Does Measuring Infliximab and Human Anti-Chimeric Antibody Concentrations in Patients With Inflammatory Bowel Disease Impact Clinical Management? A Canadian Experience.
Bibliographic record
Abstract
Background: Infliximab (IFX) is a chimeric (mouse/human) anti-tumor necrosis factor alpha (anti-TNFa) therapy used for treatment of inflammatory bowel disease (IBD). The main phenotypes of IBD are Crohn's disease (CD) and Ulcerative colitis (UC). On biological therapy, patients may become unresponsive to therapy or develop side effects. The reasons for which may be sub-therapeutic drug levels or development of Human Anti-Chimeric Antibodies (HACA). Objective assessment of these two parameters would help guide therapy in some complex patients with IBD. An HACA serum assay is commercially available through Prometheus Laboratories, Inc., San Diego, CA. In Canada, the Ministry of Health and Long Term Care in Ontario (MOHLT) has granted approval for this test, in selected IBD patients, 12 months ago. Methods: We conducted a retrospective chart review of adult patients with IBD in whom HACA and Infliximab trough levels were estimated, to determine whether these results impacted clinical management. The indications for these tests were recorded for each patient. Approval was sought from MOHLT for performing the test. Serum was collected 24 to 48 hours prior to the next infliximab infusion. Results: Thirty-six patients with IBD (29 CD, 7 UC) had HACA and Infliximab levels estimated. The mean age (SD) was 32.5 (13) years and 56% were females. The mean disease duration (SD) was 10(6) years and mean duration on infliximab therapy (SD) was 4(3) years. Indication for testing were diminished response to therapy in 80%, development of side effects in 14% and primary non-response in 6%. HACA was positive in 7 patients and infliximab levels were undetectable in 9 patients. Infliximab levels were undetectable in all patients who were HACA positive except one. Based on these results, treatment was altered in 78% of the patients. Among the 7 HACA positive patients, 3 were switched biological therapy, 2 were switched to immunomodulators (endoscopy showed inactive disease), 2 were continued on infliximab with increased frequency. Among 29 patients who were HACA negative, 9 patients had undetectable drug concentration. In them, frequency of infusion was increased in 6, dose was increased in 2 (10 mg/kg every 4 weeks), and one patient was switched to another biological agent. After modifications in therapy, the drug levels were retested in 4 patients. It was detectable in 3 and undetectable in one who was then referred for surgery. Among the remaining 20 patients with detectable drug levels (>6.25 lg/mL), only limited modifications were required. Of these, 8 were continued on the same treatment, 6 were switched to another biological agent, the infliximab dose was increased in 3, started immunomodulator therapy in 2 and in one patient the dose of infliximab was decreased. Conclusion: Measurement of HACA and infliximab concentration impacts clinical management of patients with IBD. The use of these tests helps tailor therapy and optimizes patient management.
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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 | 0.003 | 0.012 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".