P542 Infliximab salvage therapy in acute severe ulcerative colitis: A systematic review and meta-analysis
Bibliographic record
Abstract
Thirty percent of patients with acute severe ulcerative colitis (ASUC) require emergency colectomy within 3 months of admission. Infliximab (IFX) is effective as salvage therapy and recent data on IFX pharmacokinetics suggest that dose intensification schedules (DIS) beyond standard induction schedules (SIS) may be of benefit. However, data supporting DIS therapy are conflicting and the optimal IFX dosing strategy is unknown. We performed a systematic review and meta-analysis to examine the impact of IFX dose number and intensification on colectomy free survival (CFS) in ASUC. MEDLINE, PubMed, and EMBASE were searched from January 2000 to September 2017 to identify studies reporting outcomes of hospitalised steroid refractory ASUC treated with IFX salvage. CFS was examined for: all pooled patients; 5 mg/kg single dose vs. 5 mg/kg multiple dose induction, and; SIS (5 mg/kg at 0, 2, and 6 weeks) vs. DIS (multiple 10 mg/kg or 5 mg/kg using accelerated schedules). Thirty-nine studies (n = 1827 patients) were included in this analysis. 11 contained comparative data and 28 had non-comparative data. Pooled CFS with IFX salvage was 84.0% (95%Cl 81.9–86.0%) at 1 month, 79.8% (77.7–81.8%) at 3 months and 70.5% (68.1–72.8%) at 12 months. Multiple dose induction (5 mg/kg) was superior to single dose (5 mg/kg) induction with respect to CFS at 1 and 3 months but not 12 months [odds ratio (OR) 8.86 (95% CI 1.04–75.8), I2 = 0%, p = 0.05, n = 127; OR 4.31 (2.46–7.56), I2 = 0%, p < 0.001, n = 421, and; OR 2.02 (0.81–5.01), I2 = 0%, p = 0.13, n = 127, respectively]. DIS was not found to be superior to SIS for CFS at 1, 3, or 12 months in five evaluable studies (n = 337) [OR 0.59 (0.17–2.04), I2 = 52%, p = 0.41; OR 0.64 (0.27–1.50), I2 = 43%, p = 0.31, and; OR 0.73 (0.39–1.35), I2 = 20%, p = 0.53, favouring standard induction]. DIS was utilised in patients who had a significantly higher mean CRP compared with SIS [mean difference 14.31mg/l (0.35–28.32), p = 0.04] as well as significantly lower serum albumin [mean difference 2.75g/l (1.26–4.23), p < 0.001]. There was no significant difference in age, disease duration or IV steroid duration. There are few high-quality studies available to guide the use of IFX in ASUC. Whilst multiple 5 mg/kg doses appear superior to single 5 mg/kg dose rescue therapy, dose intensification (with high dose or accelerated strategies) was not superior to standard induction in this analysis. However, dose intensification was utilised in patient groups with adverse biochemical profiles known to be associated with increased colectomy risk, thus the finding may be confounded. Controlled interventional studies are therefore required to investigate whether IFX dose intensification is able to mitigate the risk of colectomy.
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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 | 0.009 | 0.020 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.018 | 0.035 |
| Bibliometrics | 0.006 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 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".