJEVITA™ (adalimumab-atto)] is the first approved biosimilar to adalimumab. Earlier identification of ADAs would help optimise treatment with adalimumab. In this post-hoc analysis, we aim to identify factors that may influence the development of binding ADAs to adalimumab.

Methods

We analysed data from a randomised, double-blind, 26-week, active-controlled study designed to show clinical equivalence between ABP 501 40 mg and adalimumab reference product 40 mg among adalimumab-naive adult patients with moderate-to-severe rheumatoid arthritis. Validated electrochemiluminescent assays were used to detect the presence of binding ADAs to adalimumab. We fitted a logistic regression to the Week 26 ADA binding status (positive or negative) in subjects who had negative ADA at Week 12. Factors that were explored included baseline BMI (underweight, normal, overweight, or obese), albumin, glucose, platelet counts, C-reactive protein (CRP), change in CRP from baseline to Week 12, and serum pharmacokinetic (PK) trough at Week 12. A stepwise selection procedure with entry criterion of 0.3 and stay criterion of 0.2 was used in a multi-variable logistic regression. Variables with p < 0.05 were considered to strongly correlate with the development of binding ADA at Week 26.

Results

Of 526 subjects tested, 353 showed negative for binding ADAs to adalimumab through Week 12, with 52 subjects developing binding ADA to adalimumab at Week 26. Average baseline BMI was 28 with 31% obese. Mean (SD) was 42 (2.8) g/l for albumin; 5.6 (1.7) mmol/l for glucose; 290.6 (84.55) 109/l for platelet count; 14.4 (21.45) mg/l for CRP; −7 (19.7) mg/l for change of CRP from baseline at Week 12; 7152 (2723) ng/ml for trough PK at Week 12 for ADA negative patients; 5755 (2810) ng/ml for trough PK at Week 12 for ADA-positive patients. The final multi-variable logistic regression showed that log-transformation of PK trough at Week 12 strongly correlated with the development of binding ADA at Week 26. The odds ratio (95% CI) for log-transformation of PK trough at Week 12 was 0.31 (0.17, 0.56), p < 0.01.

Conclusion

Baseline factors, such as BMI, albumin, glucose, platelet count, and CRP, did not correlate with the development of binding ADAs to adalimumab. A lower PK trough in ADA-negative patients may be strongly correlated to developing binding ADAs later in their course of adalimumab therapy. While further studies are needed, earlier monitoring of PK levels may provide insight into ADA formation in patients treated with adalimumab.