A40 IBD PATIENTS RECEIVING INFLIXIMAB IN COMBINATION WITH AN IMMUNOMODULATOR ARE LESS LIKELY TO DEVELOP SECONDARY LOSS OF RESPONSE
Bibliographic record
Abstract
Anti-TNF therapy is well established in the treatment of moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC). Therapeutic effect may wane over time leading to secondary loss of response that can be overcome with dose escalation. Data on rate of secondary loss of response is extremely limited. We sought to determine real-world rates of secondary loss of response to anti-TNF therapy in CD and UC and to identify patient and disease factors predictive of loss of response. All 23 prescribers of anti-TNF medications for IBD in Manitoba agreed to participate in the study. Charts of biologic-naive patients started on anti-TNF therapy between 2005 and 2016 were reviewed and demographics, disease characteristics, and IBD treatments recorded. Secondary loss of response was defined by the use of augmented dose anti-TNF therapy after a minimum of 90 days on standard dose anti-TNF. Survival curves were constructed and statistical analysis conducted using Student’s t-test, chi squared test, and log rank test. 670 patients started anti-TNF therapy during the period in question (483 CD, 182 UC, and 5 IBD-U). 233 CD subjects (48.2%) had penetrating disease while 92 UC subjects (50.5%) had pancolitis. Mean age at diagnosis was 29.4 years and 50.0% of subjects were female. Secondary non-responders did not differ from the overall anti-TNF cohort in disease phenotype or demographics. No differences in IBD-related surgeries, hospitalizations, or inflammatory markers prior to initiating anti-TNF therapy were observed. Mean duration of follow up was 32.5 months. Secondary loss of response occurred in 9% of subjects by 6 months, 25% by 12 months, and 39% by 24 months. Thereafter response was durable, with only an additional 4% drop off over five years of treatment. There was a trend toward lower loss of response among infliximab users, but this did not reach the level of significance (p=0.07). Time to loss of response was significantly greater among anti-TNF subjects receiving concomitant immunomodulators (p=0.006). The beneficial effect of combination therapy was limited to infliximab subjects (p=0.0002) with no benefit observed among adalimumab users (p=0.80). Secondary loss of response rate did not differ between CD and UC (p=0.51). Over 40% of IBD subjects treated with anti-TNF therapies ultimately lose response and require dose augmentation, with the majority of cases occurring within the first 24 months. Loss of response is significantly less common among infliximab users receiving concomitant immunomodulators. None
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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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.008 | 0.001 |
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".