P-036 YI Clinical and Serological Factors Associated With Response to Infliximab in Chronic Refractory Pouchitis and Pouch Complications
Bibliographic record
Abstract
Pouchitis refractory to first-line therapies and pouch complications remains problematic following colectomy and ileal-pouch anal anastomosis (IPAA) for ulcerative colitis (UC). Evidence for infliximab (IFX) use in this setting and factors predicting its success remain limited. Here, we investigated IFX use in refractory pouchitis and clinical and serological variables associated with treatment response. Patients were identified from the Mount Sinai Hospital IBD and Pelvic Pouch Databases, Toronto, Canada. Clinical, endoscopic and serological data were reviewed from 579 individuals who underwent colectomy and IPAA from 2000 to 2014. Patients with chronic refractory pouchitis and Crohn’s Disease- like outcome treated with IFX were included. Pretreatment parameters were measured within 4 weeks of induction and IFX response at a median of 9 (initial) and 48 weeks (sustained) respectively. Complete response was defined as symptomatic and endoscopic resolution with modified Pouchitis Disease Activity Index (mPDAI) score <5. Partial response was defined as improvement in symptoms with reduction in mPDAI >2. Endoscopic mucosal healing, pouch excision, pouch complications and CRP were recorded. Serum was analyzed for antibodies against Saccharomyces cerevisiae (ASCA), OmpC, CBir1 and perinuclear neutrophil cytoplasm (pANCA). Fisher’s exact testing and Kruskal-Wallis detected differences in clinical and serological variables between subgroups. Logistic regression models were applied to estimate odds ratio (OR) and 95% confidence interval (CI) of clinical and serological factors with initial and sustained clinical response as dependent variables. Results were deemed significant if P-value was ≤0.05. Thirty-one patients were included (33% male; age 32.6 ± 2.6 [mean ± SE]). 26% were on combined therapy with immune-modulator. Seventy-four present achieved post-induction response at median 9 weeks (IQR [6.5–13]) (48% complete, with concomitant mucosal healing). At median 48 weeks (IQR [25–71.5]), 62.6% retained response (29.6% complete). There were significant reductions in mPDAI in the entire cohort from a pre-induction score of 8.5 ± 0.3 to 2 ± 3.4 at final follow-up (mean, SE; P < 0.002) and in CRP from 29.48 ± 6.2 mg/L to 5.76 ± 1.6 mg/L (P < 0.001). Age, gender, smoking, pre-pouch disease extent and CRP did not affect response to IFX. Pretreatment mPDAI score did not significantly affect sustained IFX response but higher pretreatment mPDAI scores were negatively associated with early mucosal healing (P = 0.056; OR = 0.5, 95% CI, [0.2–1.010]). Patients with pretreatment mPDAI >10 were less likely to have initial mucosal healing (P = 0.03). Initial mucosal healing was associated with sustained complete response (P < 0.05; [OR] = 13.2; 95% confidence interval [CI], 1.0–165). Presence of ASCA was associated with higher initial mPDAI (P = 0.016), but no difference in treatment response. IFX responders had a lower number of positive antibody titers (2 positive titers versus 3, mean; P < 0.05). Having >2 positive titers was associated with longer term non-response to IFX though not significantly. IFX was effective in the short- and longer term in patients with chronic refractory pouchitis and pouch complications. Mucosal healing after induction is the strongest clinical association with a complete sustained response to IFX in this group and pretreatment mPDAI may help predict this.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 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".