Allopurinol in combination with thiopurine induces mucosal healing and improves clinical and metabolic outcomes in IBD
Bibliographic record
Abstract
Background: Thiopurines, azathioprine (AZA) and 6-mercaptopurine (6-MP) are common maintenance medications for inflammatory bowel disease (IBD). Excessive methylation via thiopurine methyltransferase (TPMT) frequently causes therapeutic failure. Allopurinol reduces excessive 6-methyl-mercaptopurine (6-MMP) while enhancing 6-thioguanine (6-TGN) levels. The aim of this study was to evaluate clinical, metabolic and endoscopic impact of allopurinol in combination with low-dose thiopurine in IBD. Methods: Retrospective review of consecutive cases treated with allopurinol. Metabolites and their ratios (6-MMP/6-TGN) were compared pre- and post-allopurinol. Clinical and endoscopic remission were assessed. Results: Allopurinol ( n = 66) reduced mean dose of AZA by 70% ( p < 0.01). Baseline levels (SD) 6-TGN, 6-MMP and 6-MMP/6-TGN were 165 (64), 9388 (5234) and 59.8 (30.3), respectively. These values improved on allopurinol to 297 (102), 896 (1031) and 3.4 (4.0), respectively ( p < 0.0001). Therapeutic 6-TGN level (>235) was achieved in 49/58 cases on allopurinol combination therapy, versus 9/58 monotherapy ( p = 0.0001). Among the thiopurine failure group (40 patients), clinical remission or response was observed in 65% and 22% of patients, respectively. In the asymptomatic group with excessive 6-MMP, 11/14 achieved sustained remission on allopurinol. Repeat colonoscopy ( n = 28) showed mostly endoscopic remission (67.9%) or improvement (17.8%). Few had unimproved lesions (14.3%). Importantly, 46% of cases had complete mucosal healing. Two patients had cancer on combination therapy (de novo pancreatic cancer and fatal recurrence of metastatic testicular cancer). Elevated transaminases were reduced on allopurinol (48.2 versus 6.9%) ( p < 0.001); no change in leukopenic or infectious events occurred. Conclusion: Allopurinol in combination with low-dose thiopurine corrected excessive 6-MMP levels, resulting in clinical remission and mucosal healing in the majority of cases. The potential cancer risk of allopurinol and thiopurine combination therapy needs further research.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".