Loss of Efficacy to Anti-TNF Therapy in the Management of Crohnʼs Disease: A Brazilian Multicenter Observational Study
Bibliographic record
Abstract
Besides the great benefit of anti-TNF agents in the management of Crohn's disease (CD), it is known that efficacy of both Infliximab (IFX) and Adalimumab (ADA) can be reduced over time. Loss of response to these agents can be explained by immunological issues, such as antibody formation or even lower trough levels of the drugs. There is lack of real life data in Latin American CD patients regarding the issue of loss of efficacy (LOE) to anti-TNF therapy. The primary objective of this study was to analyze the incidence of LOE to both IFX and ADA in a cohort of Brazilian CD patients. The secondary objectives were to define the timing of LOE to the drugs and to identify possible risk factors for its appearance. This was a retrospective, observational cohort study, with CD patients treated with anti-TNF therapy from 5 referral IBD centres from Brazil. Inclusion criteria: CD patients, responders to the first biological agent (anti-TNF naive) with completed induction regimen. Exclusion criteria: undetermined IBD, primary non-responders and patients previously exposed to anti-TNF agents. Patients were allocated in two groups, regarding the drug administered (IFX or ADA). Electronic chart review was performed and a specific protocol was ful-filled. Variables analyzed: demographic data, Montreal classification, concomitant medications, smoking, perianal CD, time of follow-up, presence of LOE, timing and the reasons for its occurrence. LOE was defined as one of the following characteristics: need for steroids, occurrence of abdominal surgery during treatment, dose increase, interval shortening or switching of the anti-TNF agent. Statistical analysis was performed with student's t test, Mann Whitney, Fischer or chi-square tests to demonstrate comparability of the groups. Log-rank test (Kaplan Meier) was performed to analyze the timing of loss of efficacy. Cox regression multivariate analysis was also performed to define risk factors, with P < 0.05 considered significant. A total of 175 patients were included in the study (117 in the IFX and 58 in the ADA group). The groups were considered homogeneous regarding demographic data, Montreal classification, smoking status and perianal CD. There were more patients exposed to steroids and azathioprine in the IFX group. Medium follow-up period was 17.3 (±12.4) months on the IFX and 13.1 (±11.3) months on the ADA group. Overall, LOE occurred in 47/117 (40.2%) of the IFX and in 9/58 (15.5%) ADA patients (P = 0.001). Medium timing for LOE was 11.8 (±8.1) months on IFX and 13.3 (±12.3) months on ADA patients (P = 0.073), without significant difference on the reasons for its occurrence (P = 0.125). On multivariate analysis, younger patients (Montreal A1) were at risk for LOE (P = 0.032). On COX regression analysis, a higher risk for LOE was noticed when IFX was administered (OR = 3.33; P = 0.006) and in patients with perianal CD (OR = 2.23; P = 0.026). Loss of efficacy (LOE) was observed in 40.2% of the IFX and in 15.5% of the ADA patients, without any significant difference in timing and reasons for its occurrence. These data were similar to the literature of other countries. The risk for the development of LOE was higher in younger patients, on IFX therapy and with perianal CD.
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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 | 0.002 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| 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".