Effectiveness and Safety of Advanced Combination Treatment in Patients With Refractory Inflammatory Bowel Disease or Concomitant Immune-Mediated Disease or Extraintestinal Manifestations: A Multicenter Canadian Study
Bibliographic record
Abstract
INTRODUCTION: Owing to the therapeutic ceiling associated with inflammatory bowel disease (IBD) therapies, some patients may require 2 advanced therapeutic agents, known as advanced combination treatment (ACT) to control disease or treat associated extraintestinal manifestations (EIMs). METHODS: We included adult patients with IBD from 9 Canadian centers treated with either 2 biological therapies, a biological plus an oral small molecule, or 2 small molecules. Indications for ACT were the following: (i) refractory IBD, (ii) uncontrolled immune mediated diseases, and (iii) uncontrolled EIMs. Primary outcomes were cumulative rates of clinical and endoscopic response and remission at 6 and 12 months. Secondary outcomes included serious adverse events and infections. Cox-proportional hazard analyses identified independent predictors of treatment effectiveness. RESULTS: We included 105 IBD patients (76 Crohn's disease, 29 ulcerative colitis) with median age 35 years (Interquartile Range 35.4-40.8). At baseline, 39% had perianal involvement, 58% had failed at least 3 advanced therapies, and 40% had previous surgery. The primary reason for ACT was refractory IBD (63.8%), with the add-on approach used in 97.1% cases. The most frequent combination was antitumor necrosis factor + anti-integrin. At 12 months, cumulative rates of clinical and endoscopic response were 60.0% and 32.4%, respectively, and remission rates were 29.5% and 28.6%. Perianal disease was associated with reduced clinical remission (hazard ratio [HR] = 0.33, 95% confidence interval [CI]: 0.17-0.65, P = 0.001) and endoscopic response (HR = 0.42, 95% CI: 0.12-0.50, P = 0.001). Longer disease duration (HR = 0.96, 95% CI: 0.92-0.99, P = 0.035) and baseline steroid use (HR = 0.39, P = 0.006) was associated with reduced clinical remission. Serious adverse events and infections occurred in 12.4% and 7.6% of patients, respectively. DISCUSSION: ACT was effective in achieving clinical and endoscopic outcomes in patients with refractory IBD or concomitant immune-mediated diseases/EIMs, with favorable safety profile.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 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".