Association Between Serum Concentration of Infliximab and Efficacy in Adult Patients With Ulcerative Colitis
Bibliographic record
Abstract
Background & AimsWe analyzed data collected during the Active Ulcerative Colitis Trials (ACT-1 and ACT-2) to assess relationships between serum concentrations of infliximab and outcomes of adults with moderate-to-severe ulcerative colitis.MethodsWe compared serum concentrations of infliximab with outcomes of 728 patients with moderately-to-severely active ulcerative colitis who participated in ACT-1 or ACT-2; efficacy data were collected at weeks 8, 30, and 54 (for ACT-1 only). Relationships between serum concentration of infliximab and efficacy outcomes were assessed using trend, logistic regression, and receiver operating characteristic curve analyses. We also evaluated factors that affected the relationship between exposure and response.ResultsMedian serum concentrations of infliximab at weeks 8, 30, and/or 54 were significantly higher in patients with clinical response, mucosal healing, and/or clinical remission than in patients who did not meet these response criteria. There were statistically significant relationships between quartile of infliximab serum concentration and efficacy at these time points (P < .01). Infliximab therapy was effective for a smaller proportion of patients in the lowest quartile, and these patients had lower serum levels of albumin and a higher incidence of antibodies to infliximab than patients in other quartiles. Although the relationship between exposure to infliximab and response varied among patients, approximate serum concentrations of 41 μg/mL infliximab at week 8 of induction therapy and 3.7 μg/mL at steady-state during maintenance therapy produced optimal outcomes in patients.ConclusionsSerum concentrations of infliximab are associated with efficacy in patients with moderate-to-severe ulcerative colitis; however, complex factors determine the relationship between exposure to this drug and response. A prospective evaluation of the value of measuring serum concentrations of infliximab should be performed before these data can be included in patient management strategies. Clinicaltrials.gov numbers: NCT00036439 and NCT00096655. We analyzed data collected during the Active Ulcerative Colitis Trials (ACT-1 and ACT-2) to assess relationships between serum concentrations of infliximab and outcomes of adults with moderate-to-severe ulcerative colitis. We compared serum concentrations of infliximab with outcomes of 728 patients with moderately-to-severely active ulcerative colitis who participated in ACT-1 or ACT-2; efficacy data were collected at weeks 8, 30, and 54 (for ACT-1 only). Relationships between serum concentration of infliximab and efficacy outcomes were assessed using trend, logistic regression, and receiver operating characteristic curve analyses. We also evaluated factors that affected the relationship between exposure and response. Median serum concentrations of infliximab at weeks 8, 30, and/or 54 were significantly higher in patients with clinical response, mucosal healing, and/or clinical remission than in patients who did not meet these response criteria. There were statistically significant relationships between quartile of infliximab serum concentration and efficacy at these time points (P < .01). Infliximab therapy was effective for a smaller proportion of patients in the lowest quartile, and these patients had lower serum levels of albumin and a higher incidence of antibodies to infliximab than patients in other quartiles. Although the relationship between exposure to infliximab and response varied among patients, approximate serum concentrations of 41 μg/mL infliximab at week 8 of induction therapy and 3.7 μg/mL at steady-state during maintenance therapy produced optimal outcomes in patients. Serum concentrations of infliximab are associated with efficacy in patients with moderate-to-severe ulcerative colitis; however, complex factors determine the relationship between exposure to this drug and response. A prospective evaluation of the value of measuring serum concentrations of infliximab should be performed before these data can be included in patient management strategies. Clinicaltrials.gov numbers: NCT00036439 and NCT00096655.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".