{"doi":"10.1016/j.cgh.2021.01.006","title":"Patients With Low Drug Levels or Antibodies to a Prior Anti–Tumor Necrosis Factor Are More Likely to Develop Antibodies to a Subsequent Anti–Tumor Necrosis Factor","abstract":"Therapeutic drug monitoring (TDM) with measurement of serum drug and antidrug antibodies (ADAb) is used widely to confirm therapeutic exposure, rule out immunogenicity, and optimize treatment of biologics in patients with inflammatory bowel diseases.1Feuerstein J.D. Nguyen G.C. Kupfer S.S. et al.American Gastroenterological Association Institute guideline on therapeutic drug monitoring in inflammatory bowel disease.Gastroenterology. 2017; 153: 827-834Abstract Full Text Full Text PDF PubMed Scopus (319) Google Scholar A recent genome-wide association study found the variant HLA-DQA1∗05 to increase the risk of development of antibodies against infliximab (IFX) and adalimumab (ADM) 2-fold, regardless of concomitant immunomodulator use.2Sazonovs A. Kennedy N.A. Moutsianas L. et al.HLA-DQA1∗05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's disease.Gastroenterology. 2020; 158: 189-199Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar,3Wilson A. Peel C. Wang Q. et al.HLADQA1∗05 genotype predicts anti-drug antibody formation and loss of response during infliximab therapy for inflammatory bowel disease.Aliment Pharmacol Ther. 2020; 51: 356-363Crossref PubMed Scopus (26) Google Scholar However, there is currently limited evidence showing whether patients who develop antibodies to 1 anti–tumor necrosis factor (TNF) are prone to develop antibodies to the subsequent anti-TNF. Our aim was to investigate the risk of subsequent antibody development in cases (with ADAb to prior anti-TNF) versus control subjects (without ADAb to prior anti-TNF) using a large cohort of patients with inflammatory bowel diseases who underwent TDM with a drug-tolerant assay. Methods are described in the Supplementary Methods. Our study included 5828 subjects of whom 3616/5828 (62.0%) were first treated with IFX and then ADM and 2212/5828 (38.0%) were first treated with ADM and then IFX (Supplementary Table 1). Survival analysis showed that in patients who switched from IFX to ADM, ADAb to IFX was significantly associated with subsequent ADAb formation to ADM (P < .0001) (Figure 1A), with 28.5% of cases who developed ADAb to ADM versus 12.4% of control subjects (hazard ratio, 2.82; 95% confidence interval, 2.35–3.38; P < .0001) (Figure 1B). Increasing concentrations of ADAb to IFX were associated with higher proportions of patients developing ADAb to ADM (P < .0001). ADAb concentrations ≥10 U/mL were associated with a higher proportion of patients developing ADAb to ADM after switch versus those who had ADAb to IFX concentrations <10 U/mL (31.2% vs 21.5%, respectively; P < .0001). In patients who switched from ADM to IFX, survival analysis showed that ADAb to ADM was significantly associated with subsequent ADAb formation to IFX (P < .0001) (Figure 1C), with 39.1% of cases who developed ADAb to IFX versus 15.8% of control subjects (hazard ratio, 3.43; 95% confidence interval, 2.81–4.20; P < .0001) (Figure 1D). In contrast to patients switching from IFX to ADM, increasing concentrations of ADAb to ADM did not result in a significantly higher proportion of patients developing ADAb to IFX. Before switch from IFX to ADM, median (interquartile range) IFX serum concentrations were lower in cases versus control subjects (1.0 μg/mL [1.0–1.0] vs 11.7 μg/mL [4.2–27.1]; P < .0001). Interestingly, even within the control group, lower IFX concentrations were associated with subsequent ADAb formation to ADM (P < .01). Before switch from ADM to IFX, median (interquartile range) ADM serum concentrations were lower in cases versus control subjects (1.6 μg/mL [1.6–3.0] vs 9.2 μg/mL [5.7–13.9]; P < .0001). Similarly, even within the control group, lower ADM concentrations were associated with subsequent ADAb formation to IFX (P < .01). Survival analysis showed that an IFX concentration ≤5 μg/mL was significantly associated with subsequent ADAb formation to ADM (P < .0001), whereas an ADM concentration","journal":"Clinical Gastroenterology and Hepatology","year":2021,"id":169013,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.967,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":513245,"name":"María T. Abreu","orcid":"0000-0002-7294-0574","position":1,"is_corresponding":false},{"id":543179,"name":"Sarah N. Flier","orcid":null,"position":2,"is_corresponding":false},{"id":446884,"name":"Konstantinos Papamichael","orcid":"0000-0003-1497-0254","position":3,"is_corresponding":false},{"id":294494,"name":"Florian Rieder","orcid":"0000-0002-9087-1568","position":4,"is_corresponding":false},{"id":250799,"name":"Mark S. Silverberg","orcid":"0000-0002-9534-1419","position":5,"is_corresponding":false},{"id":513510,"name":"Reena Khanna","orcid":"0000-0002-8679-2541","position":6,"is_corresponding":false},{"id":699223,"name":"Lauren Okada","orcid":"0000-0002-5691-3373","position":7,"is_corresponding":false},{"id":699224,"name":"Lei Yang","orcid":"0000-0003-0657-5457","position":8,"is_corresponding":false},{"id":411135,"name":"Anjali Jain","orcid":"0000-0001-5658-367X","position":9,"is_corresponding":false},{"id":446885,"name":"Adam S. Cheifetz","orcid":"0000-0002-6010-1896","position":10,"is_corresponding":false},{"id":325265,"name":"Niels Vande Casteele","orcid":"0000-0003-0854-0274","position":0,"is_corresponding":true}],"reference_count":8,"raw_metadata":null,"created_at":"2026-07-18T23:46:11.334362Z","pmid":"33421628","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}