Therapeutic Drug Monitoring of Adalimumab in Patients With Inflammatory Bowel Disease
Bibliographic record
Abstract
The introduction of antitumor necrosis factor (TNF) such as infliximab (IFX) and adalimumab (ADA) has revolutionized the management landscape of inflammatory bowel disease (IBD). However, the response rate to those medications remains sub-optimal with many patients with Crohn’s disease (CD) and ulcerative colitis (UC), showing evidence of primary nonresponse or failing to maintain remission on those medications. One pivotal factor that may play a role in predicting the response to anti-TNF agents is serum drug level. Therapeutic drug monitoring (TDM), defined as the assessment of drug concentrations and antibodies, is an important tool toward optimizing biological therapy.1 TDM can be either reactive, in response to symptoms, signs and/or biomarkers of active disease, or proactive with adjustment of the medication to a target trough level in patients in remission. The DIAMOND study group reported a significant difference in week 26 ADA levels and antibodies between those adults with CD who were in remission at week 52 when compared with those who were not (7.7 ± 3.3 versus 5.4 ± 4.3 Ug/mL: P < 0.001) with less antibodies against ADA in those with higher 6-thioguanine nucleotide (TGN).2 A recent pediatric-randomized study examined the value of proactive versus reactive TDM in a cohort of children and young adults with CD on ADA. Higher corticosteroid-free sustained remission rates were associated with the proactive strategy.3 In a real-world experience, Park et al4 examined the association between ADA trough levels and IBD activity in 236 patients. The study did not find a significant difference between ADA trough levels in patients with active disease versus in those with quiescent disease except for mean tough levels that were significantly higher in patients with a normal CRP compared with those with a high CRP (6.7 ± 6.4 versus 4.7 ± 4.2 mcg/mL; P = 0.023) while the median was not. Nonetheless, there was a significant difference in trough levels between those in endoscopic remission versus those who were not. Higher trough levels were associated with endoscopic and radiological remission. The study was not powered enough to examine the effect of having an immunosuppressive agent on ADA trough levels in those who were on combination therapy versus those who were ADA. On the other hand, TDM was proven effective in guiding clinical management in the majority of patients. The study by Park et al is another step toward confirming the value of reactive TDM in a better guidance of managing patients with IBD. Funding: None. Conflict of Interests: W.E.M. served as an advisory board member for Janssen and AbbVie Canada.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".