The Association Between 6-Thioguanine Nucleotide Levels, Adalimumab Exposure, Immune Response, and Drug Clearance
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ID: 317402
2026
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Abstract
Abstract Background Thiopurines are associated with improved infliximab pharmacokinetics (PK), but their impact on adalimumab PK and immunogenicity is not well defined. This study examined associations between 6-thioguanine (6-TGN) levels and antibodies to adalimumab (ATA), adalimumab drug levels (ADL), and adalimumab clearance (CL). Methods Using a large clinical laboratory database, we included adults with Crohn’s disease or ulcerative colitis treated with thiopurines and adalimumab who had RBC 6-TGN and adalimumab concentrations measured within 30 days. ATA, ADL, and CL were assessed using drug-tolerant assays and nonlinear mixed-effects modeling. A 6-TGN threshold of ≥ 125 pmol/8 × 108 RBCs was used. Logistic regression was performed to calculate odds ratios (ORs). Results We analyzed 1,194 specimens from 1,100 patients; ATA positivity was 3.7%. Compared with 6-TGN ≥125 pmol/8 × 108 RBCs, lower 6-TGN was associated with higher odds of ATA formation (>1.7 U/mL; OR = 2.55), lower odds of ADL ≥10 µg/mL (OR = 0.58), and lower odds of low CL (< 0.318 L/day; OR = 0.55). Compared with every-other-week dosing, weekly dosing produced higher ADL (13.1 vs 8.9 µg/mL; p < 0.01) but also higher CL (0.425 vs 0.302 L/day; p < 0.01). Within each dosing interval, higher 6-TGN levels were associated with lower prevalence of ATA (p < 0.05) and a higher chance of achieving ADL ≥10 µg/mL (p < 0.01) and CL < 0.318 L/day (p < 0.01). Conclusion Higher 6-TGN levels are associated with reduced immunogenicity, higher adalimumab drug levels, and lower clearance. Thiopurine may enhance adalimumab PK and support more favorable therapeutic response.
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| Authors | Andres Yarur, Jonathan C Lo, Bincy Abraham, Stephen Hanauer, Thierry Dervieux |
| Journal | Crohn s & Colitis 360 |
| Year | 2026 |
| DOI |
10.1093/crocol/otag053
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| URL | |
| Keywords | Keywords not found |
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